Antimicrobial Resistance Benchmark 2021

Antimicrobial Resistance
Benchmark 2021

1

Antimicrobial Resistance Benchmark 2021

ACKNOWLEDGEMENTS
The Access to Medicine Foundation would like to thank thefollowing people and organisations for their contributions tothis report.1
FUNDERSUK Foreign, Commonwealth and Development Office
The Dutch Ministry of Health, Welfare and SportAXA Investment Managers
Wellcome TrustExpert Review Committee

Research Team

Reviewers

Hans Hogerzeil - Chair

Fatema Rafiqi

Brenda Waning

Gregory FrankElisabetta Cesari

Brian Kaiser

Joakim Larsson

Diane Dinar-Farjon

Christine Årdal

Marc Mendelson

Martijn van Gerven

Francesca Chiara

Maria Larrson Ortino

Moska Hellamand

Joakim Larsson

Mirfin Mpundu

Teresa Sánchez Pascua

Kevin Outterson

Sudarshan Jain

Marc Mendelson

Sarah Paulin (Observer)

Mirfin Mpundu
Editorial TeamAnna Massey

ACCESS TO MEDICINE FOUNDATION

Eleanor Bley Griffiths

The Access to Medicine Foundation is an independent

Rachel Jones

non-profit organisation based in the Netherlands. It aims
to advance access to medicine in low- and middle-income

Additional contributors

countries by stimulating and guiding the pharmaceutical

Dulce Calçada

industry to play a greater role in improving access toGuilherme Ferreira

medicine.

Address

Contact

Naritaweg 227-A

For more information about this publication, please contact

1043 CB, Amsterdam

Fatema Rafiqi, Research Programme Manager

The Netherlands

frafiqi@accesstomedicinefoundation.org+31 (0) 20 215 35 35
www.amrbenchmark.org

1 This acknowledgement is not intended to imply thatthe individuals and institutions referred to above endorse
the Antimicrobial Resistance Benchmark methodology,
analyses or results. Decisions regarding the final analysis were ultimately made by the Access to Medicine
Foundation.

About the cover: On the cover is a young
boy from Tanzania, a country where resistant bacteria is widespread as are many
issues related to access and stewardship.
Photo: Jasmin Merdan (Getty Images)2

Antimicrobial Resistance Benchmark 2021

Progress against
drug resistance must
accelerate

For the last five years, we have been tracking how the biggest

Antimicrobial resistance is not a problem for the future. It ispharmaceutical companies in the antibiotic market have tack-here already, with an estimated 750,000 people dying eachled the rise of antimicrobial resistance (AMR) and the global

year from drug-resistant infections. At the same time, 5.7

need for appropriate access to antimicrobials. This third

million people also die annually from treatable infections

Antimicrobial Resistance Benchmark has identified progressbecause they lack access to medicines. The combination of

in some areas, including a significant increase in forward plan-

more superbugs and inadequate treatment is brewing up aning to make new medicines available in low- and middle-in-lethal cocktail that threatens to unleash spiralling levels ofcome countries.

drug resistance, driven by natural selection.

That is the good news. The bad is news that there is still a

We know what needs to be done to counter this threat.

widespread failure to get established antibiotics to patients in

There are tried-and-tested tools that can increase local availa-

resource-poor settings, where the risk of drug-resistant infec-

bility of vital antibiotics in poorer nations, such as wider prod-tions is greatest. Just one third of the products we examined

uct registration, technology transfers and strong, long-last-

had any kind of strategy in place to address access – suching partnerships. All these things have been shown to improveas price adjustments to make medicines more affordable, oraccess by pooling the resources across a fragile healthcare

licensing agreements to boost supply. This lack of appropriate

ecosystem.

access forces doctors to use suboptimal treatments, giving

Back in January 2016, more than 100 companies and trade

pathogens further opportunities to develop resistance andorganisations came together to sign the Davos Declaration,

thereby stoking the rise of resistance.

committing to developing better ways to provide dependa-

When it comes to R&D, Big Pharma’s engagement appears

ble and sustainable supplies of antibiotics, and urging govern-

to have stabilised after years of retrenchment – yet the pipe-

ments to work with them. Since then, there have clearly beenline of new products remains thin, and progress is heavily reli-

moves in the right direction. Companies and their partners

ant on a few large companies, as well as the many small bio-must now turn these tentative steps into ambitions strides intechnology firms with precarious finances. Generic medi-order to get ahead of the rising tide of drug resistance before

cine manufacturers are making further advances in steward-

it is too late.

ship, including several large Indian players that have stayedfocused on AMR despite the ravages of COVID-19 in theirhome country.
What is needed now is a greater sense of urgency from all
players. We must learn the lessons from the coronavirus pandemic. The unacceptable inequity in global access to COVID19 vaccines must not be repeated when it comes to defending
all communities against superbugs.

Jayasree K. Iyer
Executive Director
Access to Medicine Foundation

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Antimicrobial Resistance Benchmark 2021

Table of contents
6

EXECUTIVE SUMMARY

92

B EST PR ACTI CES

93

Research & development96

Responsible manufacturing

11

BENCHMARK PERFORMANCE

11

Antimicrobial Resistance Benchmark - 2021

97

Appropriate access

14

How the large research-based companies perform

100

Stewardship16

How the generic medicine manufacturers perform
105

RE PO RT CARDS18

KEY FINDINGS

106

GlaxoSmithKline plc

18

Pharma companies make limited use of the many

110

Johnson & Johnson

ways to improve access to antibiotics

114

Merck & Co, Inc (MSD)

Progress on limiting release of antibiotic waste into

118

Novartis AG

environment, but gaps remain

122

Otsuka Pharmaceutical Co, Ltd

Increased access and stewardship planning in R&D is126

Pfizer Inc

hopeful sign for poorer countries

130

Sanofi

134

Shionogi & Co, Ltd138

Abbott Laboratories

141

Alkem Laboratories Ltd

20
22

25

RESEARCH AREAS

27

RESEARCH & DEVELOPMENT

144

Aurobindo Pharma Ltd

29

Company involvement in R&D

147

Cipla Ltd

30

Which pathogens are receiving most attention?

150

Fresenius Kabi AG

33

Changes in the pipeline since 2020

153

Hainan Hailing Chemipharma Corp Ltd

34

New medicines in the pipeline

156

Sun Pharmaceutical Industries Ltd

35

Approvals

159

Teva Pharmaceutical Industries Ltd

36

Stewardship & access plans

162

Viatris Inc

40

Looking ahead
165

APPE N D ICES43RESPONSIBLE MANUFACTURING

166

Appendix I: Analysis, scoring and review process

45

Environmental risk-management strategies

169

Appendix II: Limitations

47

Setting discharge limits

170

Appendix III: Scoring guidelines

48

Compliance with limits:

177

Appendix IV: Identifying best practices

50

Transparency from companies

178

Appendix V: Priority pathogens included

51

Antifungals

52

Looking ahead

for analysis in R&D
179

Appendix VI: Access countries

180

Appendix VII: Appropriate Access:181

Appendix VIII: Guide to Report Cards

55

APPROPRIATE ACCESS

57

Registration of products

63

Access strategies

185

Appendix IX: Figures

67

Case studies

186

Appendix X: Definitions

70

Continuous supply

72

Technology transfers

74

Looking ahead

76

STEWARDSHIP

78

Surveillance programmes

83

Sales practices

86

COI mitigation in education programmes

88

Brochure and packaging adaptations

90

Looking ahead

Product scope and definitions

4

Antimicrobial Resistance Benchmark 2021

About this report

The 2021 Antimicrobial Resistance Benchmark, which iswere asked to provide information about factories involved

published by the Access to Medicine Foundation, takes anin the manufacture of their antibacterial products, with morein-depth look at how the pharmaceutical industry is respond-

than a thousand sites reported.

ing to the challenge of drug-resistant infections. It exam-

To assess ‘appropriate access’, the Benchmark looks at allines the behaviour of 17 companies with a major stake in theof the companies’ actions to improve access to their antimi-

anti-infectives space: eight large research-based pharmaceu-

crobial products in 102 low- and middle-income countries

tical companies and nine generic medicine manufacturers.

(LMICs). This analysis focuses only on those companies’ prod-

These companies are evaluated in areas where they haveucts which either a) are patented, thus conferring a domi-

the greatest opportunity and responsibility to limit antimicro-

nant market position, or b) are off-patent generic medicines

bial resistance (AMR); specifically, research and developmentwith large sales volumes, and are also designated as ‘essential’(R&D), managing antibacterial manufacturing waste, andfor good functioning health systems by WHO. There are 166

ensuring appropriate access to – and responsible stewardshipproducts under analysis.

of – antimicrobial medicines and vaccines.
This is the third iteration of the Benchmark, following

Finally, all companies are also assessed on their global
stewardship policies practices.

on from previous reports published in 2018 and 2020. By
highlighting where effective action is already being taken,

H OW CO M PAN I ES AR E SCO R E D

and by showing where not enough is yet being done, theEach of the 17 pharmaceutical companies has been given both

Benchmark’s data and analysis can be used as a tool to guidea score and a ‘Report Card’, detailing their performance sinceand stimulate pharma companies to tackle AMR.

the previous Benchmark and outlining specific opportunities
for improvement.
Scoring in the 2021 Benchmark is based on a framework of

WHAT WE M E A SU R E

To assess R&D, the Benchmark focuses in on the eight large

20 indicators, which are organised into three Research Areas:

research-based companies and their projects that target the

Research & Development; Responsible Manufacturing; andpathogens that pose the highest risk of drug resistance, as

Appropriate Access and Stewardship. The Benchmark takes aidentified by the US Centers for Disease Control (CDC) andqualitative and quantitative approach to the data, examining

the World Health Organization (WHO).

and verifying information provided by the companies in order

In terms of responsible manufacturing, all 17 companies

to reach fair conclusions about their performance.

SECTI O NS I N TH IS RE PORT
Benchmark performance

Key findings

Research areas and best practiceCompany Report Cards

An analysis of how the 17

The three most notable findings

Four chapters providing in-depth

Set of 17 Report Cards setting out

companies compare, revealingfrom the 2021 Benchmark’s

information about the companies’

in detail how each of thewhich companies lead in the

research. These cover crucial

actions in each area, and analysing

companies has performed, their

Benchmark and why. Large

topics: R&D, access to vaccines andwhat the data shows about theofficial score, and what tangible

research-based companies andmedicines in poorer countries, andpharmaceutical industry. Examples

steps they could take to combat

generic medicine manufacturers

safe disposal of antibacterialof best practice are featured in

antimicrobial resistance in future.

each come under the spotlight.

manufacturing waste.

order to show what can be done.

5Antimicrobial Resistance Benchmark 2021

Executive Summary

The 2021 Antimicrobial Resistance Benchmark evaluates how 17 of the world’s largest pharmaceutical companies are performing in the fight against antimicrobial resistance (AMR).
These are the companies with the greatest capacity and opportunity to curb AMR, and theBenchmark examines their actions in multiple areas in order to provide a comprehensive
picture of what is – and what is not – being done. Many of the companies, consisting of eightlarge research-based companies and nine generic medicine manufacturers, have moved
slowly in the right direction since the previous Benchmark report was published in 2020,
despite the ongoing COVID-19 pandemic. But while progress can be seen on some fronts,
the Benchmark also identifies concerning gaps in performance.
Why this matters
AMR is a quietly growing, yet deadly, threat. An estimated 750,000 people already die eachyear due to drug-resistant infections, and unless urgent action is taken, this number will
surge over the coming years. Resistance to even ‘reserve’ antibiotics has increased: 50-70%
of the common Gram-negative isolates are now multidrug resistant. At the same time, 5.7
million people die each year from treatable infections due to a lack of access to medicine,compounding the problem as pathogens are given more of a chance to develop resistance.
Antibiotics and other antimicrobials are essential for combatting infectious diseases
across the world; if these drugs become ineffective due to resistance – and if replacement drugs are not developed and approved – then the effects on public health will besevere. With the world’s attention rightly focused on COVID-19, resistant pathogens continue
to emerge and proliferate. The impact of the pandemic on resistance rates is estimated to beconsiderable, driven by the routine use of antibiotics without appropriate diagnosis in patients
hospitalised with COVID-19, and by global disruptions to antibacterial vaccination campaigns.
This ‘silent pandemic’ can be brought to a halt, and the pharmaceutical industry has a central role to play. The Benchmark tracks, stimulates and guides positive action by highlighting
where steps are already being taken, where companies can do better, and where the ecosystem of incentives can be further strengthened.
Analysis of industry trends
The Benchmark finds that, while the pipeline of new antibacterials and antifungals remains
small, engagement by many large research-based companies’ with antimicrobial R&D appears
to be growing modestly rather than continuing to shrink. These companies are also improving
their forward planning for late-stage medicine and vaccine projects, both in terms of how they
will provide access to those products in low- and middle-income countries (LMICs), and how
they will safeguard the new products’ effectiveness via stewardship strategies.
However, among the 17 companies in scope, there is a lack of momentum in providing
access to existing antibiotics and other antimicrobial products in LMICs, where the risk ofdrug-resistant infections is generally highest. There are many strategies available to pharmacompanies to improve access to their products in poorer countries, such as tiered pricing, or
measures to ensure continuous supply. But as things stand, most access strategies are notbeing widely used, or remain focused on a small set of countries, people, and diseases.
On the manufacturing side, the Benchmark finds that pharmaceutical companies are

6Antimicrobial Resistance Benchmark 2021

ANTI M I CRO B IAL RESISTANCE B E NCH MARK – 2021

Large research-based companies

FI GU R E 1

Generic medicine manufacturers

100%

60%

50%

15%

bin
d
Ab o
bo
tt
Fre
Via
se
t
niu ris
sK
ab
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Cip
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Su
n P eva
ha
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a
Alk
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ina
em
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ail
ing

0%

Au
ro

0%

● Performance in 2021 ● Room to improve

Jo

hn

so
n

GS
K
Pfi
ze
&J
r
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ns
o
n
No
va
rti
s
Sa
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Sh ofi
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og
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MS
D

20%

46%

47%

63%

67%

60%

50%

69%

71%
57%

60%

58%

63%

68%

81%

84%

100%

making greater efforts to curb the release of wastewater containing active pharmaceutical ingredients (APIs) into local waterways, including by setting and enforcing discharge limits
with their third-party suppliers. This is an encouraging step, even though few of their suppliers’
factories are – as yet – reported as being compliant with those limits.
Stewardship practices are also improving gradually in multiple areas, such as in sales practices for antimicrobial products, where the first three generic medicine manufacturers havetaken steps towards decoupling sales volumes from financial incentives from sales agents.
Which companies are the leaders in 2021?
GSK and Pfizer are joint leaders among the large research-based companies evaluated. GSK
has the largest R&D pipeline of any of the companies evaluated, and also performs well inenforcing discharge limits along the manufacturing supply chain. Pfizer has made the biggest
strides since the previous Benchmark in the scale and scope of its approach to AMR, including
by boosting its infectious diseases R&D, and by demonstrating best practice in multiple areas.
Aurobindo, Abbott and Viatris are the leaders among the generic medicine manufacturers,
taking steps to combat overselling of antimicrobials. Abbott and Viatris, alongside Cipla, arealso the first of this group of companies to report setting discharge limits at their third-party
suppliers’ manufacturing sites. Overall, progress by the generic medicine manufacturers canbe seen in transparency, stewardship, sales practices, and wider registration of medicines in
LMICs.

7

Antimicrobial Resistance Benchmark 2021

FI N D I NGS I N B RI E F• Only one third (54) of the pharma companies’ 166 antibacterial and antifungal products inscope are covered by any ‘access strategy’ in any of the 102 low- and middle-income countries where better access to antimicrobial products is most urgently needed.
• Some pharma companies are taking tangible actions to improve access to specific products and boost local supply – for example via technology transfers to manufacturing sites incountries including Pakistan, Brazil and Nigeria.
• More pharma companies report that they require third-party suppliers to set discharge limits
at their manufacturing sites, but only 5.2% of suppliers’ sites are reported as being compliant
with these limits. The figure is ten times higher at the companies’ directly-operated sites.
• Among the eight large research-based companies, the Benchmark identified 92 R&D projects that target infections caused by ‘priority pathogens’ – those bacteria and fungi posing
the highest risk to human health due to drug resistance. This is a modest increase on 2020,
when the same eight companies were developing a combined 77 projects, but the pipeline
remains small.
• 18 out of 20 late-stage medicine projects in this analysis have both access and stewardshipplans in place, and all 11 late-stage vaccine projects have access plans. There has been sustained progress in this area since the first Benchmark.
• The Benchmark previously reported an increase in the number of pharmaceutical companies
that had stopped the use of sales agents altogether, or had decoupled agents’ bonuses fromsales volume. In 2021, three more generic medicine manufacturers took action to combat
overselling: Abbott, Aurobindo and Viatris.
LOO KI NG AH E AD
Even amidst the ongoing COVID-19 pandemic, the pharmaceutical industry has managed todeliver progress against AMR. One lesson to be learnt from the diverse failures and successes
in the fight against COVID-19 is that such a complex global issue can only be tackled throughcollaborative, coordinated action. With tried and tested policies and practices in the playbook,the pharmaceutical industry must now accelerate its efforts against this global health security
threat, with support from policymakers and investors, and through partnerships.
• In R&D, the unwavering priority is for companies to deepen their investment and engagement in antibacterial and antifungal R&D, with a focus on pathogens in the highest threat
categories, and to further tailor the detail and specificity of stewardship and access plans.
• In terms of manufacturing, companies must continue to follow through on commitments togood practices, including by extending standards to API and drug-product suppliers. Sharing
data on water flows and concentrations will help accelerate the uptake of good practice.
• To deliver appropriate access to life-saving medicines and vaccines, the industry has twocore priorities: establish a continuous and local supply of high-quality medicines, and todevelop and implement tailored strategies for access to specific products for underserved
populations in a wider range of low- and middle-income countries.
• In terms of stewardship, to avoid overuse and misuse of antimicrobial medicines, pharmacompanies are strongly encouraged to fully and consistently decouple incentives for sales
agents from sales volumes, either by avoiding the use of sales agents altogether, or byremoving the financial incentive linked to sales volumes. This practice has been pioneered
for anti-tuberculosis medicines, and can be successfully transferred.

8

©GSK

©GSK
©Viatris©Pfizer©Sanofi©Shionogi

Antimicrobial Resistance Benchmark 2021

Top: Sanofi is running tech transfers. GSK adapts packaging to support responsible use. GSK leads in R&D.
Bottom: Anti-TB medicines are not promoted by sales
staff. Viatris leads in access strategies for TB medicines.
Pfizer shares raw surveillance data.

B EST PR ACTICES AT A G L ANCEThe 2021 Antimicrobial Resistance Benchmark identified best practices in each of its three
Research Areas. In the coming months, the Access to Medicine Foundation will work to accelerate their uptake by other pharmaceutical companies, to help raise the level of standardpractice.
• GSK shows best practice in antibacterial and antifungal R&D, with the largest pipeline ofprojects that target priority pathogens, including those in the highest threat categories.
• Pfizer makes strategic investment in antibacterial and antifungal R&D to get new products
to market. It pursues a diverse strategy to maintain and evolve its engagement in R&D.
• Otsuka and Pfizer set a consistent standard for stewardship and access plans, withcomprehensive plans for late-stage projects and strategies tailored to the product.
• Shionogi is first to publish the details of its antibacterial waste-management performance,
disclosing information on audit results for all antibacterial APIs and/or drug products
produced at relevant sites.
• Pfizer and Viatris use registration to expand availability of on-patent antibiotics, forceftazidime/avibactam (Zavicefta™) and pretomanid (Dovprela) respectively.
• Viatris uses a variety of strategies to improve the affordability and availability of its
anti-TB medicines among underserved populations.
• Ten companies are involved in technology transfers and other initiatives to enableantibacterial and antifungals medicines and vaccines to be produced locally.
• Shionogi remains the only company to fully decouple sales agents’ bonuses from sales
volumes of antibacterial medicines.
• Viatris, Otsuka and Johnson & Johnson have stopped their use of sales agents to promote
their anti-tuberculosis medicines in order to minimise the spread of resistance.
• GSK adapts Augmentin™ packaging to suit a range of patient needs and support
its responsible use.
• Pfizer remains only company to sharing raw data on AMR surveillance,
adding countries and pathogens.

9Antimicrobial Resistance Benchmark 2021

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Antimicrobial Resistance Benchmark 2021

2021
Antimicrobial Resistance
BenchmarkThe first section of this report provides an overview of how the pharmaceutical companies in scope performed, and whether – and where – progress can be identified.
AM R B E N CH MAR K PE R FO R MAN CE• Trends in pharma company action
Pharma shows bright points of progress against AMR, yet lags onaccess to antibiotics• How large research-based companies compare
Pfizer makes significant strides to become joint leader alongside GSK• How generic medicine manufacturers compare
Three new leaders in 2021, as stewardship and access measuresincrease
KE Y FI N D I N GS

• Appropriate Access
Pharma companies make limited use of the many ways to improveaccess to antibiotics• Responsible Manufacturing
Progress on limiting release of antibiotic waste into environment, but
gaps remain• Research & Development
Increased access and stewardship planning in R&D is hopeful sign forpoorer countries

11Antimicrobial Resistance Benchmark 2021

TRE N DS I N PHARMA CO M PANY ACTIO N

Pharma shows bright points of progressagainst AMR, yet lags on access to antibiotics
ANTI M I CRO B IAL RESISTANCE B E NCH MARK – 2021

Large research-based

Generic medicine

pharmaceutical companies

manufacturers

FI GU R E 1

100%

100%

Companies are evaluated only in thosenesses. Their scores are converted into60%

of points available per company. The

50%
47%

60%

67%

63%

69%

71%

bin
d
Ab o
bo
tt
Fre
Via
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tri
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ab
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a
A
Ha
ina lkem
nH
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ing

20%

maximum potential.

0%

Au
ro

GS
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Pfi
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&J
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No on
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Sa
no
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MS
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hn

company is to achieving 100% of its● Room to improve● Performance so far● Performance in 2020 ● Room to improveJo

0%

Benchmark compares how close each

15%

57%

50%

a percentage of the maximum number

46%

58%

63%

60%

68%

81%

84%

metrics that are relevant to their busi-

Good practice is becoming more common in the actionsclass of antifungals. It also includes GSK’s gepotidacin, now intaken by pharmaceutical companies to limit the threat ofPhase III and the only medicine candidate analysed** that is

antimicrobial resistance (AMR). This is most notable inbeing tested against N. gonorrhoeae. Almost a third of R&D

the plans to ensure wider access to and responsible use of

projects target drug-resistant M. tuberculosis, which causes

future products, as well as in the steps taken to curb thethe bulk of drug-resistant infections globally. A further third

release of antibiotic waste into the environment. In stew-

target Gram-negative bacteria, mainly Enterobacteriaceae.

ardship, generic medicine manufacturers are taking aThis includes Johnson & Johnson’s E. coli vaccine (ExPEC9V),

more active role. However, all companies miss opportuni-

which if successful could prove an important tool for prevent-ties to improve access in low- and middle-income countries

ing invasive extraintestinal pathogenic E. coli disease.

(LMICs), where the need is greatest and where people face
the greatest threat from superbug infections.

Plans to address the access to and stewardship of new
products in countries with high disease burdens have becomecommon, now covering 18 of the 20 medicine candidates in

While the antibacterial and antifungal R&D pipeline remains

Phase II or beyond. This is a significant improvement sincesmall compared to the scale of the AMR threat, there is a

the first Benchmark analysis, published in 2018, when only

slight increase in projects from the companies evaluated, anda handful of projects were covered by plans. Four compa-

there are more projects that target pathogens in the high-nies now report policies for access and/or stewardship plan-

est risk categories defined by WHO and the US Centers forning across their whole portfolios. Plans are expanding andDisease Control (CDC).* This includes Pfizer’s newly acquired

becoming more detailed, although quality assessments will be

antifungal candidate fosmanogepix, which targets pathogens

required as projects progress and new products are launched.

including C. auris and potentially represents the first in a new* Lists of pathogens identified as R&Dpriorities due to the threat from AMR
have been published by WHO and the
US Centers for Disease Control andPrevention (CDC). Both lists use multi-

ple categories to designate risk levels.
The highest levels are ‘critical’ (WHO) and‘urgent’ (CDC).

** R&D projects active between 22 June2019 and 30 April 2021, from the eightlarge research-based pharmaceutical companies in scope. By volume and value ofsales, these are the largest players in the

global antibiotics market that are active ininnovative R&D today.

12Antimicrobial Resistance Benchmark 2021

More R&D projects target pathogens in the

10 companies now require suppliers to limit the

One third of products assessed are covered byhighest risk categories defined by WHO andlevel of antibacterials present in manufacturing

access strategies

the CDC.

wastewaters
R&D projects

Companies

33

3

25
6

166
products

54

112
Fig. 4

Fig. 6

Almost all late-stage medicine candidates now

Companies report discharge levels are under

12 companies now take measures to mitigate

have both stewardship and access plans

set limits at 13.4% of sites

the risk of overselling antimicrobials

2020 2021

Late-stage medicine
candidates

Fig. 2● Generic medicine
manufacturers● Large R&D-based
companies

7

2020 2021

Companies

2
18

142

9

4
2020 2021

7

1,057
sites

Fig. 3915

4
3Fig. 5● No sales agents for atleast some medicines● Fully or partiallydecouples bonuses fromsales volumes

82020 2021

Fig. 7Companies are doing more to limit the impact of antibacte-

There are, however, a handful of encouraging examples ofrial manufacturing on drug resistance, including by enforc-

industry action that show the direction for improvement. For

ing good practice with upstream partners. Abbott, for exam-

example, almost all companies take steps to ensure an unin-ple, has introduced a new template contract for suppliers that

terrupted supply of antibiotics, such as implementing stand-specifically require them to meet AMR-related standards.

ardised forecasting processes, sharing demand data with

Pharmaceutical companies rely on a large cohort of third-

stakeholders on a regular basis and establishing global sup-party suppliers for their antibacterial ingredients. The base-ply networks. Further, ten companies are carrying out tech-line measure, as reported by the companies they supply, isnology transfers as a means of boosting supply, including inthat only 5.2% of third-party sites can be said to be compli-

five countries in Africa: Burkina Faso, Morocco, Nigeria, Southant with set limits. Nine companies in scope are actively mon-Africa and Zambia.

itoring levels at own sites, as well as requesting and reviewing
per-site discharge levels from third-party suppliers. Shionogi

Companies continue to improve stewardship efforts to safe-

sets the standard for transparency, by publishing detailed

guard the effectiveness of antimicrobial medicines, includ-

information on compliance with set limits at each site. No

ing how they tackle the risk of overselling. Once again, sev-

company has yet insisted that external waste-treatmenteral companies, including three generic medicine manufac-

plants also meet environmental standards relating to AMR.

turers, have newly developed or strengthened policies in thisarea. Aurobindo, Shionogi and Teva go furthest, either by not

Companies are improving the availability of products bypromoting their products or by fully decoupling bonuses fromregistering them for sale more widely in LMICs. Viatris,***sales volumes. One company, Cipla, has marginally weakened

for example, has filed its multi-drug-resistant tuberculosis

its policy on sales incentives, although it still goes further than

medicine pretomanid (Dovprela) in an additional 23 LMICs

other companies. Progress is clearer in other areas of stew-

since 2020. Nevertheless, the number of filings per coun-ardship, such as in monitoring the spread of resistance.

try remains low, and this low performance is mirrored in com-

Companies’ surveillance programmes cover a slightly

panies’ limited use of strategies to improve access to spe-broader range of pathogens on average than previously. Data-cific products. Only one third of the 166 products assessedsharing has also increased, although there is still only one

are covered by any access strategy in any of the 102 countries

company, Pfizer, that makes its raw data public. This is despite

assessed. Most products targeted by these strategies are

long-standing commitments from others to take the same

either vaccines, anti-tuberculosis medicines or some of thestep. Actions to mitigate conflicts of interest in educational

antibiotics that WHO deems a priority for greater access. As

programmes for healthcare professionals have become stand-in 2020, pharmaceutical companies are missing many oppor-

ard. This is a big change since 2018, when lines between mar-tunities to make antibiotics available in LMICs.

keting and educational activities appeared blurred.

***Formed in 2019 via a merger between
Mylan and Upjohn, a division of Pfizer.

13

Antimicrobial Resistance Benchmark 2021

HOW L ARG E RESE ARCH - BASE D CO M PAN I ES CO M PARE

Pfizer makes significant strides to become
joint leader alongside GSK
L ARG E RESE ARCH - BASE D PHARMACEUTICAL CO M PAN I ES – 2021 AM R B E NCH MARK
Overall performance - in %FI GU R E 8

Research Area performance - in points

100%

100

Left figure: compares how closeof its maximum potential.

81%

broken down by area of activity.

57%

50%

Points are available to companies in50

each metric that is relevant for its

Jo

so
n
hn

● Room to improve● Performance so far

Jo

0%

GS
K
Pfi
ze
&J
r
oh
ns
o
n
No
va
rti
s
Sa
n
Sh ofi
ion
og
i
Ot
su
ka
MS
D

business.

hn

so
n

&J

GS
K
Pfi
ze
r
oh
ns
o
n
No
va
rti
s
Sa
no
fi
Sh
ion
og
i
Ot
su
ka
MS
D

46%

58%

points each company achieved,
60%

68%

Right figure: shows how many
63%

84%

each company is to achieving 100%

0
● R&D
● Responsible Manufacturing● Appropriate Access● Stewardship● Points still available

GSK and Pfizer are joint leaders of the large research-is one of only four companies to report that 100% of its man-based companies in 2021. They are followed by Johnson &ufacturing sites are in compliance with the discharge limits

Johnson. Although all three leaders perform well across thethat it has set. Further, GSK reports that 93% of its suppliers’

board, Pfizer made significant improvements in the scale

sites are compliant with discharge limits. It performs less welland scope of its efforts to address AMR, and signalled ain stewardship than the other leaders, as it only partly decou-

clear boost to its infectious diseases R&D.

ples performance incentives for its sales agents from the volumes of sales they can secure.

GSK is the clear leader in Research & Development, with 31
R&D projects. About half of its pipeline comprises vaccines

Pfizer has expanded its R&D pipeline to 13 projects, up fromprojects, the largest number of any company in scope. One

eight in 2020, including those from its acquisitions of the bio-

third of its projects (11) target pathogens classed as posing atechnology companies Arixa Pharmaceuticals and Amplyx

critical and/or urgent threat from AMR, more than any otherPharmaceuticals. These moves added innovative antibacte-company. GSK reports access and/or stewardship planningrial and antifungal projects to its pipeline. Of the companies

for all of its late-stage projects, and the detail of its reported

evaluated, Pfizer has the most late-stage projects that areplans has increased following the implementation of its pro-already covered by plans for ensuring access, including reg-

cess for developing such plans in Phase III for all projects. GSK

istration commitments and equitable pricing strategies, as

14

Antimicrobial Resistance Benchmark 2021

GSK performance by research area

Pfizer performance by research area

Johnson & Johnson performance by research
area

Points

93%

R&D

87%

Manufacturing

80%

Access75%

Stewardship
0%50%

Points28/ 30

R&D

Points77%

23/ 30R&D

50%

13/ 15

Manufacturing

80%

12/ 15

Manufacturing

20/ 25

Access80%

28/ 35

Access15/ 20

Stewardship18/ 20

Stewardship

100%

90%
0%

Fig. 950%

100%

15/ 3080%

12/ 1572%

18/ 25

80%
0%

50%

16/ 20100%

Fig. 10

Fig. 11well as measures to strengthen supply and ensure steward-

Although not in the leadership group, Sanofi, Shionogi andship. Pfizer stands out for filing its on-patent antibacterial andOtsuka each show good practice in specific areas. Sanofi, for

antifungal medicines across a total of 33 of the 102 low- andexample, is taking steps to ensure a continuous supply of its

middle-income countries in scope for access metrics. This

products, including by carrying out technology transfer initi-

includes a move to file one medicine (ceftazidime/avibactam)

atives in countries such as India, Nigeria, and Vietnam, within 18 further countries since 2020. Pfizer leads in Stewardshipthe transfer in Nigeria having been supported since 2008.

overall, and is the only company that publicly shares raw data

Compared to the other companies evaluated, Shionogi con-from its AMR surveillance programme. It misses out on thetinues to invest the highest proportion of its revenues in anti-

top spot as it picks up a smaller proportion of the points avail-bacterial and antifungal R&D, and is one of only two compa-

able to it than GSK. Nevertheless, Pfizer has demonstrated

nies to publish detailed information on which sites, includ-strong progress in each Research Area.

ing those operated by third-party suppliers, meet set limits on
the concentration of antibacterials in wastewaters. Otsuka, as

Johnson & Johnson follows Pfizer. It performs well

well as Johnson & Johnson, does not deploy sales agents forin all three Research Areas, particularly in Responsible

its anti-tuberculosis medicine.

Manufacturing. It reports a comprehensive environmental
risk-management strategy for limiting the impact of its manu-

MSD* has gained the most approvals of new antibacterials

facturing practices on drug resistance. The company extends

since 2020, but performs less well than its peers as it remains

the limits it sets at its own sites to its third-party suppliers,

unwilling to share data beyond what is already in the public

proactively reviewing the discharge levels they report. It has

domain. MSD has published a general commitment to expand-a mid-sized R&D pipeline of 14 projects; three more than ining access to its products, but provides little insight into

2020. This includes two antibacterial vaccines, including thewhere specifically it has filed its products for registration, or

only vaccine candidate identified that targets E. coli. Both

into its strategies to expand access.

WHO and the CDC place resistant E. coli in their highest risk
categories. Johnson & Johnson employs a range of access

These eight companies represent the bulk of the large

strategies to expand access to its on-patent medicine, bedaq-

research-based pharmaceutical companies currently active inuiline, in all 30 countries that face a high-burden of multi-drug

infectious diseases R&D. Most of the R&D into antibacterial

resistant TB identified by WHO. Yet it provides limited infor-

and antifungal pathogens depends on smaller biotech compa-

mation on access strategies for off-patent/generic medicines.

nies. Nevertheless, the companies evaluated here are conducting R&D that targets pathogens in the highest AMR threat cat-

Novartis performs strongly in Responsible Manufacturing

egory. The effectiveness of any successful new product must

and Appropriate Access, yet has fully retreated from anti-

be preserved for as long as possible, which depends on com-microbial R&D with no projects that target priority patho-prehensive access and stewardship plans, but also on growing

gens in its clinical pipeline. As a result, it sits in fourth place.

the pipeline of replacement medicines. As some of the largest

It is progressing in access to its off-patent/generic medi-

producers of antibacterial and antifungal medicines and vac-cines, for example by registering its amoxicillin/clavulanic acidcines, these companies have significant capacity to improve

antibacterial in 70 of the countries in scope for the access

access to their products in the countries with highest need andmetrics. Novartis also runs two broad initiatives that aim torisk of resistance. Access in low- and middle-income countries

expand access to its off-patent/generic medicines, namely thecan be provided via a range of actions from registering med-Novartis Access programme and the Novartis Sub-Saharanicines and vaccines to building up the skills, knowledge andAfrican (SSA) Unit. In a change since 2020, it now also sup-expertise needed for local manufacturing, and strengthening

ports an AMR surveillance programme, running in Poland,

supply chains to prevent shortages, while taking each popula-which publishes its aggregated results.

tions’ ability to pay into account in pricing policies.

*Merck & Co., Inc (Kenilworth, NJ, UnitedStates).

15

Antimicrobial Resistance Benchmark 2021

H OW G E N E RI C M E D ICI N E MAN U FACTU RE RS CO M PARE

Three new leaders in 2021, as stewardship andaccess measures increase
G E N E RIC M E D I CI N E MAN U FACTU RE RS – 2021 AM R B E NCH MARK
Overall performance - in %FI GU R E 12

Research Area performance - in points

100%

Left figure: compares how closeeach company is to achieving 100%

55

50%
47%

60%

points each company achieved,
60%

63%

69%

Right figure: shows how many
67%

71%

of its maximum potential.

broken down by area of activity.
Points are available to companies ineach metric that is relevant for its

0

Au
ro

bin
d
Ab o
bo
tt
Fre
Via
se
tri
niu
s
sK
ab
i
Cip
la
T
Su
n P eva
ha
rm
a
A
Ha
ina lkem
nH
ail
ing

15%

0%

Au
ro

bin
d
Ab o
bo
tt
Fre
Via
se
tri
niu
s
sK
ab
i
Cip
la
T
Su
n P eva
ha
rm
a
A
Ha
ina lkem
nH
ail
ing

20%

business.

● Room to improve● Performance so far● Responsible Manufacturing● Appropriate Access● Stewardship● Points still available

Aurobindo, Abbott and Viatris take the lead among theand antifungal medicines and ensures that its one educational

generic medicine manufacturers in 2021. Each of these com-

programme for healthcare professionals mitigates the risk

panies is filing its medicines for registration in low- and mid-of conflict of interest. As part of its environmental risk-man-

dle-income countries, and has improved its sales practices

agement strategy, Aurobindo not only sets limits but tracks

to mitigate the risk of overselling. Abbott, Cipla and Viatrisand reports compliance with discharge limits at its own sites.

are the first generic medicine manufacturers to report envi-

It also requires its two reported third-party suppliers to fol-ronmental risk-management strategies that apply to their

low the same limits. Moreover, Aurobindo now discloses more

suppliers’ sites, as well as their own sites. They also reportstrategies to ensure a continuous supply of its medicines,that they check whether suppliers’ sites comply with limits

including steps to prevent shortages.

set for environmental standards. Transparency by generic
medicine manufacturers has once again increased, amidst

Abbott has also progressed significantly in its stewardship

the COVID-19 pandemic.

and manufacturing measures since 2020, including sharing
more data. This includes adapting packages to make it easier

Aurobindo is the overall leader, having progressed signifi-

for patients to follow good stewardship practices. It is also tri-

cantly in its stewardship measures since 2020. It reports thatalling changes to its sales practices in order to limit oversell-

it does not deploy sales agents to promote its antibacterial

ing. In India, it ran a three-month pilot whereby performance16

Antimicrobial Resistance Benchmark 2021

Aurobindo performance by research area

Abbott performance by research area
PointsPointsR&D

0%

Manufacturing

67%
60%

Access87%

Stewardship
0%

50%

0%

0/ 0

R&D

10/ 15

Manufacturing

9/ 15

Access13/ 15

Stewardship

100%

Viatris performance by research area

73%
53%
80%

0%

50%

Fig. 13

Points

0%

0/ 0

R&D

11/ 15

Manufacturing73%

11/ 15

8/ 15

Access72%

18/ 25

12/ 15

Stewardship

100%

0/ 0

53%
0%

50%

8/ 15
100%

Fig. 14

Fig. 15

incentives for its sales agents were decoupled from the sales

all sites by March 2022. Cipla is currently conducting an initial

volumes they could secure for a specific anti-infective prod-assessment of all suppliers with the intent of extending AMR-

uct. Abbott performs well in responsible manufacturing, as

related environmental standards to these sites, also by March

it now measures the levels of antibacterial residue remain-2022.

ing in wastewater at its own sites to assess compliance with

Hainan Hailing and Alkem trail in this group, as they remain

specific limits and extends these standards to some supplier

the only two generic medicine manufacturers to demonstratesites. In 2021, it introduced a new contract template for sup-limited transparency. They do not share data that enable thepliers of APIs and drug products with clauses that requireevaluation of their commitment to limiting AMR.

suppliers to implement specific AMR-related environmental
standards.

That the generic medicine manufacturers are expanding
their efforts against AMR is clear. For the first time, several

Viatris was formed in 2020 through the combination ofsuch companies are requiring their suppliers to meet spe-

Mylan and Upjohn, a division of Pfizer. It performs well withcific limits on the levels of antibacterials present in wastewa-

regards to its manufacturing practices as well as its strategies

ters. Their progress in stewardship is noted in the increased

to ensure a continuous supply of products, for example, toscores, specifically around sales practices, efforts to mitigate

address the risk of shortages. It reports that all its own sites

the risk of conflict of interest in educational programmes,

are compliant with discharge limits and reports that its ZLD*

and in how they adapt product packaging to facilitate stew-sites that manufacture antibiotics test recycled waters forardship. More of these companies are reporting strategies forthe presence of antibacterials, which were found to be zero. It

improving access to their products in low- and middle-income

extends its standards and limits to its third-party supplier, andcountries, including to ensure a continuous supply. This is arequests and reviews discharge levels as part of audit require-

positive sign, as much more needs to be done.

ments. Further, it employs conflict of interest mitigation for
its AMR-related education programmes for healthcare profes-

Pharmaceutical companies have a responsibility to ensuresionals and is active in two AMR surveillance programmes.

that their medicines are accessible and are reaching those in
need. The poorest countries are home to nearly 700 million

Cipla dropped from leader in 2020 to fifth in 2021 as otherpeople and are particularly overlooked by companies’ accesscompanies push forward with improved practices in each ofstrategies. Only four generic companies out of nine report

the research areas. It misses opportunities to improve thethat they use access strategies in low-income countries foravailability and accessibility in low- and middle-income countries of its on-patent medicine, plazomicin (Zemdri®), which

specific products, and more must be done to improve accessit acquired in 2019. Plazomicin has now been registered in

medicine manufacturers have a responsibility to ensure an

India. However, Cipla does monitor and report the numbers of

uninterrupted supply of good quality products. These compa-

people it reached with off-patent/generic medicines in India

nies have an opportunity to improve supply security by imple-

and South Africa during the COVID19 pandemic. In 2020,

menting strategies such as demand planning and data shar-

Cipla had fully removed the link between sales volume anding, and by mitigating against the risk of shortages via suf-

bonuses offered to its sales agents. In 2021, a small portion officient buffer stocks. They can also contribute to scaling up

its bonuses (1%) have been reconnected with sales volume.

local capacity by supporting local manufacturing hubs andNevertheless, Cipla performs well in Stewardship, and is tak-entering technology transfers with originators.

to medicines as well as to expand access to vaccines. Genericing action to limit the impact of its manufacturing operations
on resistance. While no longer a member of the AMR Industry
Alliance, it sets discharge limits and quantifies the actual levels of antibacterials present in wastewaters at some sites. It
has committed to ensuring that it is measuring these levels at*Zero Liquid Discharge is a waste-treatment process in which no wastewater isdisposed into the environment.

17

Antimicrobial Resistance Benchmark 2021

KE Y FI N D I NG 1: APPRO PRIATE ACCESS

Pharma companies make limited use of themany ways to improve access to antibiotics
Vital antibiotics and antifungals are not reaching the populations ofpoorer countries. Key examples show what pharma companies can
do to improve this bleak picture.
▶ Just one third of products are covered by any access strategy in any of the lowand middle-income countries in scope▶ A handful of encouraging examples of pharmaceutical company action
suggest possibilities for change
Pharmaceutical companies are not taking the necessary steps

Product registration in local markets is a vital first stepto provide access to the antibiotics and antifungals in theirin making medicines widely available. There has been incre-

portfolios in low- and middle-income countries (LMICs) – andmental progress here, but products are still not widely filed inwhere access strategies are in place, they remain focused on

LMICs. The 2021 Benchmark found only six on-patent med-a small set of countries, people, and diseases. However, there

icines had been filed in 10 or more of the 102 countries inare clear and tangible ways that access could be improved,

scope, including 30 filings for Johnson & Johnson’s MDR-TB*

and strategies which could make a real difference to millions

medicine bedaquiline, and 25 for MSD’s ceftolozane/tazo-of people if deployed more widely.

bactam, which is used to treat complicated urinary tract andintra-abdominal infections. These numbers are an improve-

Why does this matter?

ment from just four products with more than 10 filings in the

The world’s poorest countries experience the greatest rates

2020 Benchmark, but the figures are still too low.

of infectious disease and the highest levels of antibiotic

Registration, however, is only part of the story. There areresistance – but it is precisely these countries that suffer thea wide range of tools available to pharmaceutical companies

biggest gaps in access to appropriate medication.

to increase local availability of vital antimicrobials in poorer

An estimated 5.7 million people, mainly those living in

nations, such as tiered pricing, voluntary licensing agree-

LMICs, currently die each year from lack of access to anti-

ments, technology transfers, and public-private partnerships.

biotics. Unavailability of suitable antibiotics has a huge toll

Under certain circumstances, patient assistance programmeson those directly affected, but is also a hazard for the world,and donations can also be used to increase access.

because doctors often resort to suboptimal treatments when

Several companies are showing what can be done in thisthe right medicines are unavailable. This gives pathogens anspace. For example, GSK provides access to its antibacterial

opportunity to develop resistance.

vaccines through tiered pricing policies and public or private
partnerships, including with Médecins Sans Frontières andWhat did the Benchmark analysis find?

UNICEF.

The 2021 Antimicrobial Resistance Benchmark examined theaccess strategies used by pharma companies for a total of 166

FIGURE 16. What is the data set?

established antibacterial and antifungal medicines and vac-

Across the 17 companies in scope (eight large research-based companies

cines. Of these, only 54 – just one third – are reported to be

and nine generic medicine manufacturers), 166 products have been selected

covered by at least one access strategy in any of the 102 LMICs

for analysis. The Benchmark examines the pharma companies’ accessin scope. The remaining 112 products are either not covered bystrategies in relation to 102 low- and middle-income countries, where

any access strategy, or the data has not been made available byimproved access to medicine is most urgently needed.

the companies.
Breaking down those 166 products (see fig, right), only 26%
of off-patent/generic medicines are covered by access strategies, compared to 46% of the on-patent medicines. The picture
is better for on-patent vaccines, with 72% supported by at least
one access strategy – likely reflecting the role of supranational
procurement mechanisms such as Gavi, The Vaccine Alliance.

On-patent
vaccines

18 17

On-patent
medicines

166
products

131
Off-patent/generic
medicines* Multidrug-resistant tuberculosis

18Antimicrobial Resistance Benchmark 2021

While the use of technology transfers is limited – with ini-

Otsuka’s delamanid (Deltyba®) were distributed across moretiatives being undertaken in only 14 of the countries in scopethan 80 countries. Viatris is now a generic licensee of delama-– this approach could be a cornerstone for long-term security

nid, which will help increase access to this medicine.

of supply and access.
Pfizer is one of the 10 companies with at least one such ini-

What needs to happen next?

tiative in place, working with the South African government

The industry needs to reach more people with more prod-

and Biovac Consortium Cape Town to produce its pneumococcal vaccine Prevnar13® locally, from raw materials to fullyucts, both old and new. Current industry access strategies doreleased and packaged products.

patients are still not receiving the life-saving medicines they

In terms of medicines, Novartis partners with third par-not go far enough, and many of the world’s most vulnerable
need. Future strategies need to increase in quality and reach,ties to produce penicillin products in Pakistan and to transfer

in order to cover a wider range of countries, people, andmanufacturing knowledge – which is significant for patientstreatments – with the fragments of different strategies com-as penicillin is such a widely-needed antibiotic. Meanwhile,

ing together to form a more comprehensive picture.

Sanofi has been involved in technology transfers in Nigeria

With each medicine or vaccine, pharmaceutical compa-

since 2008, enabling a local site to manufacture products
including metronidazole (Flagyl®), an antibiotic used to treat anies should consider the full range of access strategies in therange of conditions from bacterial vaginosis to skin infections.

ing affordability into account. This encompasses registering

toolkit to work out what is most useful, while always tak-Access strategies have also been widely used to get tuber-products more widely, including in the poorest countries; fur-culosis medicines to the places where they are most needed.

ther donations and patient assistance programmes; voluntary

For example, in 2020, more than 125,000 treatment coursesof Johnson & Johnson’s bedaquiline (Sirturo®) were orderedlicensing; entering into partnerships with external stakehold-through Stop TB Partnership’s Global Drug Facility, andand reduce the risk of shortages; and investing in local capaci-

between 2016 and 2020 at least 25,000 treatment courses ofty-building and technology transfers.

FIGURE 17. Number of products covered by at least one accessstrategy, broken down by category
Of the 166 products examined by the Benchmark, 54 are covered by at least
one access strategy. A wide range of strategies count towards this figure,ers to increase access; schemes to ensure continuous supply

On-patent medicines

7

On-patent vaccines

13 5

10

Off-patent/generic medicines

including donations, patient assistance programmes, voluntary licensing, andtiered pricing policies.

34
0

Covered by at least one
access strategy

97
50

100

150

Not covered byaccess strategy, or
coverage is unknown

FIGURE 18. 10 pharma companies support local manufacturing projects across 14 low- andmiddle-income countries
Of the 17 companies covered by the Benchmark, 10 report that they are supporting local manufacturing(such as by carrying out technology transfers) in at least one of the 102 low- and middle-income
countries in scope. This map shows the countries where at least one project is taking place.

● Countries where companies aresupporting local manufacturing

19

Antimicrobial Resistance Benchmark 2021

KE Y FI N D I NG 2: RESPO NSI B LE MAN U FACTU RI NG

Progress on limiting release of antibiotic waste
into environment, but gaps remain
Pharma companies are taking steps to curb the release of antibiotic
waste into the environment. They must now go further byconsistently setting and enforcing limits at suppliers’ sites.
▶ More companies are setting and enforcing limits at their own sites, and are now
starting to expand these standards to supplier sites▶ However, just 5.2% of third-party manufacturing sites are reported
as compliant with limits on antibacterial waste disposal▶ Shionogi and GSK are leading the way in tracking and requiring
compliance from suppliers
Pharmaceutical companies are increasingly taking action to

While there has historically been little transparency into

limit the release of active pharmaceutical ingredients (APIs)

how and whether companies work with their suppliers to

into the environment, by setting and enforcing discharge lim-

limit the release of antibacterial waste into the environ-its on wastewater from manufacturing sites. While a huge gap

ment at suppliers’ sites, clear progress can be identified. The

remains in ensuring that the same standards apply at man-2018 Benchmark found that only three out of 13 companies

ufacturing sites operated by pharma companies’ third-party

required suppliers to set discharge limits,** and this has stead-suppliers, progress by a few companies demonstrates that

ily risen, with 10 companies out of 17 now reporting that theyclosing this gap is entirely possible.

set discharge limits.

Why does this matter?

ing and reporting on compliance with these limits. According

If waste from the manufacture of antibiotics contains a highto the data made available, while limits are set at the majority

concentration of APIs when it is discharged into the environ-of suppliers’ sites used by those 12 companies (64%), just one

ment, there is a serious risk it will contribute towards antimi-

fifth of sites measure discharge levels to check for compli-

crobial resistance (AMR). While solid waste is typically sent

ance. Only 45 of the 870 suppliers’ sites (5.2%) were reported

for incineration or to landfill, liquid waste is discharged into

to the Benchmark as compliant.

However, setting limits only works if companies are track-environments such as rivers, where APIs can cause bacteria togain new and dangerous forms of resistance.

It is good news that some pharma companies are now
working with their suppliers to improve standards, and thatIn the short term, the release of APIs into the environment
poses the most risk to the health of people living near the

FIGURE 19. Uptick in companies requiring all suppliers to set discharge

manufacturing sites. But in the longer term, resistance inevi-

limitstably spreads and contributes to the global problem.

Since the first Benchmark was published in 2018,** there has been an
encouraging increase in the number of companies requiring suppliers to set

What did the Benchmark analysis find?

limits on antibiotic wastewater discharge into the environment.

The 2021 Antimicrobial Resistance Benchmark asked 17 large
research-based companies and generic medicine manufacturers to disclose the number of sites they and their suppliers

11

use to manufacture antibacterial APIs and drug products, aswell as their environmental practices regarding AMR. Fifteencompanies provided data about their own sites, and 12 also

103provided information about their suppliers’ sites.*
The picture is most positive at the 187 directly-operated
sites under analysis, with large research-based companies
reporting compliance at over two thirds of their own manufacturing sites, and generic medicine manufacturers reporting

7

6

7

3
2018 2020 2021

Generic medicine
manufacturers which require
suppliers to set limits
Large research-based
pharma companies which
require suppliers to set
limitscompliance at just over one third of their own sites.
* No data on any manufacturing sites isavailable for Alkem and MSD. No data on
suppliers’ sites is avaiable for Fresenius
Kabi, Hainan Hailing and Sun Pharma.

** In 2018, the following four companies
were not in scope: Abbott, Alkem, Hainan
Hailing and Otsuka. They have been in
scope of the Benchmark since the 2020
report. The other 13 companies whichhave remained constant since the 2018
Benchmark are GSK, Pfizer, Johnson &Johnson, Shionogi, Novartis, MSD, Sanofi,
Sun Pharma, Cipla, Teva, Fresenius Kabi,
Aurobindo, and Viatris (formerly Mylan).

20

Antimicrobial Resistance Benchmark 2021

now provides the opportunity to push the remaining 95% ofWhat needs to happen next?

the sites to not only set limits, but to actively monitor and

There has been clear movement in the right direction over thereport on compliance.

last few years as pharma companies increasingly report set-

GSK, for example, reports that antibacterial waste dis-ting and adhering to limits at their own sites.

charges at 37 out 39 of its suppliers’ sites are now compliant

Pharma companies must now ensure that limits are set on

with set limits. Shionogi has recently made public which of its

antibacterial wastewater discharge at all of their suppliers’

own sites and suppliers’ sites are compliant with limits, andsites. This is especially important given just how many third-

Abbott reports having set enforceable contractual provisions

party manufacturing sites are involved in the supply chain

related to environmental standards.

(comprising 82% of the total sites covered by this analysis).

Other leaders on environmental risk-management strat-

Pharma companies should continue to set limits, as well as

egies include Novartis, Johnson & Johnson, and Pfizer, all of

making sure compliance with these limits is assessed at each

which report that they quantify discharge levels against set

site. This must be established via supply contracts and qual-

limits at their own sites, and that they ask their suppliers to

ity agreements, and companies should enforce those agree-

set limits and report discharge levels.

ments when limits are exceeded.

The drive to cut waste discharge levels is complicated by

In this way, change will be carried all the way throughthe fact that there is currently no internationally-agreed reg-

the supply chain from start to finish, and fewer antibacteri-ulation on standards on safe concentrations of antibacteri-als will be discharged into the environment – which would be

als released into the environment. Instead, companies com-significant progress in the fight against rising antimicrobial

mit to voluntary targets recommended by the AMR Industry

resistance.

Alliance, which means there is a reliance on self-regulationand self-reporting.
FIGURE 20. Number of manufacturing sites reported as compliant with antibacterial
discharge limits
The first figure shows how many of the 1,057 sites are directly operated by large research-based
companies and generic medicines manufacturers, and how many are operated by third-party suppliers.
It also shows how the 142 sites reported as compliant are distributed between these three categories.
The second figure breaks these raw numbers down into percentages.

Sites operated by:Sites operated by:Large research-based companies

63 30

Large research-based companies

Generic medicine manufacturers

34 60

Generic medicine manufacturers

Third-party suppliers

45
0
200

400

600

825
800

Reported as compliant with limits

67.7%
36.2%

Third-party suppliers
1000
Sites

63.8%

5.2%
0%

50%

Reported as compliant with limits

Reported as not compliant, or no data available

32.3%
94.8%
100%
Sites

Reported as not compliant, or no data available

FIGURE 21. Companies require suppliers to set limits, but many do not assess whether limits are
actually achieved
This figure shows how many sites, out of the total of 870 suppliers’ sites, are reported as being required
to set limits; how many are reported to quantify discharge limits; and how many are reported ascompliant with those limits.
Reported sites thatare required to set
limitsReported as compliant with limits- Reported as not compliant, or no data
available

Reported sites thatquantify

Sites reported as compliant
with limits

45

173
309

870
sites
561

561
sites withlimits173
sites thatquantify

388
Reported sites
without limits,
or no data available

Reported sites that
do not quantify,
or no data available

124

Sites where results
are not reported
4
Sites reported as
not compliant

While 561 supplier sites are required
to set discharge limits, only 173of those quantify discharge levels
to determine whether limits are
exceeded.
That leaves 388 sites where,
although limits are being required,
no actions are reported as being
taken to check whether the actuallevels of antibacterial residue in
wastewaters are compliant withthese levels. This shows that companies need to ensure that discharge levels are actually quantified
at all supplier sites.

21

Antimicrobial Resistance Benchmark 2021

KE Y FI N D I NG 3: RESE ARCH & D EVE LO PM E NT

Increased access and stewardship planning in
R&D is hopeful sign for poorer countries
Pharmaceutical companies are making more – and, potentially,
better – access and stewardship plans for their future medicinesand vaccines.
▶ Small R&D pipeline for antibiotics and antifungals means access and stewardshipplanning is essential for each new product▶ 18 out of 20 late-stage medicine projects in this analysis have both access &stewardship plans in place, a marked increase since previous Benchmarks
Large research-based pharma companies are increasingly

example, has added depth and specificity to its plans, which

treating access and stewardship planning as an integral part

include a wide range of strategies to ensure access in low-of the R&D process, making and sharing plans for a growing

and middle-income countries (LMICs), such as filing for reg-

proportion of their late-stage clinical projects. There are also

istration, equitable pricing, and measures to strengthen sup-signs that these plans are becoming more in-depth and more

ply. Both Pfizer and Otsuka report detailed and varied accesstailored, which means that new treatments will be more likely

and stewardship plans for most late-stage medicine projects

to reach people who need them – wherever they live.

in the pipeline. Progress is also seen in the case of Shionogi,
which has now signed a Memorandum of Understanding with

Why is this important?

the Global Antibiotic Research and Development Partnership

Given the frequent unavailability of medications in many

(GARDP) and the Clinton Health Access Initiative (CHAI) to

poorer countries, as well as the rising threat of drug resist-

accelerate access to its late-stage antibiotic cefiderocol for

ance, there is an acute need for pharma companies togram-negative bacterial infections in patients with limited

improve their access and stewardship planning. It is especiallytreatment options.

important that these plans are baked into the R&D process
for new antibiotics and antifungals, for two major reasons.

The range of stewardship and access plans which the companies intend to enact when their late-stage projects areFirstly, despite some improvements in recent years, there

launched includes registration commitments, potential tech-

are still not enough products in the pipeline to replace thosenology transfers to generics companies, tender agreements

losing their effectiveness – so it is essential that pharma com-

to bring down prices, and surveillance programmes.

panies ensure each new medicine is protected from misuse and overuse; and secondly, access to new medicines and

FIGURE 22. More stewardship & access plans for late-stage projects

vaccines can be life-changing for those suffering the great-

Among the eight large research-based pharma companies in scope, theest burden of resistant infections. Plans must therefore

Benchmark identifies antibacterial and antifungal projects in late-stage clinicalalready be established while any new product is still in clinicaldevelopment (Phase II and onwards) that target priority pathogens.**

development.

This figure looks at how many of those medicine projects have access and/or
stewardship plans in place, and how many vaccine projects have access plans

What did the Benchmark analysis find?

in place (with stewardship not being a concern for vaccines).

The Antimicrobial Resistance Benchmark has closely examined this area since the first report in 2018, when only two

Medicines R&D projectsof 28 antibiotics in late-stage clinical development had both2020

access and stewardship plans in place. Zooming in on the2021eight large research-based companies in the Benchmark’s

40

scope, there has since been an upward trend, with four out of
13* late-stage medicine R&D projects covered by both access2020

of 20 late-stage medicine R&D projects in this latest report.

2021

in this area include Pfizer, Otsuka and Shionogi. Pfizer, for* The 2020 Benchmark also included
small- and medium-sized enterprises(SMEs) in its scope, so the total figurefor all companies was eight out of 32
projects.

** Bacteria and fungi identified as priority R&D targets for limiting AMR by the
WHO and/or the US Centers for Disease
Control and Prevention (CDC). See
Appendix V.

5

3

10

15

Access and stewardship plans

Access plans

18 1 120
Neither

Vaccines R&D projects

and stewardship plans in the 2020 Benchmark; this rises to 18
Companies that have significantly improved their efforts

6

8
0

5
Access plans

4
11
10

15

20

No access plans

22Antimicrobial Resistance Benchmark 2021

GSK, which has five late-stage R&D projects included in

What needs to happen next?

this analysis, employs an equitable pricing strategy framework

Pharma companies must make sure that they put access andin LMICs and as part of its Launch Excellence programme.

stewardship plans in place for every single one of their medi-

From Phase III onwards, GSK develops launch plans for eachcines in late-stage clinical development, and that they likewisemarket based on disease burden, regulatory requirements,

support their vaccine projects with access plans.

market readiness and market archetype.
Companies behind five of the 11 vaccines in late-stage tri-

In addition, plans for each new product must become morecomprehensive, with companies considering using multiple

als have plans to apply for WHO prequalification and to part-

strategies – and deploying them more widely, with tailoring toner with Gavi, The Vaccine Alliance, to make their vaccines

local needs. Promising steps in the right direction would thenavailable to the populations that need them most. For example, Sanofi has developed its paediatric vaccine Shan6™ spe-

accelerate into strides.

cifically for the LMIC market, with an extensive access planucts reaching the final stages of the R&D pipeline. In a Junethat includes local manufacturing, equitable pricing strate-

2021 research paper, the Access to Medicine Foundation

gies, WHO prequalification, and sustainable manufacturingfound that small- and medium-sized enterprises (SMEs)

and supply.

account for 75% of all clinical-stage antibiotics in develop-

Overall, the Benchmark identifies particularly strong access

It would also be helpful to see a greater number of prod-

ment.and are pivotal in driving new antimicrobial innovationand stewardship plans when it comes to tuberculosis prod-– yet these smaller biotechs often face funding shortfalls anducts, supported by consistent proritisation by funders andbankruptcy, leaving promising new drugs stranded on theinternational organisations. Johnson & Johnson’s MDR-TB*

lab bench. As outlined in the report, there is much that large

medicine bedaquiline has been made widely available throughpharmaceutical companies can do to address this problem.**the Stop TB Partnership’s Global Drug Facility, and Otsuka is

If and when their late-stage medicines and vaccines reach

now taking a similar approach by partnering with the Bill &the market, pharmaceutical companies must follow throughMelinda Gates Foundation as it makes plans for its own late-

and turn their commitments into a reality. That means regis-

stage TB candidate.

tering new products in large numbers of LMICs, and executing
the access and stewardship plans to the fullest extent.

TABLE 1. Access and stewardship plans cover a diverse range of strategies
The table shows the range of strategies that the eight companies are incorporating in their stewardshipand plans. The most appropriate strategies depend on the product in question – not all strategies areapprioriate for all products. Companies that have improved their efforts in access and stewardshipplanning for antibacterial and antifungal medicines include Otsuka, Pfizer and Shionogi.

SanofiShionogi

PfizerMSD

OtsukaJohnson & Johnson

GSK

Access strategies

Registration

●

●

●

●

●

●

○

WHO Prequalification Programme

○

○

○

●

●

●

○

WHO Collaborative Procedure for Accelerated Registration

○

○

○

○

○

○

○

EMA Article 58

○

○

○

○

○

○

○

Responsible IP and licensing arrangements

●

○

○

●

●

○

○

Managed access programmes

○

●

○

●

●

○

●

Product donation programmes

○

●

○

○

○

○

○

Special importation waivers

○

○

○

○

○

○

○

Sustainable manufacturing and supply

○

○

○

●

●

●

○

Equitable pricing

●

●

○

●

●

●

○

●

●

●

●

●

○

●

Stewardship strategies Surveillance
Responsible promotion

○

○

○

○

○

○

○

Availability of companion diagnostics

○

○

○

●

○

○

○

* Multidrug-resistant tuberculosis** Biotechs are saving the world fromsuperbugs. Can they also save themselves?, Access to Medicine Foundation,
June 2021

23

Antimicrobial Resistance Benchmark 2021

24

Antimicrobial Resistance Benchmark 2021

Research Areas

The 2021 Antimicrobial Resistance Benchmark looks at companies’ performance in terms of R&D, Responsible Manufacturing, and Appropriate
Access and Stewardship. The Benchmark’s findings are covered in fourchapters, each of which lays out the data collected about the companies
in scope – and analyses this information to draw out conclusions.

FOU R RESE ARCH CHAPTE RS
Research & Development

Responsible Manufacturing

Appropriate Access

Stewardship25

Antimicrobial Resistance Benchmark 2021

26

Antimicrobial Resistance Benchmark 2021

CO NTEX T

Research & Development
As drug resistance rates rise, medicines become less effective, increasing the need for new ones that can replace them.
Yet few new antimicrobial medicines have reached the market
in recent decades, and the collective pipeline remains small. The
World Health Organisation (WHO) and US Centers for Disease
Control and Prevention (CDC) have identified drug-resistant bacteria and fungi that pose the greatest threat to human health.
These include the superbug C. difficile, and carbapenem-resistant Enterobacteriaceae, and comprise the priority targets forresearchers working in antibacterial and antifungal R&D. The 2021
AMR Benchmark examines the R&D projects that target thesepathogens in the pipelines of eight large research-based pharmaceutical companies. The aim is to capture how these companies
are supporting global efforts to replenish and protect the antimicrobial pipeline.

KE Y CO NTEX T
Antimicrobials are at the heart of modern medicine
Antibacterial and antifungal medicines and vaccines are crucial to effective infection prevention and control programmes. Furthermore, antimicrobial medicines also
make other procedures and treatments safer, such as surgery, cancer therapy andimmunesuppresant treatments.
New medicines and vaccines are urgently needed
Bacteria and fungi can develop drug resistance through the selective pressure
imposed by antimicrobials or by sharing genetic material. New medicines areneeded to replace those that are losing effectiveness. New vaccines curb resistanceby preventing infection in the first place.
Which pathogens are most dangerous?
WHO and the CDC have each published lists of bacterial and fungal pathogens thatthey view as posing the greatest risk to human health due to resistance.
What is the role for large research-based pharmaceutical companies?
Large research-based pharmaceutical companies have the resources, capacities,
and expertise to ramp up antibacterial and antifungal R&D considerably, and to support development by smaller R&D-focused enterprises .

27

Antimicrobial Resistance Benchmark 2021

Research & Development – context

Which companies does the 2021 Benchmark examine in R&D?

In scope: eight large research-based pharma-

The 2021 Antimicrobial Resistance Benchmark examines the antibacterial and anti-

ceutical companies

fungal pipelines of eight large research-based pharmaceutical companies. By vol-Country

ume and value of sales, these are the largest players in the global market for antibacterial medicines that are active in innovative R&D today. The Benchmark com-1

Company

HQ

GlaxoSmithKline plc

GBRpares the size and quality of their R&D pipelines. It also looks at the steps these2

Johnson & Johnson

USAcompanies are taking to ensure new medicines can be made accessible swiftly yet

3

Merck & Co, IncUSA

responsibly for people living in low- and middle-income countries (LMICs), where4

Novartis AG

CHE

rates of resistance are highest.

5

Otsuka Pharmaceutical Co, Ltd

JPN

As antimicrobials underpin treatment regimes in many areas of health, these6

Pfizer Inc

USA

companies have both a business interest in, and a public health responsibility

7

Sanofi

FRA

toward, antimicrobial R&D. Furthermore, they have the scale, resources and exper-

8

Shionogi & Co, Ltd

JPN

tise to support antimicrobial R&D in other ways, for example by partnering with or
acquiring smaller companies to help advance their candidates.
Most antibacterial and antifungal R&D is currently being carried out by smalland medium-sized enterprises: 75% of the antibacterial and antifungal R&D pipelinetargeting priority pathogens is being developed by such companies. Yet these companies generally lack the financing and other resources, such as regulatory expertise, to commercialise new products. While partnerships with larger companies canhelp secure the resources they need, several small drugmakers are turning to local
companies based in emerging economies, mainly China, to reach global markets.1

Priority pathogens:designated by WHO and CDC
Gram-negative bacteria▲* Acinetobacter spp.
B. pertussis
Campylobacter spp.
▲ Enterobacteriaceae
E. faecium
H. influenzae type B

Which are the pathogens in scope?
The Benchmark focuses on R&D projects that target the priority bacteria and fungi
identified by WHO2 and the CDC3 as being of particular concern due to drug resistance, for which there is an urgent global need for new treatments.*** There arethree levels of prioritisation in the WHO priority list: critical, high, and medium, andfour levels of threat in the CDC list: urgent, serious, concerning and watch. Six ofthe pathogens fall into one or other of these prioritisation categories, including
Candida auris, one of only two fungal pathogens on either list. Many strains of C.
auris are proving resistant to all three existing classes of antifungal medicines.

H. pylori
M. genitalium▲ N. gonorrhoeae▲ P. aeruginosa
Salmonella spp.
Shigella spp.
Gram-positive bacteria▲ C. difficile
Enterococcus spp.
S. aureus
Group A Streptococcus
Group B Streptococcus
S. pneumoniae
Tuberculosis
M. tuberculosis
Fungal pathogens
A. fumigatus▲** Candida spp.
▲ = Priority pathogens deemed by WHO and the
CDC to pose the highest level of concern due todrug resistance (‘critical’ and/or ’urgent’, respectively). Specific resistance profiles can be found in
Appendix V.

TH E E X AM PLE O F E . CO LI : WH Y N E W TR E ATM E NTS AR E U RG E NTLY N E E D E D
E. coli, a member of the

UTIs are more dangerous for

The antibiotic ciprofloxacin is

E. coli is a gram-negative bac-Enterobacteriaceae family, is apeople with diabetes and thoseoften used to treat UTIs, but

terium, which possesses a dual

frequent cause of urinary tract

undergoing cancer treatment.4,5

resistance is rising – among E.

membrane envelope, making

infections (UTIs). These arecoli infections, resistance rates

it a challenging target foramong the most common infec-

range from 8.4% to 92.2%.6

research into new antibiotics.

tions worldwide, affecting 1 in

The Benchmark identified three

2 women at some point in their

medicine candidates in clinicallives.

development targeting E. coli
infections specifically.

* Acinetobacter baumanii is the species
designated as a critical/urgent priority.
** Candida auris is the species designatedas a critical/urgent priority.

*** I.e., those bacteria and fungi that wereidentified and prioritised by the WHO in
its 2017 Global Priority List of AntibioticResistant Bacteria, and the CDC’s 2019
Antibiotic Resistance Threats report. See
Appendix V.

28

Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT – PI PE LI N ES

Sustained involvement in antimicrobial
R&D from seven out of eight companies
Collectively, the companies evaluated have 92 active medicine and vaccine projects that target infections caused by priority bacteria and fungi. Almost a thirdof projects target M. tuberculosis, which accounts for the bulk of drug-resistant infections worldwide. A further third target gram-negative bacteria, mainlyEnterobacteriaceae. The majority of projects aim to develop new medicines (62 outof 92). Novartis is the only company evaluated that is not currently active in R&D
targeting priority pathogens. The remaining seven companies have sustained theirinvolvement in antimicrobial R&D. Several companies have expanded their pipelines since the 2020 Benchmark report was published. Pfizer and GSK stand out for
expanding their pipelines by five and four projects, respectively. GSK leads in R&D,
with 31 R&D projects, about half of them vaccines, and including two novel medicine candidates in clinical development. Eleven of its projects target pathogens that
WHO and CDC place in the highest risk categories due to AMR.
FIGURE 23. Eight innovative medicines and six innovative vaccines in clinical development
Out of the 36 projects in clinical stage, most (22) aim to expand the use of an existing medicine or
vaccine to more indications or populations. There are 14 clinical-stage projects that aim to bring new/innovative candidates to the market.

Post-clinical*

Clinical development(Phase I-III) and recent
approvals

5
92
projects

Innovative medicines
8

36

36
projects in
Phase I-III

51

Innovative vaccines

622

Adapting existing
medicines and vaccines

Discovery andpreclinical stage* Post-clinical stages of development(Phase IV or technical lifecycle)

FIGURE 24. How large are the companies’ pipelines – and how far along are the projects?
Of the eight companies assessed, GSK has the largest R&D pipeline targeting bacteria and fungi inscope. 19 out of 31 projects in their pipeline (61%) are in discovery/preclinical stage.
Total
GSK

0

9

Johnson & Johnson 0

10

3

2

31

4 1 1

14

5 1 1

4

13

2

13

0

Pfizer

0 1

4

3

3

Shionogi

0

5

2 1

3

Sanofi0

Otsuka0 1 1 1 1

Novartis

0 0
0

2 1 1

2

8

MSD

2

5

11
6

2

4

MSD gained four regulatory approvals during theperiod of analysis, including relebactam/imipenem/
cilastatin (Recarbrio™).
This antibiotic can be used
to treat a range of serious
hospital acquired infections, including bacterial
pneumonia.

010
Discovery

Preclinical20
Phase I

Phase II

Phase III30
Projects
Approval

Post-clinical** Post-clinical stages of development(Phase IV or technical lifecycle)

29

Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT – TARG ET PATHOG E NS

Which pathogens are receiving mostattention?
Gram-positive bacteria: empty

Gram-negative bacteria: projects focus on

pipelines for high-risk pathogens

pathogens posing most serious threat

The pipeline for gram-positive bacteria is

Continuing the trend found in 2020, most of the medicine

skewed towards vaccine development, which

projects that address gram-negative bacteria target theaccounts for 15 of the 21 projects. These most

most critical and urgent threats (27 out of 35)These path-frequently target S. pneumoniae. There is currently no medicine candidate in the pipeline tar-sistant Enterobacteriaceae, or CRE, and extended-spec-2

geting this pathogen. The medicines in early-stage development are limited to a hand-ogens are: Enterobacteriaceae (including carbapenem-re-

Undeterminedtrum beta-lactamase (ESBL)-producing Enterobacteriaceae),

21

P. aeruginosa (including carbapenem-resistant and mul-

ful of projects against S. aureus. There is a lack35

92

of medicines for C. difficile, seen as an ‘urgent’

Acinetobacter spp. The projects targeting these pathogens

projects

threat by the CDC, or for Enterococcus spp.,

include two recently approved medicines: relebactam/imi-

seen as a ‘high’ priority by WHO and a ‘serious’threat by the CDC.

tidrug resistant P. aeruginosa) and carbapenem-resistantpenem/cilastatin (Recarbrio™), from MSD, and cefiderocol

30

4(Fetroja®/Fetcroja®), from Shionogi. The only vaccine targeting these three pathogens is Johnson & Johnson’s ExPEC9V,

Tuberculosis targeted by one third ofwhich targets extraintestinal pathogenic E. coli.

projects

The remaining gram-negative pathogens in scope (8) are tar-

The projects targeting M. tuberculosis represent

geted by just a handful of projects. This includes Sanofi’s
Shan6™ vaccine for the prevention of H. influenzae and B.

almost one third of the pipeline, with medicines
accounting for 29 of the 30 projects. There is

4 R&D projects target fungi

pertussis, and some discovery/preclinical projects target-

only one tuberculosis vaccine in development by

There are currently four projects inting Salmonella spp. and Shigella spp. For some gram-nega-

the companies in scope: GSK’s M72/AS01E, cur-development against fungal path-tive pathogens in scope, there are no products in the pipeline:

rently in Phase II. Most of the eight companies

ogens in scope (Candida spp. andCampylobacter spp., H. pylori (both categorised as high pri-evaluated are active in tuberculosis R&D.

A. fumigatus). All are in discov-

orities by WHO) and M. genitalium (on the watch list of theery stage, except fosmanogepix, aCDC).

potential first-in-class antifungal in
Phase II development by Pfizer.

PROMISING CANDIDATESPFIZERSHIONOGI

Fosmanogepix

Cefiderocol (Fetroja®/Fetcroja®)

Phase II

Recently approved

Fosmanogepix is potentially a first-in-

Cefiderocol is a siderophore ceph-

gramme is still ongoing. In order to makeclass antifungal medicine for the treat-

alosporin indicated for the treat-cefiderocol more accessible, Shionogi

ment of invasive fungal infections, including resistant strains.7 The ongoing Phase

ment of gram-negative bacterial infections8 which obtained first approval inreports discussions with generic medi-

II trial is testing fosmanogepix’s efficacy

November 2019 from the FDA. EMA

ogy transfer options to bring cefiderocol

against invasive mold infections caused byapproval was granted in April 2020.

to geographies that their current distri-

C. auris or other filamentous fungi.

Stewardship & Access plan: Shionogi

bution networks do not reach. In July

Stewardship & Access plan: In

has successfully applied for cefidero-

2021, Shionogi, the Global Antibiotic

April 2021, Pfizer acquired Amplyx

col to be included in the WHO’s Model

Research and Development Partnership

Pharmaceuticals Inc., and with it fos-

List of Essential Medicines (EML), and(GARDP) and the Clinton Healthmanogepix. Pfizer will continue the clin-it has now been placed in the Reserve

Access Initiative (CHAI) announced aical development of this antifungal as

category of antibiotics. Shionogi has

Memorandum of Understanding (MOU)

well as the Expanded Access Programme

expressed its intention to conduct sur-to accelerate the delivery of access tothat Amplyx Pharmaceuticals Inc. had

veillance for cefiderocol.

cefiderocol, including in low- and mid-put in place.

Cefiderocol’s compassionate use pro-cine manufacturers on potential technol-

dle-income countries.930

Research & Development – Target pathogens

Antimicrobial Resistance Benchmark 2021

Are projects targeting the most critical and urgent pathogens?
The pathogens targeted most frequently by the eight companies are: CR-/ESBL-

FIGURE 25. One third of pipeline targets

producing Enterobacteriaceae (14 unique products) and P. aeruginosa (8 uniquepathogens in highest risk categories

products). Within the Enterobacteriaceae family, the focus is on E. coli and

WHO and CDC each categorise pathogens into

Klebsiella pneumoniae.

multiple tiers to determine the level of risk from

Six of the eight companies in scope are developing candidates to target these
critical/urgent pathogens, including 18 projects in clinical-stage development or

AMR. The highest risk categories are ‘critical’ and‘urgent’ respectively.

recently approved. GSK leads in this area followed by Pfizer and Shionogi. These
three companies have increased the number of their projects targeting critical andurgent priorities since the last iteration of the AMR Benchmark. Three companies

Other priority
pathogens

Critical/Urgent
pathogensare developing vaccines targeting pathogens categorised as critical and/or urgent:
GSK (C. difficile and N. gonorrhoea), Johnson & Johnson (E. coli) and Pfizer (C.
difficile).

59

92
projects

33

Few vaccine projects for gram-negative pathogens
Approximately one third of the pipeline comprises vaccine R&D projects.
Vaccines are a critical tool for preventing the spread of infectious diseases, andthereby the development and spread of AMR. Overall, S. pneumoniae followed
by Enterobacteriaceae are targeted by most vaccine candidates in the pipeline.
However, very few vaccine candidates target other gram-negative pathogens in
scope. This leaves some concerning gaps, such as for A. baumannii, an opportunistic pathogen that is associated with hospital outbreaks, as well as for P. aeruginosa.

Critical/Urgent pathogen• CR/ESBL-producing
Enterobacteriaceae• Carbapenem-resistant A. baumannii• Carbapenem-resistant P. aeruginosa• Drug-resistant N. gonorrhoeae• C. diﬃcile• C. auris

Projects
19
4
11
3
3
3

Both placed by WHO and CDC in the highest risk categories.
Six of the companies evaluated are developing vaccines (30) for the pathogens in scope. Shionogi is new to this group in 2021, having entered a collabora-

FIGURE 26. One third of the pipelinetion with HanaVax to develop a vaccine against S. pneumoniae. GSK is developing

comprises vaccines R&D projects

16 vaccines, more than any other company. It is followed by Pfizer, with four. BothOf the 30 vaccine candidates, 20 are innovative

have clinical-stage vaccine candidates targeting C. difficile. These are the only clin-candidates, and 10 aim to establish effectivenessical-stage vaccine candidates, alongside GSK’s Bexsero (targeting N. gonorrhoeae)

against additional pathogens or serotypes.

and Johnson & Johnson’s ExPEC9V vaccine (targeting E. coli) targeting pathogens
Vaccinesin the critical and/or urgent categories.
PROMISING CANDIDATES

Medicines

30

PFIZER

GSK

C. difficile vaccine (PF-06425090)

M. Tuberculosis prophylactic vaccine

Phase III

M72/AS01E (GSK692342)

This innovative vaccine in Phase III

Phase II

would represent the first available vac-

This innovative vaccine currently incine against C. diﬃcile, a pathogen cate-Phase II trials shows up to 50% effi-

gorised as an urgent threat by the CDC.

cacy in the prevention of tuberculosis inThis pathogen causes diarrhoeal disease.

adults, which is high compared to rates

Severe, life-threatening cases present

achieved by other candidates.11

mostly in older patients.10
Stewardship & Access plan: Assuming

Access plan: In 2020, GSK licensed

regulatory and clinical success, Pfizer

Medical Research Institute (Gates MRI).

would seek to register the product in

The Gates MRI now leads the candidate

countries with the highest local burden

development and will sponsor futureof disease and explore equitable pricing

clinical trials, while GSK will provide thestrategies. Given the lack of data in many

AS01 adjuvant. This agreement increases

countries, particularly LMICs, Pfizer isthe likelihood that the candidate is opti-

conducting real world data research

mised for use in low-income coun-studies in several LMICs to strengthentries and that it is available shortly after

its understanding of burden and unmet

approval in countries with a high burden

need and better assess current burdenof tuberculosis.

92
projects
62

the vaccine to the Bill & Melinda Gates

of disease.

31

Research & Development – Target pathogens

Antimicrobial Resistance Benchmark 2021

TABLE 2. 92 medicine and vaccine projects target priority bacteria and fungi
The figure shows how many products are in discovery/preclinical stages and which ones are in clinicaldevelopment from the eight companies in scope. The pathogens receiving the most attention include
Enterobacteriaceae, S. aureus, S. pneumoniae and M. tuberculosis.
PathogenPriority/threat level

Medicines

WHO

Early stages* Phase I

CDC

Vaccines
Phase II

Phase III

Approval

Early stages* Phase I

4 FimH
Avycaz®/(GSK3882347) Zavicefta®
(neonates)[GSK][Pfizer]**;aztreonam+ avibactam[Pfizer]

Recarbrio™
[MSD]

3

Phase II

Phase III

Approval

GRAM-NEGATIVE BACTERIAEnterobacteriaceae Critical Urgent/(CRE/
Serious
ESBL-producing)

Fetroja®/

Fetcroja®
(paediatric)[Shionogi]

Acinetobacter spp.

Critical Urgent

P. aeruginosa

Critical Serious

5

gepotidacin[GSK]

ExPEC9V[Johnson &Johnson]Fetroja®/
Fetcroja®
[Shionogi]

Fetroja®/
Fetcroja®
(paediatric)[Shionogi]

Fetroja®/
Fetcroja®
[Shionogi]

Avycaz®/Zavicefta®
(paediatric)[Pfizer]**;Fetroja®/
Fetcroja®
[Shionogi]

Fetroja®/
Fetcroja®
(paediatric)[Shionogi]
N. gonorrhoeae

High

UrgentCampylobacter spp. High

Serious

Salmonella spp.

High

SeriousH. pyloriHigh

H. influenzae

Medium

Shigella spp.

Medium Serious

B. pertussis

Watch

M. genitalium

Watch

gepotidacin[GSK]

Bexsero [GSK]3
Shan6™
[Sanofi]1

2
Shan6™
[Sanofi]

GRAM-POSITIVE BACTERIAEnterococcus spp.

High

Serious

S. aureus

High

SeriousS. pneumonia

Medium Serious

Sivextro®
(paediatric)[MSD]
3

Sivextro®
(paediatric)[MSD]

Teflaro®/Zinforo®
(neonates)[Pfizer]**

1 GSK3878858A
[GSK]

1

Skypac®
(Sanofi)
V116 (MSD)

C. difficile

UrgentGr. A. Streptococcus

Concerning

Sivextro®
(paediatric)
[MSD]

1

Gr. B. Streptococcus

Concerning

Sivextro®
(paediatric)
[MSD]

1

GSK2904545A[GSK]

Dificid®

(paediatric)[MSD]

Prevnar20™
(paediatric)[Pfizer]Vaxneuvance™
[MSD]
Prevnar20™
(adult) [Pfizer]

PF-06425090[Pfizer]

PF-06760805[Pfizer]

TUBERCULOSISAMR
Serious
R&D
priority20

GSK-070 (GSK- Rifapentine
Sirturo®
3036656)(new regimen) (paediatric)[Johnson &[GSK][Sanofi]Johnson]
OPC-167832
Deltyba® (pae[Otsuka]
diatric) [Otsuka]
rifapentine +isoniazid (paediatric) [Sanofi]

Candida auris

Urgent2

fosmanogepix[Pfizer]

Candida spp.

Serious2Aspergillus
fumigatus

Watch

2

M. tuberculosis

M72/AS01E
[GSK]

FUNGI

■ There are no projects in the pipeline targeting the pathogens highlighted in grey.
Projects are included for each pathogenthat they target, which means some projects are included more than once. Details
about specific resistance profiles are in
Appendix V.

Adaptations of commercialised products
are named with their brand name.
Not all projects disclosed to the
Benchmark are included in this table due
to confidentiality agreements.

*This column displays the number of projects in discovery and preclinical stages ofdevelopment.
** Teflaro® and Avycaz® are marketed byAllergan in the USA.

32

Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT – CHANG ES SI NCE 2020

R&D pipeline grows slightly, with mostcompanies contributing new projects
With resistance building and medicines becoming less effective, promising clinicalcandidates are closely watched to see whether and when they are likely to become
available. This section examines how the number of R&D projects targeting priority pathogens has changed since the previous analysis,* looking specifically at eightlarge research-based pharmaceutical companies active in priority pathogens R&D.**
Since the previous Benchmark analysis, 22 projects have left the pipeline, for reasons such as project discontinuation or divestment. But there have been 38 additions to the pipeline. Overall, balancing the 22 projects that have left and the 38
additions, the pipeline has seen a modest increase in size: from 77*** projects to 92(net increase of 15 projects).
Although the size of the pipeline overall remains small, this upward movement
perhaps signals a stabilisation of activity in this area of R&D by large researchbased pharmaceutical companies.
Furthermore, one third (18) of the 54 projects that remained in the pipeline fromthe 2020 analysis have progressed to the next stage of development.** Whether an
R&D project progresses along the pipeline depends on multiple factors, including
the specific disease being targeted as well as other practical challenges.
Of the 38 new projects that entered the pipeline, 25 are innovative medicinesand vaccines. These are important because they may constitute new chemicalclasses of medicines or incorporate new technologies in vaccine development, andsuch innovations may prove critical in curbing antimicrobial resistance in the years
to come.

FIGURE 27. R&D pipeline for priority pathogens has grown from 77 to 92 projects

FIGURE 28. Most new projects are innovative

The eight large research-based companies in scope have added 38 new R&D projects to

Of the new projects that entered the pipeline in this analysis,

the pipeline since the previous analysis. There are now 92 projects,*** including some thatmost aim to develop a new product (‘innovative’), rather thanhave recently gained marketing approval, targeting the pathogens that pose the greatest

establish whether existing ones are also effective for treatingrisk from antimicrobial resistance.

additional populations or conditions (‘adaptive’).
Left pipeline due tomarket approval

Discontinued*
2020

22

Adaptive

Innovative

1 77

2021

54
Continued
from 2020*

38 92
New projects in thepipeline for 2021

9

2021

38
New projects in thepipeline for 2021

* Since the previous Benchmark analysis,
published in January 2020, which covered
projects active between 9 September
2017 and 21 June 2019.

38
new projects

23

Left pipeline due tomarket approval

Discontinued*
2020

15

14 77
54

92

Continued
from 2020** R&D projects from the nine small andmedium-sized enterprises that were also
assessed in the previous AMR Benchmark
report have been removed from the analysis to allow for comparison.

*** This analysis looks at projects active
since 22 June 2019 and up until 30 April
2021.

33

Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT – N EW M E D ICI N ES

Eight clinical-stage projects aim to develop
completely new treatments
The 2021 Benchmark has identified eight clinical-stage antibacterial and antifungal

PROMISING CANDIDATES

R&D projects that aim to bring to market new chemical entities or new fixed-drug
combinations. The hope is that such new treatments are sufficiently different from

GSK3882347

those agents already on the market that pre-existing mechanisms of resistance will

GSK

not impair their effectiveness. As such, they are some of the most important pro-This non-traditional antibacterial medi-

jects to watch in the antimicrobial pipeline.

cine is currently in Phase I. It inhibits the

These eight projects comprise four antibacterials, two antituberculosis med-

E. coli adhesive protein, FimH, thus pre-icines, one antifungal medicine, and one disclosed on condition of confidential-

venting infection by impeding the binding of E. coli to the bladder wall.12 It isity. Three of them meet some or all of the innovativeness criteria set by WHO* toidentify candidates with high value to combat resistance, for example because they
have a new mechanism of action against the target pathogen.14 The remaining fiveindicated for the prevention and/or

projects, such as fosmanogepix, which potentially represents a new class of antifun-of the Enterobacteriaceae family. Somegal, do not fall within the scope of WHO’s assessment of innovativeness, yet could

members of this family are resistant toalso provide major therapeutic advances if they reach the market.

nearly all antibiotics.

treatment of UTIs caused by E. coli, part

The eight projects identified here, if successful, could bolster the antimicrobials arsenal in a few years. Almost all have reached Phase II of development, which is

OPC-167832

when pharmaceutical companies are expected to start planning how they will bringOTSUKAthe new products to people living in low- and middle-income countries, as well as

This is a novel carbostyril derivative withhow they plan to safeguard the effectiveness of these medicines with the appropri-

antituberculosis activity as a DprE1 inhib-

ate stewardship measures. Looking across all clinical-stage projects, GSK, Otsuka

itor.13 This molecule meets all WHO

and Pfizer are among the companies that most comprehensively develop suchinnovativeness criteria. It is currently inplans.

Phase II for the treatment of uncomplicated pulmonary tuberculosis in adults.

TABLE 3. Potential game-changing antimicrobials in the pipeline
The table includes two recently approved** medicines and five innovative
medicine candidates in clinical development, from five of the eightcompanies evaluated. An eighth project is not listed, as it was disclosed onEnterobacteriaceae (CRE)
Relebactam/imipenem/ First marketing authorisationcilastatin (Recarbrio®)
obtained on 16
July 2019

Target pathogen(s)Shionogi

Cefiderocol (Fetroja®/
Fetcroja®)

First marketEnterobacteriaceae (CRE);
ing authorisation Pseudomonas aeruginosa (CRPA);
Acinetobacter baumannii (CRAB)
obtained on 14
November 2019

No cross-resistance

Candidate medicine StageMSD

New target

New drug classCompany

New mode of action

condition of confidentiality.

GSK

Gepotidacin

Phase IIIEnterobacteriaceae - E. coli●

GSK

GSK-070 (GSK-3036656) Phase II

Mycobacterium tuberculosis

●

●

●

●

OtsukaOPC-167832

Phase II

Mycobacterium tuberculosis

●

●

●

●

PfizerFosmanogepix***

Phase II

Candida auris;
A. fumigatum;
Fusarium spp.;
Scedosporium spp.

N/A N/A N/A N/A

GSKFimH (GSK3882347†)

Enterobacteriaceae - E.coli

N/A N/A N/A N/A* The four WHO-defined innovativenesscriteria for investigational clinical antibacterial candidates are: new chemical class(or structure); new target; new mode ofaction; and absence of cross-resistance.

Phase I** Approved during the period of analysis:
from 22 June 2019 to 30 April 2021.
*** As an antifungal, fosmanogepix is notin scope for WHO’s Clinical Antibacterial
pipeline, but it is considered a potential
new class of antifungal.

●† This projects is listed in WHO’s Clinical

Antibacterial pipeline 2020 as a non-traditional approach.

34

Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT – APPROVALS

Two new antibacterials and three nextgeneration vaccines reach the market
Six of the eight large research-based companies in scope have products thatreceived approvals and/or label extensions between the start of the period of analysis, 22 June 2019, and the end of the period of analysis, 24 September 2021. Asin the 2020 Benchmark, the majority of these approvals apply to antibacterials
already in the market and aim to extend the indications and/or target populationsof those products. There have been just two medicines and three vaccines thatreceived first approval since the previous Benchmark analysis. No antifungal medicine has been approved since the start of the Benchmark research programme in2017. Overall, seven approvals were extensions to allow existing medicines to be
used to treat adolescent, paediatric and neonatal patients.
The two medicines that received approval in this Benchmark are: Shionogi’s
cefiderocol (Fetroja®/Fetcroja®) and MSD’s relebactam/imipenem/cilastatin (Recarbrio™). These target Enterobacteriaceae, a family of bacteria for which
new medicines are urgently needed. Only one other new antibacterial has been
approved by the US Food & Drug Administration (FDA) during the period of analysis: lefamulin (Xenleta®) from Nabriva (not in scope).
MSD gained the most approvals: the one mentioned above, one first approval fora vaccine and two label extensions. Shionogi obtained approval for its antibacterial
cefiderocol from both the FDA and the European Medicines Agency (EMA).
TABLE 4. Newly-approved products and label extensions for products already on the market
The table shows the new approvals and label extensions received by the companies in scope for
products targeting priority bacteria and fungi between the start of the period of analysis for the 2020
AMR Benchmark (22 June 2019) and 24 September 2021.
Product name (brand name)Company

Priority pathogen(s)targeted

Target population

Indication

Approval date bystringent regulatory authority

NEW ANTIBACTERIAL MEDICINES IN THE MARKET
Cefiderocol (Fetroja®/Fetcroja®)

ShionogiEnterobacteriaceae; P.
aeruginosa

Adults (18+)

Complicated urinary tract infections (cUTIs), including
pyelonephritis

14-Nov-19, FDA

Relebactam/imipenem/cilastatin(Recarbrio™)

MSD

Enterobacteriaceae

Adults (18+)

Complicated Urinary Tract Infections (cUTI), including
pyelonephritis; Complicated Intra-abdominal Infections(cIAI);

16-Jul-19, FDA

SUPPLEMENTAL APPLICATIONS AND LABEL EXTENSIONS TO PREVIOUSLY APPROVED ANTIBACTERIAL MEDICINES
Bedaquiline (Sirturo®)

Johnson &JohnsonM. tuberculosis

Adolescent (12-<18 years)
and paediatric (5 - < 12 years)

Tuberculosis; MDR-TB

9 Aug 19 and
27 May 20, FDA

Cefiderocol (Fetroja®/Fetcroja®)

ShionogiEnterobacteriaceae; P.
aeruginosa; A. baumannii

Adults (18+)

Gram-negative bacterial infection (aerobic)

23 Apr 20, EMA

Enterobacteriaceae; P.
aeruginosa; A. baumannii

Adults (18+)

Hospital-acquired Bacterial Pneumonia/Ventilatorassociated Bacterial Pneumonia (HABP/VABP)

25 Sep 20, FDA

Ceftaroline fosamil (Teflaro®/
Zinforo®)*PfizerS. aureus

Neonatal (birth to less than 2months of age)Complicated skin and soft tissue infections (cSSTI)

13 Sep 19, FDA

Delamanid (Deltyba®)

OtsukaM. tuberculosis

Paediatric (>=30 kg) and paediatric (>=10 kg)

Tuberculosis; MDR-TB

17 Sep 20 and
22 Jul 21, EMA

Fidaxomicin (Dificid®)

MSD

C. difficile

Paediatric (6 months - 18
years old)

C. difficile-associated diarrhea (CDAD)

24 Jan 20, FDA

Relebactam/imipenem/cilastatin(Recarbrio™)

MSD

Enterobacteriaceae

Adults (18+)

Hospital-acquired Bacterial Pneumonia/Ventilatorassociated Bacterial Pneumonia (HABP/VABP)

04 Jun 20, FDA

Ceftazidime + avibactam (Avycaz®/
Zavicefta®)*

PfizerGram-negative bacteria

Adults (18+)

Bacteremia

25 Jun 20, EMA

Paediatric (3 months andolder)

Complicated intra-abdominal infection (cIAI);
Complicated urinary tract infection (cUTI), including
pyelonephritis; Hospital-acquired pneumonia (HAP),
including ventilator associated pneumonia (VAP)

17 Sep 20, EMA

NEW VACCINES
Pneumococcal 15-valent Conjugate
Vaccine (Vaxneuvance™)

MSD

S. pneumoniae

Adults (18+)

Pneumococcal disease

16 Jul 21, FDA

Pneumococcal 20-valent Conjugate
Vaccine (Prevnar20™)

PfizerS. pneumoniae

Adults (18+)

Pneumococcal disease

10 Jun 21, FDA

Shan6™

SanofiH. influenzae; B. pertussis

PaediatricDiphtheria; Haemophilus infections; Hepatitis B;
Pertussis; Poliomyelitis; Tetanus

May 21, Indian Regulatory Authorities

35*Teflaro® and Avycaz® are marketed byAllergan in the USA.

Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT – STEWARDSH I P & ACCESS PL ANS

In R&D, increased access and stewardshipplanning for medicines and vaccines
By planning ahead while a product is still in clinical development, pharmaceuti-

Scope of the analysis

cal companies can provide swifter access to new products at affordable prices, andThe 2021 Benchmark has assessed whether thehave measures in place from day one to ensure new products are used appropriately (known as stewardship). Phase II of clinical development is widely agreed bystakeholders as the point where such planning should start.
Looking at the pipelines of the eight companies in scope, almost all of the medicine candidates that have reached Phase II or beyond are now supported by bothstewardship and access plans. This is a significant improvement since the publication of the 2018 AMR Benchmark, when only a handful of candidates were supported. The companies’ vaccine projects are now also all covered by access plans(stewardship is not a primary concern for vaccines).
Overall, 18 out of the 20 late-stage medicine projects in this analysis have botheight large research-based companies in scope
for the R&D Research Area have access andstewardship plans in place for late-stage candidates (phase II and beyond), how detailed they
are and how broadly they are applied.
As with other analyses in this Research Area, theBenchmark focuses on R&D projects that target
the priority bacteria and fungi identified by WHO
and the CDC as being of particular concern due
to drug resistance, for which there is an urgent
global need for new treatments.

access and stewardship plans in place, confirming a trend suggested in the 2020
Benchmark, when the number of projects with both access and stewardship plansrose from two to four. All 11 late-stage vaccine projects have access plans in 2021, afurther improvement since 2020, when eight of 12 vaccines had access plans.
There remain big differences in companies’ approaches to access and stewardship and how comprehensive their plans are. However, some companies have added
more breadth to their portfolio-wide policies on access and stewardship planningsince the previous Benchmark. Most companies report project-specific access andstewardship plans for at least some of their projects in late-stage development.
The best examples identified by the Benchmark now include a more comprehensive
range of access and stewardship measures. Companies are making use of strategies
such as affordability frameworks, technology transfers to generic medicine manufacturers, WHO prequalification applications, compassionate use programmes,
and the expansion of registration filings, as well as implementing other access provisions stipulated in contractual agreements with funders and partners (e.g., theGlobal Drug Facility, the Bill & Melinda Gates Foundation, Wellcome Trust, and Gavi,
The Vaccine Alliance).

FIGURE 29. More stewardship and access plans for late-stage projects
In 2021, both the medicine and the vaccine late-stage pipelines show anincrease in the number of projects with plans to ensure swift access to
successful products and to ensure good stewardship of medicines.
Medicines R&D projects
2020

4

6

3

2021
0

5

10

15

Access and stewardship plans

Access plans

18 1 120
Neither

Vaccines R&D projects
2020

8

2021
0

5
Access plans

4
11
10

15

20

No access plans

36Research & Development – Stewardship & Access Plans

Antimicrobial Resistance Benchmark 2021

Projects funded by organisations, such as the Bill & Melinda Gates Foundationand Wellcome Trust, that request access provisions in their contracts, tend to

FIGURE 30. Which projects are ready forhave stronger, multifaceted access plans. A working group of experts, led bystewardship and access plans?

Wellcome Trust and including the Access to Medicine Foundation, have releaseda Stewardship and Access Plan (SAP) Development Guide15 that sets out practical

A total of 31 projects are in late-stage clinicalactions that pharma companies and product developers can take to develop robust

These projects have reached the stage whereplans early on. The Combating Antibiotic-Resistant Bacteria Biopharmaceuticalcompanies are expected to start developing

Accelerator (CARB-X) now requires now requires that all grant recipients com-

access and stewardship plans.

development and target the pathogens in scope.

mit to creating a SAP within 90 days of their product entering pivotal clinical trials (Phase III). Further, grantees are expected to develop a strategy to monitor theeffectiveness of such plans.

Antibacterials
Antifungals

6

Vaccines

Among the medicine projects with the most robust plans are Otsuka’s OPC-

5

9

1
4
0

167832 and its paediatric adaptation of the anti-tuberculosis medicine delamanid(Deltyba®). For the latter, Otsuka is building on its experience gained when bringing

45

Phase II

3
10
Phase III

15

20

Approved

the adult version of delamanid to market and is taking steps to make the paediatric version rapidly available and suitably formulated for children. A 25mg paediatricdose of delamanid for children has received approval from the European Medicines
Agency (EMA). The company is partnering with the Global Drug Facility, generic
medicine manufacturers, and children-oriented organisations to develop routes foraccess, and is donating its product to research institutions to build on its applications. Otsuka’s OPC-167832 is also supported by robust access provisions, stipulated through a contractual agreement with the Bill & Melinda Gates Foundation,
which co-funds the development of this Phase II anti-tuberculosis candidate.
Also strongly supported by access and stewardship provisions is Pfizer’s aztreonam+avibactam. Pfizer has eight late-stage R&D projects targeting pathogens in scope, four medicines and four vaccines, the most of any company evaluated. Pfizer has added depth and specificity to its access and stewardship plans
since 2020, which now include a wide range of strategies to ensure access in lowand middle-income countries (LMICs). Pfizer implemented a new policy that went

TABLE 5. Access and stewardship plans cover a diverse range of strategies
The table shows the range of strategies that the eight companies are incorporating in their stewardshipand plans. The most appropriate strategies depend on the product in question – not all strategies areapprioriate for all products. Companies that have improved their efforts in access and stewardship

SanofiShionogi

PfizerMSD

OtsukaGSK

Access strategies

Johnson & Johnson

planning for antibacterial and antifungal medicines include Otsuka, Pfizer and Shionogi.

Registration

●

●

●

●

●

●

○

WHO Prequalification Programme

○

○

○

●

●

●

○

WHO Collaborative Procedure for Accelerated Registration

○

○

○

○

○

○

○

EMA Article 58

○

○

○

○

○

○

○

Responsible IP and licensing arrangements

●

○

○

●

●

○

○

Managed access programmes

○

●

○

●

●

○

●

Product donation programmes

○

●

○

○

○

○

○

Special importation waivers

○

○

○

○

○

○

○

Sustainable manufacturing and supply

○

○

○

●

●

●

○

Equitable pricing

●

●

○

●

●

●

○

●

●

●

●

●

○

●

Responsible promotion

○

○

○

○

○

○

○

Availability of companion diagnostics

○

○

○

●

○

○

○

Stewardship strategies Surveillance** For products for which these companies are able to make such diagnostics
available through its own initiatives or inpartnerships.

37

Research & Development – Stewardship & Access Plans

Antimicrobial Resistance Benchmark 2021

into effect in May 2020 stating that it will not enforce its patents in least developed countries (LDCs). Furthermore, its late-stage R&D medicine projects fallunder portfolio-wide stewardship plans, including initiatives for surveillance andresearch and education on AMR (via unrestricted grants). For its recently acquired
Phase II antifungal, fosmanogepix, Pfizer plans to continue the Expanded Access
Programme that Amplyx Pharmaceuticals Inc. had started.
Pfizer’s four vaccines are also among the better covered in terms of accessplans of the 11 vaccines in late-stage development included in this analysis. These
include Pfizer’s new pneumococcal 20-valent conjugate vaccine, Prevnar20™
(recently approved for adults), and its vaccines targeting C. difficile and GroupB Streptococcus. The latter is being co-funded by the Bill & Melinda Gates
Foundation.
Approved in India in May 2021, Sanofi’s Shan6™ vaccine was specifically developed for children in low- and middle- income countries. This vaccine targets six
pathogens, adding polio to the group of pathogens previously targeted by the company’s Shan5™ vaccine. Sanofi has a dedicated manufacturing facility in India, where
it applies supply-chain best practices including buffer and safety stocks. Additionalcountries in scope for registration include Thailand and Kenya, where there are
ongoing Phase III trials. For Shan6™, Sanofi has applied for WHO prequalification
to ensure access to the vaccine in all countries eligible for support from Gavi, The
Vaccine Alliance. Pooled procurement, for example via Gavi and UNICEF, is an effective route to ensure quality, supported by WHO’s prequalification process, and toenable countries to access a stable and affordable supply of vaccines. In addition,
Sanofi has developed equitable pricing strategies, conducted a payer pricing survey
in nine countries, and takes account of affordability by market type.
With strong company-wide policies for access and stewardship, GSK has fivelate-stage R&D projects targeting pathogens in scope, and reports having project-specific access plans for most of them. All five projects have ongoing trials in
LMICs. GSK does not conduct clinical trials in countries where it does not intend
to pursue registration and to make the product available for use. GSK reports thatit has developed an equitable pricing strategy framework for LMICs that applies
across its portfolio and business units. Its access plans include equitable pricing strategies, registration filings, non-exclusive licensing and supply chain commitments. GSK states that it does not file patents in LDCs or low-income countries nor does it enforce historic patents. GSK commits to conducting global surveillance studies for its new antibacterials to enable appropriate use and support
stewardship.
Johnson & Johnson has one vaccine (ExPEC9V) and one medicine in late-stage
development, the paediatric adaptation of the antituberculosis medicine bedaquiline (Sirturo®). They are both covered by project-specific access plans. The current stewardship activities ongoing for the adult indication of bedaquiline (Sirturo®)
will extend to the newly approved paediatric indication, for use in patients aged
5-12 years and weighing at least 15 kg. There are no clinical trials running for the
EXPEC9V vaccine in any of the 102 LMICs examined for this analysis, but Johnson& Johnson is planning to expand its Phase III trial to include LMICs.
Shionogi has progressed in this area by actively seeking out partners to
improve access to, and stewardship of, its recently approved antibiotic cefiderocol(Fetroja®/Fetcroja®). MSD does report a general commitment to improving access,through registration and affordability measures, and to ensuring stewardship, primarily through surveillance. Novartis does not have any R&D projects that are eligible for this assessment.

38

Research & Development – Stewardship & Access Plans

Antimicrobial Resistance Benchmark 2021

EXAMPLES OF GOOD PRACTICE IN STEWARDSHIP & ACCESS PLANNING
OPC-167832
OTSUKA

OPC-167832 is a novel carbostyril deriv-

Stewardship & Access plan: Otsuka

ative with antituberculosis activity as a

is partnering with the Bill and Melinda

DprE1 inhibitor. This molecule meets all

Gates Foundation in the development of

WHO innovativeness criteria. The project

this medicine and the access and stew-

is currently in Phase II for the treatment

ardship plans for this medicine are inof uncomplicated pulmonary tuberculo-alignment with the BMGF global access

sis in adults.

requirements.

Aztreonam/avibactam (PF-06947387)
PFIZER

Aztreonam/avibactam is a new

Stewardship & Access plans: Pfizer isden, including countries in Asia and thefixed-drug combination with activ-

conducting clinical trials in some LMICs.

Middle East among others.

ity against carbapenemase-producing

It will explore registration in countries

Enterobacteriaceae (CPE) with metal-

included in the clinical trials and otherslo-ß-lactamases (MßLs) with Phase III tri-

based on unmet need and disease bur-als ongoing in 11 LMICs.

Shan6™ Paediatric hexavalent vaccine DTP-HepB-Polio-Hib
SANOFI

Shan6™ is an hexavalent vaccine tar-

Access plan: Shan6™ vaccine is being

geting diphtheria, tetanus, B. pertus-

specifically developed for LMICs andsis, Hepatitis B, H. influenzae type b, andSanofi has applied for WHO prequalifica-

poliovirus.

tion to ensure access in countres eligible

Poliovirus was added to the 5 pathogens

for support from Gavi. Shan6™ will betargeted by the Shan5™ vaccine withproposed to Unicef through their tender

the aim to reduce the number of shots

procurement process and price setting

in children undergoing routine vaccina-

will take into account Gavi’s value-based

tion. Shan6™ is the only project in theassessment including five premium driv-

pipeline targeting H. influenzae. Phaseers. Sanofi has a dedicated vaccine facil-

III trials are ongoing in India, Thailand

ity in India that already successfully pro-and Kenya, with trials also planned induces Shan5™. Sanofi applies supply

Vietnam. Sanofi obtained marketing

chain best practices including buffer andauthorisation for Shan6™ in India in May

safety stocks and shortage mitigation

2021.

strategies.

Group B Streptococcus vaccine (PF-06760805)
PFIZER

There are ongoing Phase II trials in South

worldwide annually.16 Immunisation ofAccess plan: In 2016, Pfizer received

Africa for this innovative vaccine. Therepregnant women has the potential ofa grant from the Bill & Melinda Gates

is currently no vaccine against Group B

reducing morbidity associated with thisFoundation to conduct a Phase I-II clin-

Streptococcus (GBS), and the develop-

pathogen and reduce infant mortality as

ical trial of its vaccine candidate against

ment is known to be challenging.

well as maternal sepsis, stillbirths andGroup B Streptococcus infection inGroup B Streptococcus is a leading cause

preterm births.

lower- or middle-income countries andof neonatal and young infant sepsis andis working to develop the vaccine candi-meningitis, and it is particularly problem-

date for potential worldwide use.

atic in low-income countries. It is estimated to cause 90,000 infant deaths

39Antimicrobial Resistance Benchmark 2021

RESE ARCH & D EVE LO PM E NT

Looking ahead

With antimicrobial resistance on the rise and very few large research-based pharmaceutical companies still engaged in antibacterial and antifungal R&D, it is critical for companies to continue investing in, and developing, these fundamental medicines and vaccines. One lesson to be learnt from the ongoing Covid-19 pandemic isthat complex global issues can only be tackled through collaborative, coordinatedaction. The pharmaceutical industry, policymakers and investors all have a role toplay in ensuring R&D efforts address the highest priorities in the fight against AMR.

CO M PAN I ESG OVE R N M E NT S

Investments and pipeline• Foster a secure and sustainable market for antibiotics and• Remain engaged in antibacterial and antifungal R&D, andcontinue to develop new, innovative and adaptive medicinesand vaccines.
• Align investments with global health priorities and direct

antifungals and develop policies that encourage and incentivise companies to remain engaged in the R&D space.
• Explore new and innovative models, such as pilot programmes for antibiotic and antifungal procurement,

them towards critical and/or urgent ‘priority pathogens’. Be

delinked from volumes. Ensure selection criteria encour-alert and versatile in R&D, moving quickly when the WHOages responsible behaviour from companies.

and CDC update their priority lists to include emerging
threats.
• Expand focus of pipelines to also target those resistantpathogens for which R&D is limited.

I NVESTO RS• Acknowledge the materiality of AMR and significant risks
where untreatable drug-resistant infections could compromise profitable business lines (e.g., cancer medicines

Stewardship and access planning• Pursue stewardship and access planning for all late-stage
clinical projects for new medicines, both novel and adaptive.

and treatments). Engage to support companies in need ofinvestments.
• With new financial incentives for developers of novel anti-• In terms of vaccines, increase access planning and provide

biotics being piloted by some national governments, makeswift access to these products in low- and middle-income

use of opportunities that arise for secure investments incountries (LMICs). This could have significant impact oncompanies leading R&D.

curbing the development and spread of resistance.
• Increase the depth and breadth of access and stewardship plans – for example, by expanding schemes into new
countries, or by combining multiple types of strategies toincrease access to a particular product.
• Take into account the needs of populations in LMICs toensure new medicines are available in sufficient quantityand quality, and will be appropriately used.
• Ensure stewardship and access plans are inclusive of countries, especially low-income countries, with particularly highburdens of disease and vulnerable populations.

40

Antimicrobial Resistance Benchmark 2021

RE FE RE NCES
1. Biotechs are saving the world fromsuperbugs. Can they also save themselves? June, 2021
2. WHO. Global Priority List of
Antibiotic Resistant Bacteria to Guide
Research, Discovery, and Developmentof New Antibiotics.; 2017. doi:10.1590/
S0100-15742013000100018
3. Centers for Disease Control U.
Antibiotic Resistance Threats in the
United States, 2019.; 2019. www.cdc.gov/
DrugResistance/Biggest-Threats. html.
Accessed November 20, 2019.
4. National Cancer Institute. Urinary andBladder Problems. https://www.cancer.
gov/about-cancer/treatment/side-effects/urination-changes.Accessed April
22, 2021
5. Zasloff M. Why are diabetics prone to kidney infections? J Clin
Invest.2018;128(12):52135215. https://doi.org/10.1172/JCI124922
6. Health Policy Watch. The ‘Silent
Pandemic’ of Antimicrobial Resistance –Lessons Learned From COVID19. https://
healthpolicy-watch.newssilent-pandemic-antimicrobial-resistance. Accessed April
12, 2021

ria: CARB-X [website] Boston: Boston
University; 2021 (https://carbx.org/carb-x-news/carbx-announces-funding-for-gsk-to-develop-a-new-drugfor-urinary-tract-infections-uti-caused-by-escherichiacoli-bacteria/, accessed 23 January 2021).
13. Hariguchi N, Chen X, Hayashi Y, etal. OPC-167832, a Novel Carbostyril
Derivative with Potent
Antituberculosis Activity as a DprE1
Inhibitor. Antimicrob Agents Chemother.
2020;64(6):e02020-19. Published 2020
May 21. doi:10.1128/AAC.02020-19
14. 2020 Antibacterial agents in clinical and preclinical development: an
overview and analysis. Geneva: World
Health Organization; 2021. Licence: CC
BY-NC-SA 3.0 IGO.
15. Stewardship &amp; Access Plan (SAP)
Development Guide. 2021 [www.carbx.org/about/stewardship-and-access]16. Davies HG, Carreras-Abad C, Le DoareK, Heath PT. Group B Streptococcus:
Trials and Tribulations. Pediatr Infect Dis
J. 2019 Jun;38(6S Suppl 1):S72-S76. doi:
10.1097/INF.0000000000002328. PMID:
31205250

7. Shaw KJ, Ibrahim AS. Fosmanogepix:
A Review of the First-in-Class Broad
Spectrum Agent for the Treatment ofInvasive Fungal Infections. J Fungi (Basel).
2020 Oct 22;6(4):239. doi:10.3390/
jof6040239. PMID: 33105672; PMCID:
PMC7711534.
8. Zhanel GG, Golden AR, Zelenitsky S,
Wiebe K, Lawrence CK, Adam HJ, Idowu
T, Domalaon R, Schweizer F, Zhanel MA,
Lagacé-Wiens PRS, Walkty AJ, Noreddin
A, Lynch Iii JP, Karlowsky JA.
Cefiderocol: A Siderophore Cephalosporinwith Activity Against CarbapenemResistant and Multidrug-ResistantGram-Negative Bacilli. Drugs. 2019
Feb;79(3):271-289. doi:
10.1007/s40265-019-1055-2. PMID:
30712199.
9. GARDP, CHAI and Shionogi announce
MOU to increase access to antibiotic to treat antimicrobial resistant infections in low- and middle-income countries [Internet]. GARDP.
[cited 2021 Nov 9]. Available from:https://gardp.org/news-resources/
gardp-chai-shionogi-announce-mou/
10. Jump RL. Clostridium difficile infection in older adults. Aging health.
2013;9(4):403-414.doi:10.2217/ahe.13.37
11. Tait DR, Hatherill M, Van Der Meeren O,
Ginsberg AM, Van Brakel E, Salaun B et al.
Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis. N Eng J Med.
2019;381(25):2429–39 (https://pubmed.
ncbi.nlm.nih.gov/31661198/, accessed 5
August 2020).
12. CARB-X funds GSK to develop a
new drug for urinary tract infections(UTI) caused by Escherichia coli bacte-41Antimicrobial Resistance Benchmark 2021

42

Antimicrobial Resistance Benchmark 2021

CO NTEX T

Responsible Manufacturing

A huge number of manufacturing sites around the world are involved in the
production of antibacterials, with many based in India and China.1 If thesesites do not manage their waste appropriately, the discharge of wastewaters containing active pharmaceutical ingredients (APIs) into the environment may lead to the development of resistant bacteria, or the emergenceof new forms of resistance which existing medications cannot effectively
treat.2,3,4 It is therefore critical that companies take responsibility for, andare cautious about, their manufacturing processes.5,6Companies that operate manufacturing sites can reduce the risk of antimicrobial resistance (AMR) by implementing a robust environmental
risk-management strategy. This governs how sites manage and dispose ofwaste that potentially contains APIs, including by auditing and monitoring to ensure the levels of antibacterial residues present in wastewaters do
not exceed limits that are considered safe. Pharma companies can leverage their positions in the supply chain to raise standards at suppliers’ sites
by requiring them to meet specific limits, and by extending those standards to the waste treatment plants they contract to dispose of manufacturing waste.
Companies and products in scope
Seventeen pharmaceutical companies – made up of 8 large research-based companies and 9 generic medicine manufacturers – are in scope for the 2021 AMR
Benchmark, with a combined total of 801 antibacterial products.
Manufacturing sites in scope
The Benchmark examines the pharma companies’ policies and practices withregards to a combined total of 1,057 antibacterial manufacturing sites, based ondata reported by the companies.* Together, their antibacterial manufacturing sites
consist of:• 93 sites operated directly by large research-based companies• 94 sites operated directly by generic medicine manufacturers• 870 sites operated by third-party suppliers to the companies in scope
FIGURE 31. Majority of manufacturing sites in this analysis are operated by suppliersThis figure shows the number of sites in scope of the analysis, broken down by whether they areoperated by large research-based companies, generic medicine manufacturers, or third-party suppliers.
Sites operated by:Large research-based companies

93

Generic medicine manufacturers

94

Third-party suppliers0* No data on directly-operated sites isavailable for two companies: Alkem and
MSD. No data on suppliers’ sites is available for five companies: Alkem, Fresenius
Kabi, Hainan Hailing, MSD and Sun
Pharma.

200

400

600

870
800

1000

Manufacturing sites

43Responsible manufacturing – context

Antimicrobial Resistance Benchmark 2021

T WO T YPI CAL WAYS ANTI BACTE RIAL WASTEWATE R IS D ISCHARG E D I NTO TH E E NVI RO N M E NT
Antibacterial manufacturing sites produce wastewater which contains active pharmaceutical ingredients (APIs). These diagrams demonstrate two of the mostcommon ways in which those wastewaters are discharged into the environment, for example into a river near the manufacturing site.

OPTION 1. Wastewater is directly discharged into the environment

OPTION 2. Wastewater is sent to a public wastewater treatment plant,
before being discharged into the environment

factoryfactory

contains highconcentrationsof API

on-sitetreatment

on-sitetreatment

contains highconcentrationsof API

otherwastewater3

wastewatercontains APIs
and resistantbacteria

river

companies
apply limits inriver water
2

1

publicwastewater
treatment plant

wastewatercontains APIs
and resistantbacteria

companies
apply limits inriver water

2
river

1

bacteria

1

APIs

resistant bacteria

While solid waste containing antibacterials is typically sent for incineration, liquid
waste is discharged into the environment. As recommended by the AMR Industry
Alliance, companies generally assess whether they have met limits by calculating
concentrations in the receiving environment (e.g. the river) rather than directly inthe wastewater leaving the manufacturing site after on-site treatment. As such, thewastewater will often be strongly diluted at the point where limits are applied.
Applying limits directly to the wastewater before it is discharged into the environment would be a more desirable approach in the fight against rising AMR. This isbecause selection of antibiotic-resistant bacteria can still occur in the wastewater
itself, due to the presence of bacteria and high concentrations of antibacterials.5,7–12
In addition, if wastewater containing high levels of APIs is sent to public wastewater
treatment plants, it also poses a risk as these plants are known hotspots of selection for resistance.13,14

2

When companies treat wastewater on-site, especially using biological methods, many bacteria will still be present in the wastewater, leading to the risk ofresistance.

3

It is important to note that public wastewater treatment plants also receive otherwastewater from municipalities, which can contain high levels of bacteria but also
antibacterial residue as result of human use.15

44

Antimicrobial Resistance Benchmark 2021

RESPO NSI B LE MAN U FACTU RI NG – SU PPLY CHAI N STR ATEG I ES

Self-regulation is the basis for companies’
environmental risk-management strategies
What does the Benchmark assess?

KE Y TE R M S

The Benchmark looks at whether companies’ environmental risk-management

Environmental risk-management strategy

strategies include:• Management systems and treatment practices, including details of techniques
and processes to collect and treat both solid waste and wastewater;• Details on plans for periodic audits for sites, including how to identify problematic
processes and to initiate corrective and preventive action (CAPA, see right);• Defined limits, set specifically for the maximum levels of antibacterial residue present in waste/wastewaters, such as predicted no-effect concentrations(PNECs, see right);• Details on plans for risk assessments and monitoring of discharge levels at allsites, so that compliance with set limits can be assessed.
It is critical that pharmaceutical companies implement strategies at their own
sites, as well as requiring their suppliers and waste-treatment contractors to meetthe same environmental standards.​

A strategy developed specifically to minimise
the impact of manufacturing processes used at
a manufacturing site on the environment, and toaddress the associated risk of AMR.
Corrective and preventive action (CAPA)
A set of actions or improvements which can be
implemented by a company in order to tackle
non-compliance, and to make sure these issues
do not occur in future.
Predicted no-effect concentration (PNEC)
The highest estimated concentration at which
no adverse effects on the environment, such as
the opportunity for resistance selection or harm
to aquatic life, are expected to occur.16,17,18

How wastewater limits and targets have been establishedOf the 801 antibacterial products in scope, 688 (86%) have an established science-based PNEC target laid out in the recommended list by the AMR Industry
Alliance. In February 2021, a default value was added to the list for those active
ingredients which do not have a specified target as of yet.19
Twelve of the 17 companies apply the PNECs as voluntary targets. However,there are currently no legally binding limits for antibacterial discharge from man-

The role of the AMR Industry Allianceufacturing. This means there are no legal consequences for companies when tar-

The AMR Industry Alliance is a coalition

gets are not achieved. Responsibility lies with governments to develop a regulatoryof pharmaceutical companies formed

framework with limits for emissions of antibacterial waste, in order to incentivise

in 2016 to deliver on the commitments

action when safe levels are not met.

made in the Davos Declaration on curbing AMR.

How levels of antibacterials are quantified by companies

Twelve of the 17 companies in scope

Rather than measuring antibacterials in wastewater samples, it is common practicehave made a public commitment tofor companies to calculate the final concentrations in the receiving environment.

assess their own and suppliers’ sites

This is also known as the mass balance approach and consists of:through the AMR Industry Alliance’s• Estimating how much of the antibacterial ingredient is lost in the production pro-Common Antibiotic Manufacturing

cess and will end up in waste, i.e. the mass balance;

Framework (CAMF). These companies• Estimating how much antibacterial residue is removed by on-site treatment (andinclude all the large research-based com-other treatment plants if applicable);

panies in scope, as well as the generic• Applying dilution factors due to water flows from treatment plants and rivers, if

medicine manufacturers Aurobindo,

applicable.

Fresenius Kabi, Teva and Viatris. CAMF

Nine of the 17 companies report that, only when deemed necessary, mass balanceis a publicly available tool that provides

calculations are verified by sampling wastewater and performing chemical analy-

strategic recommendations on handlingsis. This verification is helpful to make sure the approach used for calculations isand treatment of antibacterial waste,accurate, or to check whether calculations are correct and whether limits have truly

risk assessment, and auditing to mini-

been met or exceeded.

mise AMR risk from antibacterial manufacturing. 21
As implementation is an ongoing process, long-term action plans need to
be developed and tailored by eachcompany.

45

Responsible manufacturing – supply chain strategies

Antimicrobial Resistance Benchmark 2021

TABLE 6. Depth and breadth of environmental risk management strategies
As in 2020, the 2021 Benchmark looks at whether companies’ environmental risk-management
strategies include audits, limits and quantification of antibacterial discharge (depth), as well as
examining where and how companies apply these strategies (breadth).
Third-party suppliers of APIs
Own manufacturing sites

and/or drug products

External private waste-treatment plants

Strategy & audits

Limits &quantification

Strategy & audits

Limits &quantification● Strategy to limit
AMR adopted, including audits and CAPA

● All sites have quantified discharge levels
against set limits● Strategy adopted
by suppliers, including
audits and CAPA

● Suppliers asked to
set limits and reportdischarge levels● Company has set
limits but not all sites
have quantified discharge levels● Strategy not fully● Suppliers asked toadopted by suppliers
set limits; unclear how
and supplier audits not levels are assessed
performed yet

Strategy & Audits● AMR-specific auditsof private plants*● General audits ofprivate plants only

Limits &quantification● Private and/or
public wastewater
plants asked to set
limits and report discharge levels○ No or limited evidence that the company fulfills the corresponding element

Large research-based pharmaceutical companies
GSK

●

●

●

●

●

○

Johnson & Johnson

●

●

●

●

●

○

MSD

●

●

●

●

●

○

Novartis

●

●

●

●

●

○

Otsuka

○

○

○

○

○

N/A

Pfizer

●

●

●

●

●

○

Sanofi

●

●

●

●

●

○

Shionogi

●

●

●

●

●

N/A

Abbott

●

●

●

●

●

○

Alkem

○

○

○

○

○

○

Aurobindo

●

●

●

**

●

○

Cipla

●

●

●

●

○

○

Fresenius Kabi

●

○

○

○

○

○

Hainan Hailing

○

○

○

○

○

○

Sun Pharma

○

**

○

○

○

○

Teva

●

●

●

○

○

○

Viatris

●

●

●

●

○

○

Generic medicine manufacturers

SANOFIVIATRISSHIONOGI

Sanofi implemented a Health Safety andZero liquid discharge (ZLD) technology

Shionogi’s sole directly-operated man-

Environment management system (HSE)

is a treatment process in which the site

ufacturing site is located in Kanegasaki,

and Pharmaceuticals In the Environment

does not discharge any water into theJapan, and this is where it manufac-(PIE) programme. These include envi-

environment as this will be reused andtures five out of its eight antibacterialronmental requirements intended torecycled, while solid residue is inciner-

products. The three remaining medi-

minimise the impact of the discharge of

ated or sent to landfill after treatment.21

cines are produced by third-party sup-antibacterials on the environment.

Of the five companies which currently

pliers. For Shionogi’s products, five of its

implement ZLD, Viatris is the only com-

APIs have an established science-basedpany to report that it has taken the extra

PNEC. For those APIs without a specificstep of analysing the recycled water to

PNEC, Shionogi applies a default value

check for the presence of APIs, whichof 0.01 μg/L. Shionogi has set the expec-

was found to be at zero.

tation that its suppliers must also follow
these limits.

* The Benchmark looks whether audits
assess if waste treatment plants have inplace: 1) suitable technologies to treat,
store and dispose antibacterial waste, asapplicable; 2) protocols to prevent con-tamination of antibacterial waste in soil,
surface and groundwater, as applicable.

** Company indicates all applicable sites
are ZLD. It is unclear how the company assures these sites are not a risk
for AMR – for example, whether recycled water is analysed for the presence ofantibacterials.

N/A indicates the company does not makeuse of any private or public wastewater
treatment plants.

46

Antimicrobial Resistance Benchmark 2021

RESPO NSI B LE MAN U FACTU RI NG - SU PPLY CHAI N STR ATEG I ES

Companies increasingly require their
suppliers to set discharge limits
Antibiotic manufacturing chains are sprawling and complex, with many

FIGURE 32. Uptick in companies requiring all suppliers todifferent suppliers delivering active pharmaceutical ingredients (APIs)

set discharge limits

and drug products to downstream partners. Pharmaceutical companies,

Since the first Benchmark was published in 2018,** there has

including both large-research based companies and generic medicine

been an increase in the number of companies requiring

manufacturers, occupy dominant positions in these supply chains as the

suppliers to set limits on antibiotic wastewater discharge into

suppliers’ major customers, and are therefore uniquely placed to influ-

the environment.

ence the standards and practices of those upstream suppliers.

Three generic medicine manufacturers
require suppliers to set
limits, namely Abbott,
Cipla and Viatris.

The Benchmark firstly examines whether pharmaceutical companies
implement ambitious AMR risk-management strategies and standards attheir own sites, and then examines whether they require their suppliers

11

and waste treatment plants to also meet the same standards.
Limits are set out in companies’ environmental risk-management

7

10

strategies, and indicate the highest acceptable level of antibacterial resi-

3

due which should be present in antibacterial manufacturing waste whenreleased into the environment.*7

6
3

Progress in requiring suppliers to set limits

2018 2020 2021

Companies generally perform the best at setting and monitoring specific

Generic medicine
manufacturers which require
suppliers to set limits
Large research-based
pharma companies which
require suppliers to set
limits

AMR-related standards at their own manufacturing sites, as can be seen

All large researchbased companies
in the Benchmark’s
scope now require
suppliers to set discharge limits, except
for Otsuka.

in Table 6. However, there is progress in requiring suppliers’ manufacturing sites to also meet specific standards around limits on the levels ofantibacterial residue in wastewater.
All assessed large research-based companies now report that theyrequire suppliers to set discharge limits, except for Otsuka. Since the2020 Benchmark, Sanofi newly reports requiring its suppliers to set
limits.

FIGURE 33. How far do discharge limits apply along the

In the previous two iterations of the Benchmark, no generic medicine

supply chain?

manufacturers reported that they required suppliers to set limits. Now,

This chart shows how many of the companies apply discharge

for the first time, the Benchmark can report that three generic medi-

limits along the supply chain.

cine manufacturers require suppliers to set limits, namely Abbott, Cipla
and Viatris. Abbott, for example, introduced a new contract template for7

suppliers in 2021, with clauses that specifically require implementationof AMR standards. If corresponding audit results are not satisfactory,
Abbott can enforce contractual provisions.

Generic medicine
manufacturers

Looking at the other generic medicine manufacturers, Teva has
future plans in place to assess suppliers and require them to set limits.
Fresenius Kabi encourages suppliers to set limits – but formal mechanisms such as audit requirements or specific terms in supplier contracts,
are not in place.

Large R&D-based
companies
supply chain

5

17

5
3
7

At
suppliers'
sites

7
0
At
own sites

At wastetreatment
plants

No company requires external waste-treatment
plants to set limits. Companies could engage
with all external waste-treatment plants to raiseawareness and require them to manage AMR-related risks from wastewater discharge to theenvironment.

* When companies report sites as compliant with limits, it means the estimatedconcentration in the receiving environment is safe, not in the wastewater leaving the manufacturing site itself.

** In 2018, the following companies were
not in scope: Abbott, Alkem, Hainan
Hailing and Otsuka. They have been in
scope since the 2020 Benchmark.

47

Antimicrobial Resistance Benchmark 2021

RESPO NSI B LE MAN U FACTU RI NG – CO M PLIANCE WITH LI M ITS

Reported compliance with limits lags
behind, especially at suppliers’ sites
As the number of sites that set limits to mitigate the risk of AMR increases, the next

The challenge of compliancestep is to examine whether these limits are achieved in practice. The Benchmark

Companies can have over 20 manufacturing

surveyed the 17 companies in its scope to assess levels of compliance with limits,
looking across companies’ own sites and those of their suppliers.

sites and 200 suppliers’ sites, making it a complex and time-consuming challenge to assess
standards at all sites. Reaching compliance is aMore sites regularly monitored for compliance, but a long way still to go
There are 1,057 sites in scope, consisting of 187 of the companies’ own sites (basedon data from 15 companies) and 807 supplier sites (based on data from 12 companies).* The majority of sites are reported to be subject to discharge limits. However,less than a third of all sites are reported as quantifying discharge levels to determine compliance with limits, while 13% are reported as compliant with the limits set.
Focusing in on suppliers’ sites, the ‘compliance gap’ or ‘data gap’ becomes clear.
Whereas 97 out of the pharma companies’ 187 directly-operated sites included inthis analysis are reported as compliant (52%), just 45 of the 870 suppliers’ sites arereported as compliant (5.2%).

work in progress, which makes it key for companies to have environmental standards rooted
in their long-term strategies, and to assign sufficient resources.
Data and transparency
This Benchmark captures data companies’ practices at manufacturing sites along their supply
chains. In future assessments, it will be important to take a step further and require companies to report on actual volumes of antibacterials that are manufactured per site to better map
the risk of selection for resistance associatedwith manufacturing.

FIGURE 34. Even where limits are set, quantification and compliance lags behindCompanies’ own manufacturing sites
This figure shows how many of the pharma companies’ 187 directly-operated manufacturing sites
report setting or requiring limits, quantifying discharge levels and being compliant with set limits.
Reported sites
without limits,
or no data available

Reported sitesthat are required
to set limits

Sites reported
as compliant
with limits

Reported sitesthat quantify

24

24
22

187
sites

163
sites withlimits

163

22

141

Reported sites that
do not quantify,
or no data available

41

142

141
sites thatquantify

Discharge limits are set at 163 of the companies’
own manufacturing sites – and of those sites,
more than three quarters are reported as quantifying discharge levels. More than half are reported
as compliant with discharge limits.

127
97
45

3

Sites where results
are not reported

Sites reported as
not compliant

Suppliers’ manufacturing sites
This figure shows how many sites, out of the total of 870 suppliers’ sites, report setting or requiring
limits, quantifying discharge levels and being compliant with set limits.
Reported sites thatare required to set
limitsReported sites thatquantify

Sites reported as compliant
with limits
45

173
309

870
sites
561

561
sites withlimits173
sites thatquantify

388
Reported sites
without limits,
or no data available* No data on any manufacturing sites isavailable for two companies: Alkem and
MSD. No data on suppliers’ sites is available for five companies: Fresenius Kabi,
Hainan Hailing and Sun Pharma.

Reported sites that
do not quantify,
or no data available

124

Sites where results
are not reported
4
Sites reported as
not compliant

While 561 supplier sites are required to set discharge limits, quantification of discharge levels is
only reported at 173 sites. That leaves 388 sites
where, although limits have been set, no actions
are reported as being taken to check whether theactual levels of antibacterial residue in wastewaters are compliant with these levels. Only 45 sites
are reported as compliant with limits.
While four sites are reported as not compliant,compliance data is not available – or has not been
made available – for the majority of suppliers’sites. It is crucial that pharma companies collectand report on compliance data across their entire
supply chains.

48

Antimicrobial Resistance Benchmark 2021

Responsible manufacturing – compliance with limits

FIGURE 35. Most sites are operated by third-party suppliers, and compliance rates here are low

Despite many companies reportingthat they require their suppliers to
set limits, almost none of the suppliers are reported to be compliant
with discharge limits as of yet.

This figure shows how many sites (left) and what percentage of sites (right) are compliant with
discharge limits, broken down by whether they are operated by large-research-based companies,
generic medicine manufacturers, or third-party suppliers of both.
Sites operated by:Sites operated by:Large research-based companies

63 30

Large research-based companies

Generic medicine manufacturers

34 60

Generic medicine manufacturers

Third-party suppliers

45
0
200

400

600

825
800

Reported as compliant with limits

67.7%
36.2%

Third-party suppliers

63.8%

5.2%

1000
Sites

0%

50%

Reported as compliant with limits

Reported as not compliant, or no data available

32.3%
94.8%
100%
Sites

Reported as not compliant, or no data available

TABLE 7. Supplier data often not available, but more positive signs at companies’ own sites

BEST PRACTICE

This table shows the percentage of each company's manufacturing sites, broken down by own and

GSK

suppliers’ sites, which are reported as compliant with discharge limits. Some company names are

GSK reports that all 20 of its own sites

covered by NDAs. Many companies do not assess or report whether manufacturing sites are compliant

and 37 out of 39 of its suppliers’ sites

with discharge limits.

are compliant with discharge limits set in

Reported as compliant with limits- Reported as not compliant, or no data
available

Aurobindo reports that all of its 15 sites are compliant with discharge limits, making up almost halfof the total number of generic medicine manufacturers’ sites which are reported as compliant.

Of the 45 supplier sites reported ascompliant, almost all of them werereported as such by GSK.

the receiving environment. For its own
manufacturing sites, GSK states that themost important steps to achieve compliance involve:

Level of compliancewith discharge limits

At own sites

At suppliers' sites

High: 70-100%

Number of companies: 5• Aurobindo• GSK• Shionogi• Viatris• 1 large research-based
company

Number of companies: 1• GSK

Number of companies: 3• 2 large research-based
companies• 1 generic medicine
manufacturer

Number of companies: 0

Number of companies: 2• Cipla• TevaNumber of companies: 2• Shionogi• 1 large research-based
company

Number of companies: 7• 3 large research-based
companies• 4 generic medicine
manufacturers

Number of companies: 14• 5 large research-based
companies• 9 generic medicine
manufacturers

Medium: 40-70%

Low: 1-40%

No data

1. Optimising source control and cleaning procedures to reduce losses inwastewater. This includes vacuum
cleaning and pre-rinsing of manufacturing equipment. Concentrated
streams are collected at the point ofgeneration and sent for proper disposal, such as incineration.
2. Installing pre-treatment technology such as pH or thermal hydrolysis,thin-film evaporation dryers, electrochemical oxidation, and multi-effectevaporation.
GSK reports that contracts with suppliers are discontinued when suppliers are
not compliant with discharge limits. To
assist suppliers towards reaching compliance, GSK promotes the use of tools

FIGURE 36. Companies ensuring quality management systems across their supply chainsand guidelines that help to assess andCompanies are expected to produce their antibacterials using the highest standards to ensure quality

reduce their antibacterial discharges.

and minimise the risk that patients are exposed to sub-therapeutic levels, which drive AMR.22

Furthermore, GSK provides detailed

While all companies have quality management systems (QMS) in place, several companies are also

guidance to suppliers based on experi-

pushing up standards upstream.

ences from the company’s own manu-

17

7

15

9

All 17 companies
have a QMS at theirown manufacturing
sites

15 companies gofurther by auditing
their suppliers’
QMS* Otsuka reports that its suppliers do nothave any suppliers of their own.
** The period of analysis is 22 June 2019 30 April 2021, inclusive.

During the period of analysis,**antibacterial sites operated
by Aurobindo and a subsidiaryof Teva have received a GMP
non-compliance inspection
result of ‘Official Action Indicated’ (OAI) from the FDA. Dueto the COVID-19 pandemic,
re-inspections by the FDA are
delayed.

facturing sites.

9 companies go thefurthest by also requiringthat suppliers audit theirown suppliers’ QMS*

49

Antimicrobial Resistance Benchmark 2021

RESPO NSI B LE MAN U FACTU RI NG – TR ANSPARE NCY

Transparency from companies inches
forward
Data on compliance with environmental standards at manufacturing sites can often

The benefits of transparancy

only be reported by the Benchmark in an aggregate manner due to requests for

Without this information, it is difficult for inde-confidentiality. Very few companies publicly report any level of detail on either thenumber of manufacturing sites audited, or on how many of these sites report compliance with safe levels. No company publicly reports on the actual levels of antibacterial residue entering local soil and water, and no company publishes its audit

pendent third parties, including academic
experts and government institutions, to critically assess if there is any progress and impact
in making sure that antibacterial discharge levels
are safe. A lack of transparency also hinders
evaluation of the accuracy of mass balance esti-

results.
The AMR Industry Alliance has a central role in setting strategy and deciding on
public disclosure across the industry. But of the 12 members in scope, two companies (Fresenius Kabi and Otsuka) have not yet set limits at their own sites, andfive companies (Aurobindo, Fresenius Kabi, Otsuka and Teva) have not yet formallyrequired their suppliers to set limits. Cipla and Abbott report following the AMR
Industry Alliance’s guidelines, despite not being a member.
Two companies, GSK and Shionogi, stand out by reporting on whether the levels of antibacterial discharge found at their manufacturing sites (both directly-operated and suppliers’ sites) comply with the limits set. This information is available

mations compared to sampling, and what dilution factors are applied.
The publication of both a) the methods used by
the companies, and b) the resulting data, would
permit deeper understanding of the current situation, opportunities for optimisation, and thedissemination of good practice. It would allow
procurers to examine AMR-associated risks of acompany’s manufacturing practices in their procurement processes.23

in their annual or environmental reports. Novartis also reports on whether its own
sites are compliant with pharmaceutical limits, though the company’s data is not
specific to sites producing antibacterials.
Of the 12 companies that report setting limits, nine also publish their commitment to these limits via their websites or annual reports. The three that do not are
Abbott, Aurobindo and Cipla. Publicly committing to set limits is important so companies can be held accountable when not living up to their own words.

FIGURE 37. Number of companies which report setting limits at their

SHIONOGI

own directly-operated manufacturing sites

Environmental report 2020

This figure shows how many of the 17 companies in scope publicly commit

Shionogi leads the way when it comesto setting limits and publishing compliance with limits for their own sites.

to public disclosure, by publishing many

More companies now make this commitment compared to the 2020

aspects of its environmental risk-man-

Benchmark.

agement strategy in its environmental
14report. The company shares which anti-

8bacterials it has in its portfolio, and maps
the manufacturing of these products to2
7
32020 2021

Commits publicly to setting
limits; reports compliancethe company’s own sites and suppliers’sites, reporting which are compliant with
discharge limits. Furthermore, the loca-

Commits publicly tosetting limits

tion of suppliers and the name of its only
external waste-treatment plant are also
disclosed. Altogether, Shionogi serves
as a positive example of a company thatprovides clarity about its antibacterial
manufacturing supply chain.

50

Antimicrobial Resistance Benchmark 2021

RESPO NSI B LE MAN U FACTU RI NG – ANTI FU NGALS

Companies do not prioritise antifungals inenvironmental risk management
As in 2018 and 2020, this Research Area focuses on antibacterials. However, antifungals are an area of emerging concern due to the high rate of cross-resistance
between compounds employed as both broad-spectrum human antifungals andfungicides in agriculture.24 The WHO is concerned about the public health threatof fungal infections, together with the rise in antifungal resistance, and is therefore developing a global fungal priority pathogens list to make sure R&D efforts are
effectively prioritised.25
The list published by the AMR Industry Alliance includes targets for discharge
limits for antifungals. However, in recent years, targets for 21 antifungal products inscope, marketed by 11 companies, have been removed from their list.19 As a result,only 13 out of all 120 (11%) antifungal products in scope have a defined PNEC value
which sets out what concentration would be considered safe. While the Alliance issteering away from antifungals, it is important that companies ensure limits apply
to all antifungal products they manufacture and bring to market. The scientific fieldalso has a role to play in defining science-based targets for more antifungals.

FIGURE 38. How do the companies’ approaches to environmental risk management differ
between antibacterial and antifungal products?
Antibacterials
Set limits

Market antibacterials

5

Quantify levels
All 17 companies in scope are marketing antibacterial products. The majority of companies reportthat they set limits, and that they quantify levels
to check whether limits have been met.

5

17companies

17
companies

12companies
12

12

17
Do not set limits
Antifungals
Set limits

Market antifungals

2

2

2

17
companies

15
companies

7

Quantify levels

8

7

15

5

7
companies

Eight companies report an environmental strategy that covers antifungal manufacturing compared to seven in 2020, showing little progress.

3

3
Do not set limits

Fifteen of the 17 companies in scope are marketing antifungal medicines. Just over half reportthat they set limits, and only a third report thatthey quantify discharge levels to assess whether
limits are met.

Do not quantify
levels51

Antimicrobial Resistance Benchmark 2021

RESPO NSI B LE MAN U FACTU RI NG

Looking ahead

There are many actions which companies, governments, scientists, procurers andinvestors can take to break the link between antibacterial manufacturing and antimicrobial resistance, by ensuring that unsafe quantities of antibacterials are not discharged into the environment. This page sets out the positive actions each group of
stakeholders can take.

CO M PAN I ESG OVE R N M E NTS AN D PRO CU R E RS

Increase transparency, e.g. via the AMR Industry Alliance,• Develop regulatory frameworks, as current environmental

about the actual levels of antibacterial residue entering theregulations do not include limits on the levels of antibacte-environment. This would allow other stakeholders such as

rials allowed in wastewaters from manufacturing.

academics, procurers and government institutions to study• Include environmental regulations and transparency stipula-

the relationship between wastewater management and AMR,

tions in procurement contracts for products subsidised with

as well as independently assess companies’ performance andprogress.

public funding, in order to promote responsible behaviour.
• Require public disclosure from companies, not just on discharge levels but also on their supply chains. For exam-

At companies’ own sites

ple, the New Zealand Medicines and Medical Devices Safety• Follow through on progress in setting limits by ensuring full

Authority collates and publishes information from compa-

compliance with those limits.
• Apply limits directly to wastewater, instead of applying limits in receiving environments such as rivers.

nies on the full supply chain of each marketed product in a
publicly available database.26 Such information includes: 1)
where and by who the products are manufactured, packaged, and released; 2) which suppliers (including names

At suppliers’ sites• Ensure all sites monitor discharge levels to assess compliance with limits, and report on the results.
• Share knowledge and experience from directly-managed

and locations) supply each active ingredient; 3) the productsponsors.
• Spur public-private collaborations with a focus on removing
antibacterials from industrial wastewater. For example, thesites, in order to help suppliers manage their own wastewa-

Responsible Antibiotics Manufacturing Platform (RAMP)

ter disposal.

works with multiple stakeholders towards more sustainably-produced antibiotics and transparency.27 Another inter-At waste treatment plants

national collaboration aims to develop a system for char-• Extend environmental risk management strategies toacterising the environmental risks of existing APIs. Such a

waste treatment plants, to assure responsible process-system could also be used by companies to identify envi-

ing of industrial waste streams with high concentrations ofronmental concerns related to AMR earlier in the drug

antibacterials.

development process.28 Finally, a Dutch consortium aims to• Share data on water flows, for accurate quantification ofdischarge levels.

develop technological solutions and innovation capacity to
reduce antibacterial waste streams.29• Use sustainability-focused policies to stimulate companies

SCI E NTI FI C FI E LD

to meet environmental criteria. Companies are then incen-• Expand the evidence base and refine the definition of safe

tivised to gain a competitive advantage to secure tenders

limits for a wider range of antibacterials and antifungals.

or sales contracts, as applicable.31,32 This approach has been

• Further increase the broader understanding of the role ofpiloted in Sweden and Norway.32,33

environmental bacteria, wastewaters and selection pressures in the development of AMR.

I NVESTO RS• When making investment decisions, consider whether
companies manufacture in a way that is environmentally
responsible and mitigates the risk of AMR.
• Encourage companies to participate in sustainability-focused initiatives and pilot programmes.

52

Antimicrobial Resistance Benchmark 2021

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Supply Chain.; 2016.
2. Karkman A, Pärnänen K, Larsson DGJ.
Fecal pollution can explain antibiotic
resistance gene abundances in anthropogenically impacted environments.
Nat Commun. 2019;10(1). doi:10.1038/
s41467-018-07992-3
3. Kristiansson E, Fick J, Janzon A, et al.
Pyrosequencing of antibiotic-contaminated river sediments reveals high levelsof resistance and gene transfer elements.
PLoS One. 2011;6(2). doi:10.1371/journal.
pone.0017038
4. Li D, Yang M, Hu J, Ren L, Zhang Y, Li
K. Determination and fate of oxytetracycline and related compounds in oxytetracycline production wastewater andthe receiving river. Environ Toxicol Chem.
2008;27(1):80-86. doi:10.1897/07-080.1
5. Larsson DGJ. Pollution from drug
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rstb.2013.0571
6. Bielen A, Šimatović A, Kosić-Vukšić J,
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Res. 2017;126:79-87. doi:10.1016/j.
watres.2017.09.019
7. Marathe NP, Shetty SA, Shouche
YS, Larsson DGJ. Limited Bacterial
Diversity within a Treatment Plant
Receiving Antibiotic-Containing Waste
from Bulk Drug Production. PLoS
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JOURNAL.PONE.0165914
8. Marathe NP, Regina VR, Walujkar
SA, et al. A Treatment Plant Receiving
Waste Water from Multiple Bulk Drug
Manufacturers Is a Reservoir for Highly
Multi-Drug Resistant Integron-Bearing
Bacteria. PLoS One. 2013;8(10):e77310.
doi:10.1371/JOURNAL.PONE.0077310
9. Kraupner N, Hutinel M, Schumacher K,
et al. Evidence for selection of multi-resistant E. coli by hospital effluent. Environ
Int. 2021;150:106436. doi:10.1016/J.
ENVINT.2021.106436
10. Johnning A, Moore ERB, SvenssonStadler L, Shouche YS, Joakim Larsson
DG, Kristiansson E. Acquired genetic
mechanisms of a multiresistant bacterium
isolated from a treatment plant receiving
wastewater from antibiotic production.
Appl Environ Microbiol. 2013;79(23):72567263. doi:10.1128/AEM.02141-13
11. Milaković M, Križanović S, Petrić I, etal. Characterization of macrolide resistance in bacteria isolated from macrolide-polluted and unpolluted river sediments and clinical sources in Croatia. Sci
Total Environ. 2020;749. doi:10.1016/j.
scitotenv.2020.142357
12. Larsson DGJ, Flach C-F. Antibiotic
resistance in the environment. Nat

Rev Microbiol 2021. Published online
November 4, 2021:1-13. doi:10.1038/
s41579-021-00649-x

Clinical Use of Mold-Active Antifungal
Azoles? Clin Infect Dis. 2016;62(3):362368. doi:10.1093/cid/civ885

13. Zieliński W, Korzeniewska E, Harnisz
M, Drzymała J, Felis E, Bajkacz S.
Wastewater treatment plants as a reservoir of integrase and antibiotic resistance genes – An epidemiological threat
to workers and environment. Environ
Int. 2021;156:106641. doi:10.1016/J.
ENVINT.2021.106641

25. WHO Report. First meeting of the
WHO antifungal expert group on identifying priority fungal pathogens. World
Health Organization (WHO). Published2020. Accessed September 5, 2021.
https://www.who.int/publications/i/
item/9789240006355

14. Osińska A, Korzeniewska E, Harnisz M,
et al. Small-scale wastewater treatment
plants as a source of the dissemination of
antibiotic resistance genes in the aquatic
environment. J Hazard Mater. 2020;381.
doi:10.1016/j.jhazmat.2019.121221
15. Karkman A, Do TT, Walsh F, Virta MPJ.
Antibiotic-Resistance Genes in Waste
Water. Trends Microbiol. 2018;26(3):220228. doi:10.1016/J.TIM.2017.09.005
16. Bengtsson-Palme J, Larsson DGJ.
Concentrations of antibiotics predicted to
select for resistant bacteria: Proposed limits for environmental regulation. Environ
Int. 2016;86:140-149. doi:10.1016/J.
ENVINT.2015.10.015
17. Tell J, Caldwell DJ, Häner A, et al.
Science-based Targets for Antibiotics in
Receiving Waters from Pharmaceutical
Manufacturing Operations. Integr Environ
Assess Manag. 2019;15(3):312-319.
doi:10.1002/ieam.4141
18. Le Page G, Gunnarsson L, Snape J,
Tyler CR. Integrating human and environmental health in antibiotic risk assessment: A critical analysis of protection
goals, species sensitivity and antimicrobial
resistance. Environ Int. 2017;109:155-169.
doi:10.1016/j.envint.2017.09.013
19. AMR Industry Alliance. AMR Alliance
Science-Based PNEC Targets for Risk
Assessments. 2021;February:5.
20. AMR Industry Alliance. COMMON
ANTIBIOTIC MANUFACTURING
FRAMEWORK.; 2018. doi:10.1002/
etc.3163/pdf
21. Ranade V V., Bhandari VM. Industrial
Wastewater Treatment, Recycling andReuse. Ind Wastewater Treat Recycl
Reuse. Published online July 21, 2014:1560. doi:10.1016/C2012-0-06975-X

26. MEDSAFE: New Zealand Medicines
and Medical Devices Safety Authority.
Accessed October 20, 2021. https://www.
medsafe.govt.nz/regulatory/DbSearch.asp
27. Responsible antibiotics manufacturing platform (RAMP) - SIWI. Accessed
October 27, 2021. https://siwi.org/
amr-ramp/?accordion-our-impact
28. IMI-PREMIER– Prioritisation andRisk Evaluation of Medicines in the
EnviRonment. Accessed October 20,
2021. https://imi-premier.eu/
29. Dutch Consortium Antibiotics
and, Pharmaceutical Residues from
Water. Removal of Antibiotics andPharmaceutical Residues in Water
Urgent.; 2021.
30. Årdal C, Baraldi E, Beyer P, et al.
Supply chain transparency and the availability of essential medicines. Bull
World Health Organ. 2021;99(4):319.
doi:10.2471/BLT.20.267724
31. SIWI. Reducing Emissions from
Antibiotic Production . Published online
2020. Accessed October 20, 2021. www.
siwi.org/publications
32. Regeringskansliet. Försöksverksamhet
för miljöpremie i läkemedelsförmånssystemet. Published 2021. Accessed October27, 2021. https://www.regeringen.se/pressmeddelanden/2021/05/forsoksverksamhet-for-miljopremie-i-lakemedelsformanssystemet/
33. New environmental criteria forthe procurement of pharmaceuticals Sykehusinnkjøp. Accessed November 8,2021. https://sykehusinnkjop.no/nyheter/
new-environmental-criteria-for-the-procurement-of-pharmaceuticals

22. Weinstein ZB, Zaman MH. Evolutionof Rifampin Resistance in Escherichia coli
and Mycobacterium smegmatis Due to
Substandard Drugs. Antimicrob Agents
Chemother. 2018;63(1). doi:10.1128/
AAC.01243-18
23. Larsson DGJ, Fick J. Transparency
throughout the production chain—a
way to reduce pollution from the manufacturing of pharmaceuticals? Regul
Toxicol Pharmacol. 2009;53(3):161-163.
doi:10.1016/j.yrtph.2009.01.008
24. Verweij PE, Chowdhary A, Melchers
WJG, Meis JF. Azole Resistance inAspergillus fumigatus: Can We Retain the53

Antimicrobial Resistance Benchmark 2021

54

Antimicrobial Resistance Benchmark 2021

CO NTEX T

Appropriate Access

The antibiotics and antifungals available today make it possible
to prevent and control the spread of infection in communities andhospitals. They cut the risk of infection after surgery, and protect
people undergoing aggressive treatments, such as for cancer. Yeteight times as many people currently die from lack of access to
medicine as from drug-resistant infections.1 Action to improve theavailability and accessibility of medicines and vaccines is urgently
needed, with each antibiotic and antifungal being used responsibly to ensure it stays effective for as long as possible.
More people die from treatable infectious diseases than from drug resistanceAn estimated 700,000 people die each year due to drug-resistant infections. By
comparison, 5.7 million people die from treatable infectious diseases.1 Most ofthese people live in low- and middle-income countries (LMICs).
Lack of access to medicine can drive up drug resistance
Shortages, stockouts and unavailability of medications can lead to patients being
given ineffective or inappropriate drugs for their illnesses, contributing to AMR andgiving pathogens extra opportunities to develop resistance.2
Pharma companies can improve access in LMICs
The range of actions which pharma companies can take includes registering
medicines and vaccines for sale in a country, taking steps to address affordability
and availability, building up the technical skills and knowledge needed for local
manufacturing, and strengthening supply chains to prevent shortages.

H OW PHAR MA CO M PAN I ES C AN D I R EC TLY AD D R ESS ACCESS

Registration

Ensuring affordability

Capacity building

Preventing shortages

Filing a product with national

Globally, medicine is theCompanies can contribute to

A continuous supply of good

regulatory authorities inlargest household expend-

local manufacturing capac-

quality medicines, usedeach country is a key step

iture after food. In LMICs,

ity by helping LMIC-based

responsibly, saves lives andtowards making it available.

up to 75% of health spend-companies build up their

reduces the risk from resist-

To expand access, companies

ing comes from people’s own

manufacturing knowledgeance. Companies can mit-should submit registration

pockets.1 Companies canand expertise, for example

igate the risk of shortages

dossiers to LMIC authorities

make medicines and vaccines

through technology transfers

in a range of ways, such as

as rapidly as possible after

more affordable throughand voluntary licenses.

maintaining buffer stock,

first market launch.

equitable pricing, voluntarybuilding resilient supply

licensing agreements, andchains, and by predicting andproduct donations.

aligning levels of supply anddemand.​55

Appropriate access – context

Antimicrobial Resistance Benchmark 2021

17 companies in scope for Appropriate AccessCompanies in scope for the 2021 Benchmark

The 2021 AMR Benchmark examines the policies and practices of eight large

Together these companies account for

research-based companies and nine generic medicine manufacturers, looking at

29,031.60 SU* million doses sold annually
Country

their actions to ensure appropriate access to their medicines and vaccines. By volume and value of sales, these companies are among today’s largest players in the
global market for antibacterial and antifungal medicines, and therefore have significant capacity to improve access to their products in the countries with the highest
need.3

FIGURE 39. 166 products in scope for this analysis
Across the 17 companies, the Benchmark identified 166 products, which can be divided
into three categories.

On-patent vaccines
18 on-patent antibacterial
vaccines, marketed by four
companies – GSK, MSD***,
Pfizer, and Sanofi.

18

17

166
products
1311

Large research-based companies

HQ

GlaxoSmithKline plc

GBR

2

Johnson & Johnson

USA

3

Merck & Co, IncUSA

4

Novartis AG

CHE

5

Otsuka Pharmaceutical Co, Ltd

JPN

6

Pfizer Inc

USA

7

Sanofi

FRA

8

Shionogi & Co, Ltd

JPN

Generic medicine manufacturers

On-patent medicines
17 on-patent antibacterial and antifungal medicines, marketed by sevencompanies – Cipla, Johnson & Johnson, MSD,
Otsuka, Pfizer, Shionogi
and Viatris.

Off-patent/generic medicines
131 off-patent/generic medicines marketedby 16 companies – all companies in scope
except for Otsuka.†

1

Abbott Laboratories

USA

2

Alkem Laboratories Ltd

IND

3

Aurobindo Pharma Ltd

IND

4

Cipla Ltd

IND

5Fresenius Kabi AG

DEU

6Hainan Hailing Chemipharma Corp Ltd

CHN

7

Viatris**

GBR

8

Sun Pharmaceutical Industries Ltd

IND

9Teva Pharmaceutical Industries Ltd

ISR

FIGURE 40. 102 countries in scope for access metrics in this analysis
This map shows the 102 low- and middle-income countries in scope of the Benchmark for this Research Area. These
are countries where resistance rates are highest, and where people face the highest burdens of disease.

* Source: IQVIA Midas 2017 anti-infectives
data. Companies with sales volumes
below 1.000 SU million are not included inthis number.

** Mylan has been renamed Viatris, following closing of merger with Upjohn, a division of Pfizer, in 2020.
*** Merck & Co, Inc (Kenilworth, NJ,
United States)† Only the top two off-patent/generic
medicines by global sales volume withineach Appropriate Access category(AWaRe antibiotics, off-patent TB medicines and antifungals) were selected foranalysis.

56

Antimicrobial Resistance Benchmark 2021

APPRO PRIATE ACCESS – REG ISTR ATIO N

Slow progress on registering products inpoorer countries
Filing for registration is a vital first step towards introducing a medical product into

FIGURE 41. The data set for this analysis

a country, as successful registration means that a product is now allowed to be

Products: 166

imported and sold. Companies can register their products with the national regula-Companies: 17

tory authorities of each country, by filing dossiers of technical, medical, and scien-Countries: 102

tific information. Alternatively, in some cases they can make use of special importprocesses that can waive registration for certain essential medicines, such as tuberculosis medicines.

On-patent
vaccines

Typically, pharmaceutical companies first file for registration in higher-income countries with larger markets. However, considering that less wealthy countries often
have the highest need for new products, pharmaceutical companies should register

18 17

On-patent
medicines

166
products

131

their products widely in low- and middle-income countries (LMICs).

Off-patent/generic
medicines

Some signs of progress, much further to go
As in the 2020 AMR Benchmark, in 2021 the products in this analysis are generally
not widely filed for registration across the 102 LMICs in scope.
Only six on-patent medicines have been filed in ten or more of these countries.
Vaccines are filed much more widely than patented medicines, reflecting high international demand as well as the impact of supranational pooled procurement agencies such as Gavi, The Vaccine Alliance.

CHALLE N G ES
Company decision-making

Working with regulators

Lack of transparency

Overcoming access challenges

There are various reasons why a

An increasing number of LMICs

Few online regulatory databases

In response to some of these chal-company may or may not file a

now require marketing authorisa-

yet track the registration of med-lenges, a number of bodies andproduct for registration in a specifiction to license and manufacture

icines in smaller LMICs. Because

programmes have been estab-country, including:a product. Yet, the submission ofregulatory agencies in these coun-

lished, and are already providing• Competing products already on

dossiers can be lengthy and bur-tries may lack the capacity forcompanies with support for prod-

the market in that country;

densome for companies. Some reg-building and updating such data-

uct registration:• Market size and financial

ulatory authorities may also lackbases, companies can play a role in• The WHO Collaborative

opportunities;

the technical expertise to assessbeing more transparent on where

Registration Procedure• Policies on pricing transparency;

the dossier, resulting in long waiting

they file their medicines for reg-

• The African Medicines Regulatory• Political instability, conflict, or

times before regulatory approval.

istration. For example, Johnson

Harmonization (AMRH) programme

economic sanctions;& Johnson is the only company in• The African Medicines Agency• Unclear local regulatory require-

scope to publicly disclose where it(AMA)ments, and long processing times

filed its MDR-TB medicine bedaqui-for registration.

line (Sirturo®) for registration.4

57

Appropriate access – registration

Antimicrobial Resistance Benchmark 2021

FIGURE 42. Which LMICs have the most products being filed?
This map highlights the number of the 166 products in scope which have been filed forregistration in each of the 102 LMICs included in this analysis.

● 0 filings● 1-10 filings● 11-30 filings● 30-50 filings● > 50 filings● not in scope

Which LMICs account for the least registration filings?
There are 14 countries in which none of the products in scope are known
to have been registered. These countries include Somalia and South Sudan,which face political instability, as well as small countries like Tuvalu and Vanuatu, which are hard-to-reach countries that rely on imports for most of their
medicines.

Which LMICs account for the most registration filings?
The five countries within the scope of this analysis where the most registrations have been registered are South Africa, the Philippines, India, Brazil, andThailand. More than 45 filings were reported in those countries during theperiod of analysis, with South Africa benefitting from the highest number offilings (56 in total, across the 166 products).
Compared to other LMICs, these countries provide greater revenue opportunities for pharma companies due to their large patient populations in need,as well as mixed payments from private insurances, public health systems orout-of-pocket expenditure.

58

Appropriate access – registration

Antimicrobial Resistance Benchmark 2021

Many on-patent medicines are not widely filed for registration
On-patent antibiotics and antifungals are typically indicated for very specific cases
or complicated infections, and are targeted at smaller patient populations. Due totheir more restricted use, companies have a lower expectation that they will gain ahigh return on investment, and can find it difficult to estimate the number of people
who could benefit from those medicines in LMICs.
Although volume expectations are lower than for high-volume generic medicines
or vaccines, companies need to continue to register their patented antibiotics andantifungals, especially those which do not benefit from pooled procurement mechanisms, as this is the first step in providing long-term access for patients in low- andmiddle-income countries.
Only three companies – Johnson & Johnson, Pfizer and Viatris – have registered any of their patented medicines in the 34 countries defined as ‘low-income
countries’.
• MDR-TB* medicine bedaquiline (Sirturo®) is approved in seven low-income countries (Democratic Republic of Congo, Burundi, Ethiopia, Rwanda, Tanzania, Uganda
and Zimbabwe).
• Ceftazidime/avibactam (Zavicefta™), used to treat complicated intra-abdominal
infections, complicated urinary tract infections (cUTIs) and hospital-acquired pneumonia, is approved in three low-income countries (Ethiopia, Tanzania, and Uganda).
• M/XDR-TB** medicine pretomanid has been filed for registration in five low-income countries (Democratic Republic of Congo, Ethiopia, Mozambique, Tajikistan
and Zimbabwe).
While Johnson & Johnson and Viatris have filed their TB medicines in countries
with a high TB burden, Pfizer reports that it has filed Zavicefta™ in these countries
based on local patient and provider needs.

FIGURE 43. Which on-patent medicines are filed most widely?
This figure shows in how many of the 102 countries each on-patent medicine is filed for registration.

Bedaquiline(Sirturo®)
Bedaquiline(Sirturo®)
Ceftolozane/tazobactam(Zerbaxa®)
Ceftolozane/tazobactam(Zerbaxa®)

30

Ceftazidime/avibactam(Zavicefta™)
Avibactam/ceftazidime(Zavicefta™)
Ceftaroline(Zinforo®)
Ceftaroline(Zinforo®)

23

Viatris22

Pfizer
Pfizer

20

Pfizer17

Delamanid(Deltyba®)
Delamanid(Deltyba®)
Delamanid(Deltyba™)
Delamanid(Deltyba™)

Otsuka9Viatris7

Plazomicin(Zemdri®)Plazomicin(Zemdri®)Cefiderocol(Fetroja®/Fetcroja®)
Cefiderocol(Fetroja®/Fetcroja®)

Johnson & Johnson
MSD

25

Pretomanid(Dovprela)
Pretomanid(Dovprela)
Anidulafungin(Ecalta;
Eraxis®)Anidulafungin(Ecalta;
Eraxis®)

1

Cipla

0

Shionogi

Tavaborole(Kerydin®)
Tavaborole(Kerydin®)Bezlotoxumab(Zinplava™)
Bezlotoxumab(Zinplava™)0

Pfizerunknown

MSD***

Fidaxomicin(Dificid®)
Fidaxomicin(Dificid®)
Imipenem/cilastatin/relebactam(Recarbrio™)
Imipenem/cilastatin/relebactam(Recarbrio™)

unknown

MSD

unknown

MSD

Posaconazole(Noxafil®)Posaconazole(Noxafil®)Tedizolid(Sivextro®)
Tedizolid(Sivextro®)

unknown

MSD

unknown

MSD

Isavuconazole(Cresemba)
Isavuconazole(Cresemba)

confidential* Multidrug-resistant tuberculosis** Multidrug- and extensively drug-resistant tuberculosis*** MSD declined to provide information
about these products to the Benchmark.
Information about where products are

0

10

20

registered is used by governments, NGOs
and others to inform procurement decisions. Generic medicine manufacturers
also use such information to inform decisions about where to expand their business operations.

Johnson & Johnson’s MDR-TB medicine, bedaquiline, has been filed for registration in 30 of the
LMICs in scope, and is also available via the GDFStop TB Partnership in almost all of the countries in scope. The second most widely-filed medicine is MSD’s ceftolozane/tazobactam (Zerbaxa®), used to treat complicated urinary tractand intra-abdominal infections.

30

Pfizer

Pfizer’s anidulafungin (Ecalta®), for treatment
of invasive candidiasis, is the most widely-filed
antifungal.

Shionogi’s on-patent antibiotic cefiderocol(Fetroja®/Fetcroja®), used to treat infections
caused by aerobic Gram-negative bacteria when
there are few treatment options available, wasfirst approved by the FDA in 2019 and has not yet
been filed for registration in low- and middle-income countries. Cefiderocol was newly includedin the WHO 22nd Model List of Essential Medicines (EML) in 2021 as a ‘Reserve group’ antibiotic. In July 2021, Shionogi, the Global Antibiotic
Research and Development Partnership (GARDP)
and Clinton Health Access Initiative (CHAI)
announced a memorandum of understanding(MOU) to accelerate access to cefiderocol in lowand middle-income countries.

59

Appropriate access – registration

Antimicrobial Resistance Benchmark 2021

As a group, vaccines are more widely filed than medicines
Vaccines have a major role to play in curbing AMR, because they can decrease thenumber of cases of infectious diseases, and thus decrease antibiotic use. This slows
down the emergence and spread of AMR.5
Vaccines are more likely than medicines to be filed in a broad range of countries,
in part because many of them have been on the market for longer than on-patent
medicines. Vaccines can also represent a secure long-term financial opportunity forcompanies, because they cover broad populations (e.g. through national immunisation programmes) and can benefit from pooled procurement mechanisms such as
Gavi, The Vaccine Alliance. Pharma companies can also benefit from long-term patent protection for vaccines; some of the vaccines considered in this analysis werefirst approved more than 20 years ago.

FIGURE 44. Which on-patent vaccines are filed most widely?
This figure shows in how many of the 102 countries each on-patent vaccine is filed for registration.

Pneumococcal 13-valent (Prevnar 13®)
13®)
(Hexaxim®)
DTaP HepB IPV Hib (Hexaxim®)

GSK

45

GSK

31

(Boostrix®)
DTaP booster (Boostrix®)
DTwP HepB Hib (Shan5™)

23

Pfizer

22

GSK(Trumenba®)
Men B (Trumenba®)(Boostrix® Polio)
DTaP IPV booster (Boostrix®
Polio)

14

GSK

13

GSK

6

Pfizer

5

GSK

3

GSK

0

GSK

0

Pfizerunknown

MSD

unknown

MSD

unknown

0

10

20

Pfizer leads by filings its
pneumococcal vaccine,
Prevnar 13®, in 65 of the
102 countries. Pfizer is followed by Sanofi’s hexavalent and meningococcal
vaccines, filed in 54 and 48
countries respectively.

Sanofi19(Menveo®)
Men A,C,Y,W-135, (Menveo®)(Infanrix® IPV
DTaP IPV Hib (Infanrix®
IPV Hib)
Hib)

PedvaxHIB®)HepB DTaP HepB (Liquid PedvaxHIB®)(Pneumovax® 23)
Pneumococcal 23-valent (Pneumovax®
23)

Sanofi48(Infanrix® Hexa)
DTaP HepB IPV Hib (Infanrix®
Hexa)(Nimenrix®)
Men A,C,Y,W-135 (Nimenrix®)(NeisVac-C®)
Men C (NeisVac-C®)(Vaxelis®)
DTaP HepB IPV Hib (Vaxelis®)

Sanofi

54(Menactra®)Men A,C,Y,W-135 (Menactra®)(Synflorix®)
Pneumococcal 10-valent (Synflorix®)(Bexsero®)
Men B (Bexsero®)(Infanrix® Hib)
DTaP HepB Hib (Infanrix®
Hib)

Pfizer

65

30

40

50

60

70

Sanofi is the only company
to have registered all threeof its relevant vaccines,
Hexaxim®, Menactra® andShan5™, in at least one
low-income country each(including Chad, Nepal,and Haiti).

MSD

DTaP=Diphtheria, Tetanus, acellular Pertussis
DTwP=Diphtheria, Tetanus, whole-cell-pertussis
HepB=Hepatitis B
IPV=inactivated Poliovirus
Hib=Haemophilus influenzae type b
Men A,C,Y,W-135=Meningococcal serogroups A, C, Y, W-135
Men B=Meningococcal serogroup B
Men C=Meningococcal serogroup C

60

Appropriate access – registration

Antimicrobial Resistance Benchmark 2021

Which off-patent/generic products are filed most widely?

Methodology: products in this analysis

The Benchmark looks at the off-patent/generic medicines with the highest volume

Within each access category, each company’sof sales. The number of registration filings varies greatly by access category. Accessand watch antibiotics (defined according to the WHO’s AWaRe classification) are
filed for registration much more widely than reserve antibiotics (16 access countries
on average), because they are more widely used and represent a higher sales

top two off-patent products by sales volume
were selected for analysis, using IMS global sales
data.*
These categories are Access, Watch, Reserve(AWaRe), antifungals, and antituberculosis.
However, off-patent/generic TB medicines werevolume for companies.
Reserve antibiotics are largely overlooked by pharmaceutical companies.
Although they should only be used as an option of last resort and can thus repre-

removed from the analysis because they did notmeet current TB treatment guidelines.

sent fewer financial incentives for companies, reserve antibiotics are also essential
for controlling some of the most resistant pathogens. Yet, they are filed in only twoout of 102 access countries in scope on average.
Of the products in scope, only 39% of off-patent/generic medicines suppliedby large research-based companies are filed in more than 10 access countries. For
products in scope which are marketed by generic medicine manufacturers, that
number drops down to 29% filed in more than 10 LMICs.

FIGURE 45. Which off-patent/generic products are filed most widely?
Of the products in scope, these graphs show the five most widely filed off-patent/generic medicines
targeting bacterial and fungal infections, broken down per the AWaRe classification, as well as
antifungals.

Access Group

Watch Group‘Access’ antibiotics should be readily available, affordable and quality-assured.

Second-line treatments that should be prescribed only for specific

On average, the ‘Access’ antibiotics included in this analysis are filed in only

indications, since they are at higher risk of AMR. On average, the ‘Watch’

16 out of the 102 LMICs in scope.

antibiotics included in this analysis are filed in only 16 out of the 102 LMICs in
scope.

Amoxicillin/clavulanic acid (Novartis)

Cefuroxime (GSK)

60

64

Levofloxacin (Novartis)

58

62

Clarithromycin (Abbott)

58

Clarithromycin (Novartis)

56

70

Amoxicillin (Novartis)
Amoxicillin/clavulanic acid (GSK)Metronidazole (Sanofi)

48

Amoxicillin/clavulanic acid (Aurobindo)

Azithromycin (Pfizer)

35
0

20

40

60

80

0

48
40

20

60

Reserve Group

Antifungals

Last resort or third-line treatments that should be used when all others fail,

While these are not included as part of the WHO AWaRe Groups, they are

in order to limit the risk of resistance. On average, the ‘Reserve’ antibiotics

necessary to treat fungal infections. On average, the antifungal products inincluded in this analysis are filed in just two of the 102 LMICs in scope.

this analysis are filed in nine out of the 102 LMICs in scope.

80

Although they should only be used as a last resort option, they are alsoessential for controlling some of the most resistant pathogens.

Tigecycline (Pfizer)

Fluconazole (Pfizer)

24

Tigecycline (Novartis)

52

6

Voriconazole (Pfizer)

Polymixin B (GSK)4Voriconazole (Novartis)

17

Polymyxin B (Viatris)

2

Fluconazole (Cipla)

14

Fosfomycin (Cipla)

N.b., off-patent/generic products (suchas older antibiotics like amoxicillin) areoften produced and sold by multiple different companies, which means thatthe same product’s INN (International
Nonproprietary Name) can be registered
several times.

Itraconazole (Novartis)

1
0

31

20

40

60

80

* Sales volumes specific to low- and middle-income countries are not reflected in
global sales data.

11
0

20

40

60

80

61

Appropriate access – registration

Antimicrobial Resistance Benchmark 2021

How the companies compare in registering their on-patent products
The Benchmark looks at whether the companies are registering the patented products in their portfolios in the 102 LMICs in scope, and in how many of these countries they have filed for registration. The figures below show higher numbers of registrations for companies’ on-patent vaccine portfolios than for on-patent medicines,
with Pfizer performing strongly in both categories.
FIGURE 46. Registration filings for on-patent medicines, by company

FIGURE 47. Registration filings for on-patent vaccines, by

There are 17 on-patent antibacterials and antifungals covered by this analysis, marketed bycompany

seven companies. This figure shows the number of countries in scope in which each

There are 18 antibacterial vaccines covered by this analysis,company has registered at least one of its products.

marketed by four companies. This figure shows the number ofcountries in scope in which each company has registered at

Pfizer33

Johnson & Johnson

30

Viatris

27

MSD

25

Otsuka9

Cipla
Shionogi

Pfizer’s has five on-patent medicines inscope. Notably, Pfizer filed its reserve
antibiotic ceftazidime/avibactam (Zavicefta™) in 18 additional countries since2020, including three low-income countries (Ethiopia, Tanzania, and Uganda).
Zavicefta™ is used to treat complicatedintra-abdominal infections, cUTIs, andhospital-acquired pneumonia.

1
0
0

20

40

Generic medicine manufacturer
Cipla registered its newly-acquired
on-patent medicine plazomicin(Zemdri®) in India. This reserve antibiotic is used to treat complicatedurinary tract infections.

60

80

Johnson & Johnson has only one
eligible on-patent medicine, bedaquiline (Sirturo®), but has filed forregistration in 30 countries.

least one of its products.
Pfizer68

Sanofi

59

GSK

46

MSD

unknown0
Sanofi has registered at least
one of its threeon-patent vaccines (Hexaxim®,
Menactra® andShan5™) in 59
countries.

20

40

60

80

Four of Pfizer’s on-patent vaccines
target a disease in scope. Of thesefour, its most widely filed vaccine is thePneumococcal Conjugate Vaccine (13valent) Prevnar13®, which is filed in 65
LMICs.

How the companies compare in registering their off-patent/generic medicines
The generic medicine manufacturers in scope have larger portfolios of off-patent/
generic medicines that qualify for analysis than the large research-based companies. However, looking at the products in scope, the large research-based compa-

GOOD PRACTICE

nies file each of their off-patent medicines more widely (in 52 of the 102 LMICs, on

Viatris: TB medicine pretomanid

average) compared to the generic medicine manufacturers (34 on average).

In 2020, Viatris newly filed its TB medicine pretomanid for registration in 23

FIGURE 48. Registration filings for off-patent/generic medicines, by companyof the LMICs in scope. Pretomanid was

There are 131 off-patent/generic medicines covered by this analysis, marketed by 16 companies. Thisdeveloped by the TB Alliance and isfigure shows the number of countries in scope in which each company has registered at least one of its

approved by the FDA and the EMA for

products.

the treatment of extensively drug resist-

Novartis

74

GSK

Among the generic medicine manufacturers in scope, Abbott has filed
its off-patent/generic medicines in
the highest number of LMICs.

67

ant TB (XDR-TB), as well as for treatment-intolerant/non-responsive multi-drug resistant TB (MDR-TB), as part of

Pfizer62

Abbott59

a six-month ‘BPaL’ oral treatment regi-

Sanofi56

men that combines bedaquiline, preto-

53

manid, and linezolid. WHO recommenda-

Johnson & Johnson
Aurobindo

tions for the use of pretomanid and the44

Sun Pharma

BPaL regimen currently apply only under

34

Cipla

30

Fresenius Kabi

29

Viatris

20

Teva

20

Shionogi

1MSD

unknown

Alkem

unknown

Hainan Hailing

unknown

0

20

40

60

80

Shionogi’s off-patent medicines, theantibiotics flomoxef and cefcapene,
are only approved in China. These
two medicines did not meet all regulatory requirements as their respective clinical trials were conductedprior to the ICH guidelines. Shionogi does not actively promote these
medicines. However, in July 2021,
GARDP identified flomoxef as apotential treatment option for neonatal sepsis.

operational research conditions. One of
the countries where Viatris filed pretomanid for registration is India, a country
with a high burden of TB. The company
took this step less than one year after
receiving its initial FDA approval, demonstrating a focus on filing for registration
across a wider range of countries.

62

Antimicrobial Resistance Benchmark 2021

APPRO PRIATE ACCESS – ACCESS STR ATEG I ES

What are companies doing to expand accessto antibiotics and antifungals in LMICs?
More than 80% of people alive today live in low- and middle-income countries

Strategies for vaccines vs medicines(LMICs). They face some of the highest burdens of infectious diseases, and some

When it comes to ensuring access to vaccinesof the highest rates of drug resistance, but often do not have access to the medicines and vaccines they need. Whether they can access these medicines and vaccines depends on several factors, including whether – and how – pharmaceuticalcompanies work to make their medicines and vaccines more available, accessible,

rather than medicines, different strategies arecommonly used. Many vaccines are purchasedin bulk by multilateral organisations on behalf ofgroups of buyers, usually national governments.
The same ‘pooled procurement’ approach isoften used for medicines for diseases such as

and affordable.
Across the 17 companies in scope, the Benchmark examined 166 antibacterial

HIV/AIDS, malaria and tuberculosis.

and antifungal medicines and vaccines. Looking at these products, the Benchmark
considered companies’ efforts to identify the greatest needs for their products, andany gaps in accessibility. Companies were assessed on how they set prices, bothat country level and for different populations within each country. In addition to

Products in scope for this analysis

assessing pricing strategies such as tiered pricing and donations, the Benchmark
considered other strategies to expand the accessibility of products. The Benchmark
also looked for evidence of patient reach for each access strategy reported by theOn-patent
vaccines

companies.

18 17

On-patent
medicines

166
products

131
Off-patent/generic
medicines
KE Y Q U ESTI O N S
What types of access strategies

Where are access strategies being

Are companies taking account of

Are companies reporting how

are pharmaceutical companies

put into action?

people’s ability to pay?

many patients their strategies areusing?

Strategies can be applied either

Globally, medicine is the largest

reaching?

There are several types of accesslocally, at the national level,

household expenditure after food.

Per access strategy, companies

strategies. Three key strategies are:or regionally. The Benchmark

Healthcare costs can push fami-

should prioritise populations with

1) pricing actions, such as not-for-assesses whether countries withlies into bankruptcy. Companies

the biggest need, and monitor theirprofit pricing or price caps; 2) vol-the highest need for better accesscan use a range of measures tosuccess at reaching patients.

untary licensing, which can boost

are being targeted.

assess the affordability of a specificcompetition and supply; and 3)

price-point.

product donations.

CO N S I D E R ATI O N S
Product and geographic coverage

Affordability

Supranational procurement

Donations

Most of the access strategies

To address affordability more effi-

Access strategies for supranation-

Five companies report making

reported focus on a small set ofciently, companies should look atally procured products are gener-

donations of their antibacterial andcountries and products. Companies

implementing price reductions

ally better structured and applied

antifungal medicines: GSK, Pfizer,

need to be more transparent withor price segmentation (such as

more widely. Pentavalent andSanofi, Teva and Viatris. Producttheir strategies and cover a wider

second brand approach, price caps

pneumococcal vaccines, as well as

donations involve a few Accessrange of countries, people, andor patient assistance programmes)

the TB medicines in scope, are pro-and Watch antibiotics or antifun-

treatments. Local access initia-

in more countries, especially

cured through organisations includ-gals. Product donations continue

tives are still driving access overall,

low-income countries.

ing Gavi, The Vaccine Alliance andto play an important role in elimi-

and should be sustainable on the

the GDF Stop-TB Partnership andnating, eradicating, or controlling

long-term.

distributed to a wide range of eligi-

some diseases that affect popu-

ble countries.

lations living in LMICs. For people
living in poverty, donations may betheir only chance of getting accessto the treatment they need.

63

Appropriate access – access strategies

Antimicrobial Resistance Benchmark 2021

Many ways for companies to improve local availability, yet few are being used

What is the ‘gold standard’ for access

There are a wide range of tools available to pharmaceutical companies to increasestrategies?

local availability of vital antimicrobials in poorer nations. With each medicine or vaccine, pharmaceutical companies should consider the full range of access strategies
in the toolkit to work out what is most useful.
However, as identified in the 2018 and 2020 Benchmarks, companies are making minimal use of the many access strategies in the arsenal. This is the case both interms of the proportion of products covered by access strategies, and in terms ofthe countries that are being targeted.

Companies take a proactive approach and show
willingness to reach more people with their medicines and vaccines in LMICs, including countries
particularly affected by the relevant disease(s).
Companies are using and combining a rangeof strategies. Access strategies are clear, welldescribed, and detailed – specifying patient andgeographic reach, and considering ability to pay
where appropriate. Companies commit to longterm access plans.

FIGURE 49. Number of products covered by at least one access strategy, broken
down by category
Of the 166 products examined by the Benchmark, 54 are covered by at least one accessstrategy. A wide range of strategies count towards this figure, including donations, patient
assistance programmes, voluntary licensing, tiered and equitable pricing policies

On-patent medicines

7

On-patent vaccines

13 5

10

Off-patent/generic medicines

34
0

Covered by at least one
access strategy

97
50

100

Seven of 17 on-patent medicines in scope arecovered by at least one access strategy. Theseseven products are marketed by five companies: Johnson & Johnson, MSD, Otsuka, Pfizer
150 and Viatris.

Not covered byaccess strategy, or
coverage is unknown

64

Appropriate access – access strategies

Antimicrobial Resistance Benchmark 2021

Pharma companies use a range of access strategies, but not for many products
The 17 companies in scope report various access strategies which apply to theirproducts. However, these are not comprehensively used.
In the case of on-patent medicines and vaccines, large research-based companies hold the key to access, and can unlock access by using strategies such as public/private partnerships, equitable and tiered pricing, voluntary licensing agreements, patient assistance programmes, or donations.
Both large research-based companies and generic medicine manufacturers canplay an important role in maximising the availability of essential off-patent/generic
medicines. They report doing so through competitive bidding, direct sales contracts, or through mandatory cost containment measures that apply to generic
medicines in many countries.
FIGURE 50. Number and type of access strategies being used for on-patent medicines
Of the seven companies with products in this analysis, five companies report using access strategies:*
Johnson & Johnson, MSD, Otsuka, Pfizer, and Viatris. This graph shows the types of strategies being
used to expand access to the 17 on-patent medicines.

Public/private partnerships

5

Equitable pricing policies

4

Patient assistance programmes

4

Donations2

Price caps

1

Voluntary licensing

1

Tenders

1
0

5

10

Of the 18 reported access strategies for on-patent products, 12
involve tuberculosis medicines.
Newer antibiotics and antifungals
are covered by only six of thesestrategies. Unlike TB medicines,
new antibiotics and antifungals areless likely to benefit from the support of pooled-procurement mechanisms, and rely mainly on companies actions to expand their accessin LMICs.

FIGURE 51. Number and type of access strategies being used for off-patent/generic medicines
Of the 16 companies with products in this analysis, 13 companies report using access strategies: Abbott,
Aurobindo, Cipla, Fresenius Kabi, GSK, Johnson & Johnson, MSD, Novartis, Pfizer, Sanofi, Sun Pharma,
Teva and Viatris. This graph shows the type of strategies being used to expand access to the 131
off-patent/generic medicines.

Tenders

8

Donations5

Public/private partnerships

3

Direct sales contracts

2

Patient assistance programmes

2
0

5

10

Across the 16 companies supplying off-patent/generic medicines
to low-and middle-income countries, three large-research based
companies (including Novartis andSanofi) and four generic manufacturers (Aurobindo, Cipla, Fresenius
Kabi and Teva) report participating in tenders in the public or private sector.

FIGURE 52. Number and type of access strategies being used for on-patent vaccines
All of the four companies with products in this analysis – GSK, MSD, Pfizer and Sanofi – report using
access strategies for these on-patent vaccines. This graph shows the type of strategies being used to
expand access to their 18 on-patent vaccines.

Tiered pricing policies

All four companies report using
tiered pricing policies. Tiered pricing
policies tend to apply globally, withpricing tiers defined by countries’
ability to pay.

6

Public/private partnerships

4

Tenders

2
0

5

10

* See appendix for definitions.

65

Appropriate access – access strategies

Antimicrobial Resistance Benchmark 2021

Do companies track how many people they reach with their access strategies?
The Benchmark looked for evidence of patient reach resulting from the accessstrategies employed by the companies.
Despite the strategies used, the burden of disease is still significant and not enoughpatients are reached. Many companies do not report the numbers, although companies are more likely to report their patient reach data for supranationally-procured
medicines and vaccines, and for off-patent/generic medicines with high volumes ofsales. Some medicines are still overlooked, such as the 23 off-patent reserve antibiotics in scope, for which no patient reach data was reported. However, some notable examples of patient reach can be provided for both on- and off-patent products.

EXAMPLES OF TRANSPARENCY ON PATIENT REACH
TB medicines distributed through the GDF-Stop TB Partnership
In 2020, at least 125,000 treatment courses of Johnson & Johnson’s bedaquiline(Sirturo®) were ordered through the GDF-Stop TB Partnership, and at least 25,000
treatment courses of Otsuka’s delamanid (Deltyba®) were distributed to more than
80 countries between 2016 and 2020. The GDF also supplied 400 treatment courses
of pretomanid (Dovprela) to 10 countries in 2020.
GSK: off-patent/generic medicines and on-patent vaccines
In 2020, GSK donated more than 200,000 units of its branded amoxicillin/clavulanic acid (Augmentin®) towards humanitarian relief efforts run by charitable organisations, including Save the Children. In 2020, GSK supplied 56 million doses of its
on-patent pneumococcal conjugate vaccine (Synflorix®) to Gavi-eligible countries.
GSK supplied 115,000 doses of Synflorix® to refugee programmes run by MSF in
Greece, Syria and South Sudan.
Pfizer: on-patent antibiotics and antifungals
In 2020, Pfizer reached 18,500 Brazilian and 2,500 Colombian patients with its
on-patent antibiotics ceftazidime/avibactam (Zavicefta™) and ceftaroline (Zinforo®).
In India, Pfizer reached 9,300 patients with Zavicefta™ and the antifungal isavuconazole (Cresemba®).
Cipla and Sun Pharma: off-patent/generic medicines
In 2020, Cipla distributed colistin in 500 Indian hospitals, treating 20,000 patientsin India per month. In South Africa, it provided access to azithromycin to 280,000
patients. In 2020 and 2021, Cipla participated in a tender to distribute more than one
million tablets of Q-TIB, a fixed dose combination used in tuberculosis prevention forpeople living with HIV, in seven LMICs including Haiti, Rwanda and Uganda. In 2020,
Sun Pharma estimates that it provided access to its amoxicillin/clavulanic acid to890,000 patients in 19 LMICs, including Cameroon, Myanmar, and Peru.

66

Antimicrobial Resistance Benchmark 2021

APPRO PRIATE ACCESS – CASE STU D I ES

What approaches are companies using to
improve access to specific medicines andvaccines?

When it comes to access to medicine, there is no ‘one-size-fits-all-products’
approach. For each product, pharma companies, often working with partners fromthe global health community, must build tailored approaches and take account of awide variety of factors. These range from commercial concerns such as patent status, and cover product characteristics – such as pack size, whether a vaccine needs
a cold-chain, or whether it needs to be administered by trained health professionals.
Importantly, the companies must address the needs and circumstances of specificpopulations, including their ability to pay. When the products in question are antimicrobials, the question of responsible use must also be front and centre of all decisions, to minimise the risk of drug resistance and ensure sustained effectiveness.
In this section, the Benchmark looks at examples of specific medicines and vaccines, some on-patent and some off-patent, to explore how pharmaceutical companies are expanding access to specific products.

CASE STU DY 1: I M PROVI NG ACCESS TO O N - PATE NT VACCI N ES
Products: 18 vaccines from four large

any other disease. Safe and affordable

programmes initiated by local govern-

research-based companies. These

vaccines are the best way to prevent

ments, such as in India or Thailand,

include vaccines against pneumococcal

these infections.6,7

often through a competitive bidding

disease, meningococcal disease, diph-

process with specific terms on prices,
How do LMICs typically gain access toquantities, delivery, and contract dura-

vaccines?

tion. In humanitarian emergencies,

Why do vaccines need a different

Vaccines are usually procured supra-

vaccines can be distributed throughapproach for improving access,nationally: they are purchased fromhumanitarian organisations, such ascompared to medicines?

multilateral organisations, such as

Médecins Sans Frontières (MSF).

Vaccines are a cornerstone of the mod-Gavi, The Vaccine Alliance, The Pan

ern health care system. Vaccination is

American Health Organization (PAHO),How are prices negotiated?

an important component of primaryand UNICEF. Gavi supports vaccines

Pneumococcal vaccine prices are nego-

health care and an indisputable humanagainst 17 infectious diseases, includ-tiated between companies and UNICEF

right. Vaccines are also an importanting pneumococcal conjugate vaccine

under the Advance Market Commitment

tool against antimicrobial resistance.

(PCV), in 57 countries, and has helped

and are made available to Gavi countries

Yet despite tremendous progress, farvaccinate more than 822 million chil-at a maximum price of $2.90 per dose.

too many people in the world - includ-

dren in the world’s poorest countries,

GSK and Pfizer have agreed to freeze

ing nearly 20 million young children

averting more than 14 million prevent-each year - still lack adequate access toable deaths.8 The Advance Market

prices for their pneumococcal vaccines(Synflorix® and Prevnar 13®) in Gavi-

vaccines. Most unvaccinated children

Commitment (AMC) for pneumococcal

graduated countries for up to 10 years

live in low- and middle-income coun-vaccines has enabled the procurement

after graduation. For most vaccines,

tries (LMICs), where health systems areof a total of 161 million doses of PCV forcompanies also apply tiered pricing poli-often under pressure. 17 million children

lower-income countries.

cies that allow them to adjust the prices

theria, tetanus, and pertussis.

of their vaccines to countries’ ability

missed out on life-saving diphtheria andtetanus vaccines in 2020, and pneumo-

Companies can also distribute their vac-

to pay, setting higher prices in middle-

nia kills more children each year thancines through national immunisationand high-income countries and offering

67

Appropriate access – case studies

Antimicrobial Resistance Benchmark 2021

lower prices in low-income countries.

a tiered pricing strategy for their vac-vaccines is usually complex. Gavi works

In LMICs not supported by pooled-pro-cines, which allows for pricing flexibility.

closely with its industry partners, includ-

curement mechanisms such as Gavi,

However, except for prices for pneumo-

ing GSK and Pfizer, to provide vaccines

PAHO or UNICEF, companies still havewith forecasts of up to five years fora responsibility to ensure that ability tococcal vaccines distributed through Gavi
(Synflorix® and Prevnar 13®), companies

pay is taken into account.9

do not yet transparently disclose thenies can improve production scale byprices of their vaccines in LMICs.

offering new packaging features with

How are companies involved?

large volumes. For their part, compa-

multi-dose vials. Improving the produc-

Companies play an active role in

How does this approach help ensuretion line can also reduce manufacturing

expanding access to their vaccines. All

supply can match demand?

costs and lead to lower selling prices.

vaccine manufacturers in scope apply

The development and production of

CASE STU DY 2: NOVARTIS’ APPROACH TO EXPAN D I NG ACCESS TO O FF- PATE NT M E D I CI N ES
Products: Amoxicillin and amoxicillin/

Details: Novartis, through Novartis

2022 and five-fold by 2025 through its

clavulanic acid, off-patent antibiotics

Access, Novartis Healthy Family and

SSA unit. In 2020, Novartis, throughproduced by Novartis

Novartis SSA, offers its generic antibac-

its Sandoz division, committed to sell-terial products at tailored prices to gov-

ing some of its medicines, including

How: Novartis uses equitable and com-ernments, non-governmental organisa-

antibiotics used to treat patients withpetitive pricing and participates intions and other institutional customers

COVID-19-related symptoms, at zero-tenders.

in lower-income countries. Novartis’s

profit to governments in up to 79 eli-access pricing policy means prices start

gible low-income and lower-middle-in-

Impact: Amoxicillin is used to treat aat USD 1 per treatment, per month. Its

come countries.

variety of common bacterial infections,

SSA unit takes a high-volume, low-priceNovartis participates in competi-such as pneumonia, dental abscesses,

approach to increasing patient reach. In

tive bidding. Tender prices are set using

and urinary tract infections.10 Novartis

2020, more than four million patients in

Novartis’s cost of goods with an addi-

reached more than 10 million people ineligible countries were ensured accesstional minimum acceptable margin, as

LMICs to date.

to amoxicillin through Novartis Accesswell as historical data and local insights

and Novartis Healthy Family. More thanfrom its customers. Making use of local

Where: Novartis Healthy Family pro-

1.7 million patients were ensured accessinsights may include considering thegrammes are active in India, Kenya,

to amoxicillin and amoxicillin/clavulanic

most recently awarded prices, the mostUganda and Vietnam.11 Novartis Sub-acid through Novartis SSA Unit in the

recently awarded companies, and the

Saharan African Unit (SSA) reaches 45

public sector.

maximum tender price set by the rele-of the countries in scope.

Novartis has publicly set a goal tovant National Health Insurance Scheme.

increase patient reach two-fold by

CASE STU DY 3: PFI ZE R ’ S DO NATIO N PROG R AM M ES FO R O FF- PATE NT M E D ICI N ES
Pfizer, Azithromycin (Zithromax®)
Donation programme

people have benefited from Pfizer’s

infections, such as cryptococcal men-donation programme. Pfizer extended

ingitis and esophageal candidiasis. Nine

Pfizer is part of the International

its donation programme until 2025, tocountries in scope are benefiting fromTrachoma Initiative (ITI), established inalign with WHO’s new target date ofthis donation programme, including

1998. In 2020, 31.1 million treatments

2030 for global trachoma elimination.

Botswana, Cameroon, Malawi, Rwanda,

were shipped to 12 countries throughSwaziland, and Lesotho.

tries in scope have been validated by

Pfizer, fluconazole (Diflucan®)Partnership programme

WHO as having eliminated trachoma as

Pfizer and its partners have distributed

a public health problem. These countries are Cambodia, China, Lao People’s

more than seven million doses of fluconazole (Diflucan®) to governments

Democratic Republic, Ghana, Mexico,and non-governmental organisations

Morocco, Myanmar, Nepal, and – most(NGOs) over the past two years to peo-recently – Gambia. More than 95 million

ple suffering from AIDS-related fungal

the ITI. As of April 2020, nine coun-

68Appropriate access – access strategies

Antimicrobial Resistance Benchmark 2021

CASE STU DY 4 : G E N E RIC M E D ICI N ES MAN U FACTU RE RS’ APPROACH TO EXPAN D I NG ACCESS TO OFFPATE NT/G E N E RI C M E D ICI N ES
Companies: Aurobindo, Fresenius Kabi,

pricing policies for its off-patent anti-

In many countries, generic medicinesTevabacterial and antifungal medicines in all

are subject to mandatory price control

sales segments and participates in ten-mechanisms, that result in lower prices

How: Aurobindo and Fresenius Kabi

ders in countries where its medicinescompared to originator medicines.

mainly distribute their off-patent/

are registered. Tenders can be an effec-

generic medicines through tenders ortive tool for governments to obtainand Direct Relief to donate antibiot-

direct-selling contracts. Teva stands out

discounts.

ics to paediatric immunocompromised

for its product donations.
Where: Global-scale, Malawi
Details: Aurobindo applies affordable

Teva is partnering with Global HOPE

Fresenius Kabi makes its genericcancer patients in Malawi. The goal of

medicines available in hospitals in thethe initiative is to treat 4,000 paediat-countries in which it operates, mainly

ric patients in Malawi over the next fiveby participating in tenders or throughyears.

direct sales contracts with hospitals.

CASE STU DY 5: EXPAN D I NG ACCESS TO TB M E D I CI N ES
Products:

128 countries have received drug-sen-

not approved by a Stringent Regulatory

MDR-TB* medicine bedaquiline(Sirturo®) – Johnson & Johnson

sitive TB medicines via the GDF since

Authority or the WHO Prequalification

its inception, reaching almost 34 million

Programme.

MDR-TB medicine delamanid (Deltyba®)

adults and 2.5 million children.12– Otsuka and Viatris

Viatris has agreed to donate 400
cumulative treatment courses of preto-

M/XDR-TB** pretomanid (Dovprela)

Where: Up to 150 countries and terri-manid directly to the Indian National– Viatris

tories – including all 102 LMICs in the

Tuberculosis Elimination Programme

Benchmark’s scope – are eligible for theand to the South African Conditional

How: Most TB medicines are procured‘access’ price for bedaquiline, delama-

Access Programme.

via the GDF-Stop TB Partnership, which

nid and pretomanid when procuring via

In April 2021, Viatris also launchedensures that national TB control pro-

GDF. Companies reported country-spe-a named patient access programme togrammes have uninterrupted access tocific donations and patient assistanceprovide access to individual patients inquality-assured medicines by providing

programmes (e.g., in India and South

countries where pretomanid is not yet

direct procurement services and secur-

Africa) and responding to both country

registered or available, free of charge

ing competitive prices, contingent on

and GDF global tenders.

or on par with GDF access pricing,

good stewardship practices. Companies

depending on eligibility.

can also use additional access strate-

Details:

gies to reach people in poorer coun-

GDF-Stop TB Partnership provides thetries directly, such as voluntary licens-

on-patent TB medicines in scope of theing agreements, patient assistance pro-Benchmark at defined global accessgrammes, or bidding in national tenders.

prices. Bedaquiline is priced at US$340
per six-month treatment course with

Impact: Since its creation in 2001, thean escalating percentage of free goods

Global Drug Facility (GDF) has facil-

depending on volume thresholds, result-itated access to TB medicines anding in a prorated price of US$272 perdiagnostics in more than 140 coun-six-month treatment in 2021. Per six-

tries, making quality-assured treat-month treatment-course, pretomanid

ments available to over 32 million peo-is priced at US$364, and delamanid at

ple with TB. GDF supplies longer and

US$1700.

shorter all-oral regimens for drug-re-Otsuka has geographically exclusive

sistant TB, and child-friendly medicines

licensing agreements with Viatris andfor both drug-sensitive and drug-resist-

R-Pharm. Viatris received a technol-

ant TB. GDF has secured price reduc-ogy transfer from Otsuka, allowing it totions of over 50% for most drug resist-produce delamanid in India. However,ant tuberculosis (DR-TB) medicines, pri-the delamanid produced by Viatris

marily by reducing risks to suppliers

does not currently meet quality assur-

and minimising their transaction costs.

ance requirements of donors, as it is* Multidrug-resistant tuberculosis** Multidrug- and extensively drug-resistant tuberculosis

69

Antimicrobial Resistance Benchmark 2021

APPRO PRIATE ACCESS – SU PPLY

What steps are pharma companies taking toensure continuous supply?
To reduce the threat of AMR, the right treatment must be used to treat the right

Supply chain challenges

type of infection. Yet antibacterial supply chains are complex and highly frag-Global antibiotic supply chains are highly frag-mented. Batches of medicines and vaccines pass through multiple distributors withlittle alignment to ensure continuous supply. These inefficiencies can lead to stockouts, while the fragmentation of the supply chain is a driving factor for shortages.
The Benchmark evaluates the steps companies are taking to deliver an uninter-stages of the chain, and very few at other vitalstages. Supply inefficiencies can be caused by
failures in manufacturing processes, scarcity ofactive pharmaceutical ingredients (APIs), theconcentrationof API
manufacturing in only aLarge R&D based
companies

rupted supply of quality products.

few countries (mainly India and China), pressure

FIGURE 53. What are companies doing to ensure a continuous supply of antibiotics, antifungals
and vaccines?

Generic medicine
manufacturers
on margins,and heavy
dependence on only one

or a few producers of some antibiotics.
Large R&D based companies

R&D
based
companies supply of theirThis table lists the priority activities for companies to help Large
ensuretheuninterrupted

products, along with examples of company activity in each area.

Generic medicine manufacturers

FO R EC A STI N G D E MAN D

mented, consisting of many players at someLargebased companies
S HAR
I NR&DG DATA

Large R&D based companies
Generic medicine manufacturers
Generic medicine manufacturers
based
MAILarge
NTAIR&DNIN
G B companies
U FFE R STO CK S

Large R&D based companies

Large R&D based companies
Generic medicine manufacturers

Large R&D based companies
Generic medicine manufacturers

Generic medicine manufacturers

Generic medicine manufacturers

Generic medicine manufacturers

Large
R&D basedacompanies
How:
To maintaincontinuous supply of prod-

Large
R&D basedcompaniesinformation withHow:
Companies
exchange

R&D based companies
How:Large
To mitigate
against shortages, companies

R&D basedcompanies
ucts,Large
companies
makeuse of short- and long-

Largestakeholders
R&D based companies
external(such as government min-R&Dabasedcompanies
can Large
maintainbufferstock of extra inventory interm forecasting mechanisms to ensure there

istries of health) to align supply with demand.

case of manufacturing delays or an unexpected

are sufficient APIs and finished products to meet

Example: Novartis ensures that forecasts for all

increase in demand.

future demand for those products.

countries are carried out according to a stand-

Example: Abbott maintains a buffer stock of crit-

Example: Aurobindo makes a monthly rolling

ardised - at least monthly rolling - process,ical APIs and finished goods that is reviewed

on a weekly basis. Aurobindo also uses long-weekly data exchange with its anti-infective

Generic medicine manufacturers
Generic medicine manufacturers
Large R&D based companies

Large andR&Dmonitors
based companies
forecast
supply in some countries
Generic medicine
manufacturers
Generic medicine manufacturers

range planning to provide medium- to longertermLarge
forecasts.
R&D based companies
Large R&D based companies
Generic medicine manufacturers

Generic medicine manufacturers
Generic medicine manufacturers
Large R&D based companies

R&D based companies
1-36Large
monthsin advance.
The company ensures
Generic
medicine
manufacturers

Generic medicine manufacturers

Generic medicine manufacturers
Large R&D based companies

Large R&D based companies
quarterly
andadjustedas needed.
Generic
medicine
manufacturers

Generic medicine manufacturers

Generic medicine manufacturers

Large R&D based companies

Large R&D based companies

stakeholders.

Large R&D based companies
Generic medicine manufacturers

Large R&D based companies
Generic medicine manufacturers

WO R KI N G WITH S E VE R AL API

C APACIT Y B U I LD I N G AN D/O R

M ITI GATI N G AGAI N ST SU BSTAN DAR D &SU PPLI E RS

TECH N O LO GY TR AN S FE RSFAL S I FI E D M E D I CI N ES

Generic medicine manufacturers

Generic medicine manufacturers

Large R&D based companies

Large R&D based companies

Large R&D based companies
Generic medicine manufacturers

Large R&D based companies
Generic medicine manufacturers

Generic medicine manufacturers

Generic medicine manufacturers
Large R&D based companies

No disclosure ofPartial decoupling of
information onsales incentives from
Generic medicine manufacturers
sales practices
sales volumes

Generic medicine manufacturers

How:NoCompaniesor mitigate
the prodisclosurepreventofPartial decouplingofLarge R&D
basedandcompanies
information
onmedicinessales
ductionor supply ofthat incentives
appear to fromufacturing
in lowmiddle-income countries
No disclosure ofPartial decoupling ofsales practices
sales volumes(LMICs),pharma companies
caninvestin capacinformationonsales
incentives
from be authentic, but are of low quality or contain
Generic medicine manufacturers
sales andpractices
sales volumes
replacement and/or non-working ingredients.
ity building
technology transfers– whereby
How: To support the development of local man-

Large
R&D basedcompanies
How:
To mitigate
againstshortages, companies

can Large
workR&D
withbased
several
API suppliers.
companies

Generic medicine manufacturers
Example:The APIs in Viatris’ products are
Generic
medicinesourcedfromthird manufacturers
parties or manufactured

skills, knowledge, technologies, and manufacturNo disclosureof with local
Partialdecoupling of
ing methods
are shared
manufacturLarge R&D based companies
information onsales incentives fromconsistingof more ofthan 40 locations
worldNo disclosure
Partial decouplingof ing partners.
sales practices
sales volumes
information
sales incentives
from Example: Otsuka is ensuring a technology transwide, including
for onthe antibacterial
and antifunGeneric medicine manufacturers
sales
practicessales
volumesgal agents in scope. The company registers sevfer to Viatris (previously Mylan) for delama-

Example: Sanofi has several structures, gov-

internally. Viatris has a global supply network

ernance and policies dedicated to fighting sub-eral of its products in multiple locations to mitinid (Deltyba®). The first phase of the technolof
decouplinggate Nothedisclosurerisk of shortages,
andPartial
to allow
flexibility of ogy transfer was completed in 2020, allowinformation onsales incentives froming Viatris to manufacture, package, and distribto meet demand.
sales practices
sales volumes
ute delamanid in its own access countries. The

work, a security department that helps detect

standard and falsified products. These include
a pharmaceutical crime investigation department, an anti-counterfeiting coordination netillegal sales on the Internet, and a dedicated central laboratory in France for analysis of falsification. If a substandard and falsified product issecond phase of the technology transfer for full

identified, it will be reported to the relevant local

API manufacturing is on-going and expected toauthorities within seven days and a market with-be completed in 2021. Following this technol-drawal may be decided. If necessary, doctors,

ogy transfer, Viatris’ manufactured delamanid

pharmacists and patients may also be informed.

has been made available in a number of LMICs,

Investigations and legal action may be taken to

including South Africa and India, and will beidentify the origin of the substandard and falsi-

available for procurement through the GDF fol-

fied product.

lowing WHO prequalification.

70

Appropriate access – supply

Antimicrobial Resistance Benchmark 2021

How are companies ensuring a continuous supply of their products in LMICs?

KE Y TE R M S

Accessibility relies on companies having strategies to ensure a continuous sup-A stockout occurs when a doctor or pharmacist
cannot dispense an antibiotic because there isply of antibacterial and antifungal medicines and vaccines, both on- and off-pat-no stock available in that location, at that time.

ent. To ensure an uninterrupted supply of high-quality products, companies needto prepare for stockouts by ensuring the supply of active pharmaceutical ingredi-

A shortage occurs when supply does not meetents (APIs), keeping sufficient buffer stock, and aligning with external stakehold-demand. Shortages can occur on a national level(i.e., when specific regions or countries cannot

ers on supply and demand. When people are assured of a continuous supply, thisbring in supplies for any reason), or at a global

decreases the chance they will resort to obtaining substandard or falsified medi-

level (i.e., when all countries struggle to accesscines and thereby increasing the risk of AMR.

the medicine).

FIGURE 54. What steps are pharma companies taking to ensure

FIGURE 55. Focus on different strategies tocontinuous supply?

mitigate against risk of shortages

This table shows the activities which the companies report using to ensure

This figure shows three approaches used by thethe uninterrupted supply of their products.

companies to reduce the risk of shortages, andhow many companies use each one.

Capacity buildDemand planning ing and/or techand data sharing nology transfers
activities
inititiaves

Strategies tomitigate against
substandard
and falsified
medicines

17 companies

5

Strategies tomitigate against
risk of shortages

Managing
a buffer stock

128

Working withseveral API
suppliers9Large research-based companies
GSK

●

●

●

●

Johnson & Johnson

●

●

●

●

MSD

●

●

●

Novartis●●●

Otsuka●●●Pfizer

●

●

●

● 12

Sanofi●●●●Shionogi

○

●

●

○

17 companies

●
●
●

5

Managing
a buffer stock

8

Working withseveral API
suppliers

9

8

Auditing
stocks9

Generic medicine manufacturers
Abbott

●

●

Alkem

○

○

Aurobindo

●

●

Cipla

●

●

Fresenius Kabi●●

17 companies●○Managing5
a buffer stock
●
12 ●
●

●
○
●
●
●

Hainan Hailing

○

○

○

○

Viatris

●

●

●

●

Sun Pharma

●

○

●

●

Teva

●

○

●

●

● Activity reported ○ No activity reported

8
9Working withseveral API
suppliers

8

Auditing
stocks9

Sanofi has publicly set a “zero outof stock” goal. The company has
a consistent safety stock policy toensure the right level of safety stock
in countries. Its supply chain data
is locally adjusted and adapted forlow- and middle-income countries.

71Antimicrobial Resistance Benchmark 2021

APPRO PRIATE ACCESS – TECH NO LOGY TR ANSFE RS

Companies carry out global tech transfers as
isolated, yet valuable, initiatives
Medicines and vaccines are produced via sensitive, multi-stage, and highly technical

KE Y TE R M S

processes. To give an idea of the complexity, it can take more than a year to com-

Technology transfer

plete all manufacturing and quality steps for a single batch of vaccines. It is important that multiple manufacturers can master these processes – to make sure supply
can meet demand everywhere in the world, and to minimise the impact of a shutdown of a single manufacturing site. Further, when medicines and vaccines are produced locally, the shorter supply chains help lower the risk of regional shortages.
To support the development of local manufacturing in low- and middle-income
countries, pharma companies can invest in capacity building and technology transfers – whereby the skills, knowledge, technologies, and manufacturing methods areshared with local manufacturing partners.

A pharma company transfers knowledge about
the process to make a specific medicine or vaccine to a manufacturing site in a country wherethat product is needed, along with the technology necessary to manufacture it.
Capacity building
Building manufacturing or supply chain capacity by working with local partner manufacturers, distributors, and logistics providers to
identify bottlenecks and improve capacity for

Of the 18 on-patent vaccines included in this analysis, nine are subject to atechnology transfer initiative; by contrast, very few initiatives covering any of the
148 on-patent and off-patent medicines (antibiotics and antifungals) have beenreported to the Benchmark. Medicines which are covered by an initiative include
tuberculosis products, as well as some older antibiotics – including one ‘Watch’appropriate supply chain and manufacturing
management.
Local manufacturing sites
Pharmaceutical companies can invest in local
manufacturing facilities to produce raw ingredients and/or finished products, by financing andantibiotic.

building reliable infrastructures and helping staff

FIGURE 56. 10 pharma companies support local manufacturing projects across 14 LMICs

develop technical expertise.

Of the 17 companies covered by the Benchmark, 10 report that they are supporting local manufacturing(such as by carrying out technology transfers) in at least one of the 102 low- and middle-income
countries in scope. This map shows the countries where at least one project is taking place.

Brazil
GSK partners with three Brazilian state-owned
vaccine manufacturers to produce its priority vaccines, including antibacterial vaccines, locally in
Brazil. Three activites are covered by this technology transfer: 1) manufacturing pratices, suchas formulating and packaging; 2) technical knowhow; and 3) analytical testing methods. This technology transfer aims to upgrade the infrastructure, develop local manufacturing capabilities, andtrain employees in good manufacturing practices.
Brazil should be able to produce at least 60 million vaccine doses for its population each year.

Pakistan
In Pakistan, Novartis is partnering with local third
parties to produce some of its products locally,
including its Sandoz penicillin portfolio, and transfer manufacturing knowledge. This technology transfer aims to promote local manufacturing capacity, and to enable those manufacturing
sites to meet manufacturing practice standards,
improve levels of technical capability, and comply
with health, safety, and environmental (HSE)
regulations.

72

Appropriate access – tech transfers

Antimicrobial Resistance Benchmark 2021
A collaborative approach is needed

Zoom-in on technology transfers and manufacturing in Africa
Africa accounts for nearly 17% of the world’s population, but produces only 3% of
the medicines and 1% of the vaccines it consumes. Most of the medicines and vaccines distributed must be imported from producers in foreign countries such as
India and China, which means they pass through multiple distribution channels
and intermediaries. U​ p to half of the patients in Africa are estimated to lack accessto critical medicines.13 In sub-Saharan Africa, only Kenya, Nigeria, and South Africa
have a relatively sizeable industry, with several companies that produce for theirlocal markets and, in some cases, for export to neighbouring countries.14
Even though supply chains remain international and fragmented, and countries
may still need to source raw materials, active ingredients, or excipients from abroad,pharma companies can continue to build sustainable initiatives to enable morecountries and regions to produce their own medicines and vaccines locally in thelong term.

Lack of capability and training are significant
challenges. Companies that demonstrate bestpractice often partner with others, and/or open
their own offices locally. They also work withother stakeholders (such as governments andNGOs) to plan transfers of technology to enableproducts to be made sustainably.
Pharmaceutical companies’ decisions to transfer technology depends on a variety of factors,
such as finding a local partner, local politics andmarket environment, political stability, or good
regulatory standards. While low-income countries are not always able to meet these conditions, stable and industrialised upper-middle-income and lower-middle-income countries may
present an opportunity for successful technology transfer.21

FIGURE 57. Countries in Africa where technology transfers are being carried out
Seven of the 17 companies evaluated report that they are carrying out at least one technology transfer
project in at least one African country. These projects are spread across five countries.

MoroccoOne company, whose name cannot be disclosed,
is carrying out a technology transfer to a thirdparty manufacturer for the production of active
pharmaceutical ingredients (APIs) for antibiotics.
Morocco manufactures 70% of the pharmaceutical products it consumes, but depends largely on
foreign supply of raw materials, and imports morethan 90% to meet these needs.15

ZambiaViatris supports a manufacturing
facility in Zambia. In Zambia, home
to more than 17 million people17, theprivate pharmaceutical sector consists of local manufacturers, wholesalers, and retailers. Local manufacturing capacity is very small, andmedicines are mainly imported from
India.18

Burkina Faso
One company, whose name cannot be disclosed,
is carrying out a technology transfer to a thirdparty manufacturer for the production of APIs
for antibiotics. Burkina Faso is heavily reliant on
imported pharmaceutical products to meet theneeds of its population.16
Nigeria
Since 2008, Sanofi has been involved in technology transfers in Nigeria to produce some of its
medicines locally, including the antibiotic metronidazole (Flagyl®), which is on the WHO’s Listof Essential Medicines. The technology transfer
aims to enable the local manufacturing plant tomeet all quality standards and upgrade its capabilities. About 70% of the medicines used in Nigeria are imported from China and India.19

South Africa
Seven companies are involved in technology transfers
in South Africa. The country has a diverse economy
with an established and well-developed manufacturing base, which helps explain why it benefits fromthe most reported technology transfer initiatives.
However, although South Africa is an upper-middle-income country, it is a dual economy with one of
the highest persistent inequality rates in the world,
and thus remains an important focus for access to
medicine.20

South Africa
Pfizer is working with the South African government and Biovac Consortium Cape Town to produce its pneumococcal vaccine (Prevnar13®)
locally, from raw materials all the way through topackaged products. Pfizer has developed automated processes to standardise the complex formulation of the vaccine, which helps facilitate
the technology transfer and reduces manufacturing risks.

73

Antimicrobial Resistance Benchmark 2021

APPRO PRIATE ACCESS

Looking ahead

While the Benchmark identifies little forward movement on access to antimicrobials
and antifungals in low- and middle-income countries (LMICs), there are tangible
steps which companies can take. This page outlines what different groups ofstakeholders can do, from companies to governments.
CO M PAN I ESG OVE R N M E NT S

Registration• Build capacity within local regulatory health authorities to• Register medicines and vaccines more widely, or, whenstrengthen and expedite the processing of dossiers andapplicable, use an alternative option of special import waiv-

the approval of products, in order to encourage more com-ers in order to facilitate access.

panies to file products for registration. Participate in the• Focus on registering products in countries where the num-World Health Organization’s collaborative product assess-ber of registered products is the lowest, and where the bur-ment and regional regulatory harmonisation initiatives.

den of diseases is highest, in order to reach those who are• Support advocacy for increased transparency around whichmost in need.

products have been filed or approved for registration witha country’s regulatory health authority. Regulatory healthAccess strategies• Consider the full range of access strategies from the toolkit
to determine what is most appropriate, such as voluntary

authorities should make this information accessible themselves by publishing it in the public domain.
• Support the building of local manufacturing capacity tolicensing, partnering with external stakeholders, patientencourage technology transfers for the production of safe,

assistance programmes, and equitable pricing policies.

high-quality medicines and vaccines in LMICs. Create a sup-• Take affordability into account, ensuring that their medicines and vaccines are affordable to the most people,
including in the poorest countries.
• Set specific Key Performance Indicators (KPIs) to assess
the impact of access strategies, such as by measuring
patient reach.

portive environment for domestic industry.
• Where appropriate, participate in pooled procurement
mechanisms, (e.g., on a regional basis) in order to help
secure volume commitments and build stronger and more
enticing markets for companies.
• Support collaborative registration procedures and mechanisms such as the African Medicines Agency, to help

Ensuring continuous supply• Reduce the risk of shortages by aligning with external

streamline and expedite registration filings and approvals.
• Foster a stable market for, and support initiatives to ensure

stakeholders to keep sufficient buffer stocks, and by work-

appropriate access to, existing older off-patent antibiotics

ing with several API manufacturers to ensure non-inter-and antifungals. This will discourage companies from dis-

rupted supply. This will also help prevent substandard andcontinuing such products, many of which are still effective –falsified products from reaching LMICs.

but are not always available in LMICs.

• Build sustainable initiatives to enable more countries andregions to produce their own medicines and vaccines locallyover the long term, in the form of local manufacturing facilities, regional hubs, and technology transfers.

74

Antimicrobial Resistance Benchmark 2021

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Biotechs Are Saving the World fromSuperbugs. Can They Also Save
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2. Access to Medicine Foundation. 2020
Antimicrobial Resistance Benchmark Access to Medicine Foundation. Published2020. Accessed October 21, 2021. https://
accesstomedicinefoundation.org/publications/2020-antimicrobial-resistance-benchmark
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Methodology for the 2021 Antimicrobial
Resistance Benchmark - Access to
Medicine Foundation. Published 2020.
Accessed October 21, 2021. https://
accesstomedicinefoundation.org/publications/the-methodology-for-the-2021-antimicrobial-resistance-benchmark
4. Johnson & Johnson. Bedaquiline
Country Regulatory Status Overview.
Published 2021. Accessed October 21,
2021. https://www.jnj.com/_document/
bedaquiline-country-regulatory-status-overview?id=0000016e-0467-db13-a
9ef-566f1a520000
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D. The role of vaccines in combatting antimicrobial resistance. Nat Rev
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Vaccines and immunization. Published2021. Accessed October 21, 2021.
https://www.who.int/health-topics/
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accesstomedicineindex.org
8. Gavi The Vaccine Alliance. About
our Alliance. Published 2021. Accessed
October 21, 2021. https://www.gavi.org/
our-alliance/about
9. Gavi The Vaccine Alliance.
Pneumococcal vaccine support. Published2021. Accessed October 21, 2021.
https://www.gavi.org/types-support/
vaccine-support/pneumococcal

int/news-room/fact-sheets/detail/tuberculosis
13. Africa Resource Center. About Us,
Africa Resource Center. Published 2021.
Accessed October 21, 2021. https://www.
africaresourcecentre.org/about-us/
14. McKinsey & Company. Evaluating the
sub-Saharan African pharmaceutical market | McKinsey. Published 2019. Accessed
October 21, 2021. https://www.mckinsey.
com/industries/public-and-social-sector/
our-insights/should-sub-saharan-africamake-its-own-drugs
15. Health Action International WHO.
Medicine prices and access to medicines in the Eastern Mediterranean
Region Presentation of price information.
Published online 2008. Accessed October
21, 2021. http://www.haiweb.org/
16. Africa Resource Center. Strengthening
medicine supply planning in South
Africa during COVID-19. Published 2021.
Accessed October 21, 2021. https://www.africaresourcecentre.org/strengthening-medicine-supply-planning-during-covid19/
17. The World Bank. Zambia | Data.
Published 2021. Accessed October 21,
2021. https://data.worldbank.org/country/
zambia18. Handema R, Kandeke C, Lupuma
A, Lishimpi L, Yeta C. Measuring
Transparency to Improve Good
Governance in the Public Pharmaceutical
Sector ZAMBIA. Published online 2012.
19. Awucha NE, Janefrances OC, MeshachAC, Henrietta JC, Daniel AI, Chidiebere
NE. Impact of the COVID-19 Pandemic
on Consumers’ Access to Essential
Medicines in Nigeria. Am J Trop Med
Hyg. 2020;103(4):1630. doi:10.4269/
AJTMH.20-0838
20. The World Bank. South Africa
Overview: Development news, research,data | World Bank. Published 2019.
Accessed October 21, 2021. https://www.
worldbank.org/en/country/southafrica/
overview#1
21. International Federation of
Pharmaceutical Manufacturers &Associations. The Research-Based
Pharmaceutical Industry Experience.
Published online 2015.

10. NHS. Amoxicillin: antibiotic to treat
bacterial infections - NHS. Published 2021.
Accessed October 21, 2021. https://www.
nhs.uk/medicines/amoxicillin/
11. Novartis. Healthy Family Programs. Published 2021. Accessed
October 21, 2021. https://www.
novartis.com/esg/access/creating-sustainable-business-models/healthy-family-programs
12. World Health Organization.
Tuberculosis. Published 2021. Accessed
October 21, 2021. https://www.who.

75Antimicrobial Resistance Benchmark 2021

76

Antimicrobial Resistance Benchmark 2021

CO NTEX T

Stewardship

One of the main factors driving drug resistance is the misuse andoveruse of antibacterial and antifungal medicines. Specific strategies are needed to ensure such medicines are used only whenappropriate, in order to reduce opportunities for pathogens todevelop new ways of withstanding the medicines. While the success of these ‘stewardship’ strategies often depends on actions
taken by governments, prescribers and pharmacists, there is alsoa clear role for pharmaceutical companies. This role encompasses
how they package and sell their products, and how they carry out‘surveillance’ to track the emergence and spread of resistance.
Growing consumption drives resistance
Between 2000 and 2010, the consumption of antibiotics grew by more than a third
across 71 countries.1 This was mainly driven by increases in consumption in Brazil,
Russia, India, China and South Africa – countries which face some of the highest
rates of resistance.
Stewardship is needed worldwide
Robust safeguards to protect the effectiveness of antibacterial and antifungal medicines must be instituted worldwide to ensure that these medicines remain effective. For example, antibiotics should be prescribed only when needed, and certain
antibiotics should only be prescribed as a last resort.

H OW PHAR MA CO M PAN I ES C AN BO L STE R R ES PO N S I B LE US E O F TH E I R M E D I CI N ES

Surveillance

Sales practices

Conflict of interest

Adherence

Pharmaceutical companies

When sales agents’ bonuses

Pharmaceutical companies

The risk of resistance is kept

gather data that indicate

are linked to the quantity of

have a deep understand-to a minimum when patientswhere infection rates are ris-

antibacterial and antifungal

ing of how their medicines

can understand and adhere

ing, and where resistance is

medicines they sell, it acts as

can be used responsibly andto their courses of treatment

emerging. These insights are

an incentive for those agents

appropriately. Where com-until they are completed.

valuable puzzle pieces, par-to oversell. Companies canpanies contribute to educa-

Through the information

ticularly where they coverminimise the risk of over-tional activities for health-they provide on packaging

countries without national

selling by removing the linkcare professionals on how

and brochures – as well as

surveillance efforts. For

between sales volume andbest to manage the risk ofby wider campaigns to raise

example, they can inform thefinancial rewards, or evenresistance while using theirawareness of drug resistancetreatment guidelines used byby stopping the use of sales

products, they must also

– pharma companies candoctors when making clinicalagents for antibacterials andpro-actively avoid conflicts ofencourage the appropriate

decisions.

antifungals.

interest.

use of their medicines.

77Stewardship – context

Companies in scope

Antimicrobial Resistance Benchmark 2021
Companies in scope for Stewardship

The 2021 AMR Benchmark examines the policies and practices of eight large

Country
Large research-based companies

HQ

in supporting the appropriate stewardship of their medicines. By volume and value

1

GlaxoSmithKline plc

GBR

of sales, these are among today’s largest players in the global market for antibac-

2

Johnson & Johnson

USA

research-based companies and nine generic medicine manufacturers (see list, right)

terial medicines, together accounting for 29,031.60 SU million doses sold annually.*
This gives them significant opportunities to understand whether their products arebeing used appropriately and responsibly.
Countries in scope
In regards to stewardship, the geographic scope of the Benchmark’s analysis is3

Merck & Co, IncUSA

4

Novartis AG

CHE

5

Otsuka Pharmaceutical Co, Ltd

JPN

6

Pfizer Inc

USA

7

Sanofi

FRA

8

Shionogi & Co, Ltd

JPN

global.
Pathogens in scope
In terms of surveillance, the Benchmark highlights “priority pathogens” identified
as posing the greatest risk to human health from AMR. These are the bacteria andfungi identified by the World Health Organisation (WHO) and/or the US Centers for
Disease Control and Prevention (CDC) as priority R&D targets for limiting AMR.*** Source: IQVIA Midas 2017 anti-infectives data. Companies with sales volumes
below 1.000 SU million are not included inthis number.
** See appendix V.
*** Mylan has been renamed Viatris, following closing of merger with Upjohn, adivision of Pfizer, in 2020.

Generic medicine manufacturers
1

Abbott Laboratories

USA

2

Alkem Laboratories Ltd

IND

3

Aurobindo Pharma Ltd

IND

4

Cipla Ltd

IND

5Fresenius Kabi AG

DEU

6Hainan Hailing Chemipharma Corp Ltd

CHN

7

Viatris***

GBR

8

Sun Pharmaceutical Industries Ltd

IND

9Teva Pharmaceutical Industries Ltd

ISR

78

Antimicrobial Resistance Benchmark 2021

STEWARDSH I P – SU RVE I LL ANCE

Most companies support global efforts totrack the spread of resistanceIn order to control the spread of resistance, it is important to know where cases

Sharing consumption data is important inare occurring and where infection rates are rising. By monitoring resistance tooverall surveillance activities
Tracking and monitoring data on how antimicro-

treatment in patient populations around the world, the resistant strains can be
identified and their subsequent spread can be addressed. Efforts to collect data on
the emergence and spread resistance are termed ‘AMR surveillance’.
To date, AMR surveillance has primarily been the responsibility of governments.
However, pharmaceutical companies also have an important contribution to make.
Companies often have unique knowledge of resistance trends, which are particularly valuable where their data cover countries without national surveillance efforts.
In 2020, the Benchmark reported an increase in the number of surveillance programmes being run by the pharmaceutical companies in its scope. It also reported

bials are being consumed plays an important role
in reducing their misuse. Pharmaceutical companies can provide data to estimate consumption
through their imports, sales, donations and production records, and this can enhance national
surveillance of antimicrobial consumption.
Who is sharing consumption data?
• GSK periodically shares consumption data on
colistin and/or other antibacterial medicineswith the Pharmaceuticals and Medical Devices

that the majority of these programmes share their results publicly. In 2021, theAgency in Japan.

Benchmark again compares the surveillance programmes of the eight large
research-based companies in scope, and reports on whether they are active in the• Johnson & Johnson and Otsuka share someconsumption data on their MDR-TB medi-

surveillance of bacterial or fungal pathogens and/or infections anywhere in thecines bedaquiline (Sirturo®) and delamanid

world and whether these results are shared publicly.

(Deltyba®), respectively, with national and

As in 2020, the 2021 Benchmark examines the stewardship activities of generic
medicine manufacturers. However, these companies are not officially scored in thisinternational health organisations.
• Fresenius Kabi shares consumption data witharea, as they have thus far had a limited role in such activities.

national governments or other public healthauthorities, as appropriate. For example, it
shares sales data on meropenem in Latin

Most companies are engaged in AMR surveillance programmes

American countries.

As in the 2020 Benchmark, most companies are engaged in surveillance to someextent. Out of the eight large research-based companies, Otsuka remains the only
company not involved. Three generic medicine manufacturers, namely Abbott, Cipla
and Viatris, report that they are engaged in surveillance.
There are 19 programmes in which at least one company is engaged. Most of the
programmes cover at least one priority pathogen.*

FIGURE 58. How many priority pathogens do the programmes cover?

FIGURE 59. How engaged are the companies in AMR surveillance?

This figure shows the extent to which the programmes identified by the

The chart below shows how many of the 17 companies assessed are

Benchmark cover the surveillance of priority pathogens.*

engaged in AMR surveillance.

Programmes
covering
0 priority
pathogens

2

2

4
19
programmes
11

Programmes covering
12-17 priority pathogens
Programmes covering
6-11 priority pathogens

Programmes covering
1-5 priority pathogens
While most companies collect dataon pathogens targeted by theirown products, some companies go
beyond by also focusing on priority
pathogens*. These include Pfizer’s
ATLAS programme and CANWARD,
which is managed by the Canadian
Antimicrobial Resistance Alliance.

* Bacteria and fungi identified as priority R&D targets for limiting AMR, by the
WHO and/or the US Centers for Disease
Control and Prevention (CDC). See
Appendix V.

Company involvement:
AMR surveillance

7

10

involved in AMR
surveillance

Seven of the eight large researchbased companies support global
AMR surveillance efforts, with the
exception of Otsuka. Novartis is
newly involved in surveillance. Threeof the generic medicine manufacturers (Abbott, Cipla, Viatris) arealso involved in surveillance.

79

Stewardship – surveillance

Antimicrobial Resistance Benchmark 2021

Geographic coverage of surveillance is variable in Central Asia and Africa
Each surveillance programme covers a different geographic scope and range ofpathogens. There are many stakeholders around the world working to build as complete a picture as possible of where resistance is emerging, such as the WHO’s
Global Antimicrobial Resistance and Use Surveillance System (GLASS). Companies
can fund external programmes run by established institutions, and they can also run
their own surveillance programmes.
The first map below shows all countries covered by at least one of the 19 company programmes.
The two other maps below demonstrate, for two high-risk pathogens Candida
spp. and S. aureus, how company data can provide information and where gaps
remain in global surveillance.

FIGURE 60. Countries with at least one surveillance programme
Programmes running: 19
Companies involved: 10
High-income countries are consistently covered by surveillance
programmes, as are upper-middle income countries such as Brazil,
China and India. Coverage in lowand lower-middle income countries
in Central Asia and Africa, however,is more variable. For example, Iranis not covered despite having highrates of antimicrobial consumption as well as resistance against
pathogens including. E. coli and K.
pneumoniae.2,3
FIGURE 61. Countries with at least one surveillance programme covering Candida spp.
Programmes running: 3
Companies involved: 5
Candida spp. is a common causeof candidiasis. Notably, the entire
continent of Africa is not coveredby any programme across any of
the companies in scope, despite
increasing resistance rates of Candida spp. in Sub-Saharan Africa.4

FIGURE 62. Countries with at least one surveillance programme covering S. aureus
Programmes running: 10
Companies involved: 6
S. aureus is a common cause of skinand soft tissue infections. In contrast to programmes covering Candida spp., S. aureus is covered in a
few countries in Africa, but significant gaps remain.

* Bacteria and fungi identified as priority R&D targets for limiting AMR, by the
WHO and/or the US Centers for Disease
Control and Prevention (CDC). See
Appendix V.

80

Stewardship – surveillance

Antimicrobial Resistance Benchmark 2021

TABLE 8. Overview of surveillance programmes, broken down by company and bypriority pathogen
The table shows all 19 AMR surveillance programmes in which pharmaceutical companies
in scope are active, as well as which of the priority pathogens* are covered by eachprogramme. Enterobacteriaceae, P. aeruginosa, S. aureus and S. pneumoniae are thepriority pathogens most commonly under surveillance. The longest-running programme
has been active since 1992, while two new programmes have started since the 2020
Benchmark. The geographic range varies widely, from 1 to 81 countries.

‘Critical’ and/or ‘Urgent’
pathogens‘Medium’;‘Concerning’
and/or
‘Watch’pathogens‘High’ and/or ‘Serious’
pathogens

Streptococcus (group A)

Streptococcus (group B)

Haemophilus influenzae type b (Hib)

2007

1

13

● ○ ● ● ● ○ ● ● ○ ● ● ● ● ● ●●Candida spp.

Abbott; MSD; Pfizer

Streptococcus pneumoniae

CANWARD

Salmonella spp.

●

Staphylococcus aureus● ● ● ● ● ● ● ● ○ ○ ● ● ○ ● ●Mycobacterium tuberculosis

13Enterococcus spp.

81

Campylobacter spp.

Acinetobacter spp.

2004

Enterococcus faecium

Priority pathogens covered

PfizerPseudomonas aeruginosa

Geographic scope / number ofcountries

Antimicrobial Testing Leadership And
Surveillance (ATLAS)Enterobacteriaceae

Start
year

Neisseria gonorrhoeae

Companies active

Clostridioides difficile

AMR surveillance programme

SENTRY Antimicrobial Surveillance Program

Cipla; Pfizer; Shionogi

1997

57

11

● ○ ● ○ ● ○ ● ● ○ ○ ● ● ● ● ●●Study for Monitoring Antimicrobial Resistance
Trends (SMART)

MSD

2002

63

8

● ○ ● ○ ● ○ ● ● ○ ○ ● ● ○ ● ○○Study of Bacterial Resistance Kinki Region ofJapan

Shionogi

1997

1

8

● ○ ● ○ ● ○ ○ ● ○ ○ ● ● ● ● ○○BSAC Bacteraemia Resistance Surveillance
Programme

MSD; Pfizer

2000

2

7

○ ○ ● ○ ● ○ ○ ● ○ ○ ● ● ○ ○ ●●Abbott Restora Infectious Diseases ScientificExcellence (ARISE)

Abbott2019

1

5○ ○ ● ○ ● ○ ○ ○ ○ ○ ● ○ ○ ○ ●●Data Development

Viatris

2019

1

5

○ ○ ● ● ● ○ ○ ○ ○ ○ ● ○ ○ ● ○○Surveillance of Tedizolid Activity andResistance (STAR)

MSD

2011

14

5

○ ○ ○ ○ ○ ○ ● ● ○ ○ ● ○ ○ ○ ●●National Reference Centre for the Diagnostics
of Central Nervous System Bacterial Infections(KOROUN)

Novartis

2019

1

4

○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ● ○ ● ●●Shionogi Japanese surveillance studies
Programme

Shionogi

1992

1

3

○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ● ○ ○ ○ ●●SIDERO-WT Programme

Shionogi

2014

13

3

● ○ ● ○ ● ○ ○ ○ ○ ○ ○ ○ ○ ○ ○○Program to Assess Ceftolozane/Tazobactam
Susceptibility (PACTS)

MSD

2011

29

2

○ ○ ● ○ ● ○ ○ ○ ○ ○ ○ ○ ○ ○ ○○Survey of Antibiotic Resistance (SOAR)

GSK

2002

43

2

○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ● ○ ● ○○Drug Resistance Emergence Assessment in
MDR-TB (DREAM)

Johnson & Johnson

2015

11

1

○ ○ ○ ○ ○ ○ ○ ○ ● ○ ○ ○ ○ ○ ○○Pretomanid Resistance Surveillance Program

Viatris

2020

8

1

○ ○ ○ ○ ○ ○ ○ ○ ● ○ ○ ○ ○ ○ ○○Observatoires Régionaux du Pneumocoque(ORP)

Sanofi2000

1

1○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ● ○ ○ ○○China-based antibiotic resistance surveillance
programs (CHINET) / CHIFNET

Pfizer2005

1

0● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●Three Academic Societies Joint Antimicrobial
Susceptibility Surveillance Program

Shionogi

2004

1

0

● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● Applies ● Unknown ○ Does not apply* Bacteria and fungi identified as priority R&D targets for limiting AMR, by the
WHO and/or the US Centers for Disease
Control and Prevention (CDC). See

Appendix V. Priority bacteria and fungithat are not covered by surveillance programmes are not listed in this table. These
are: Bordetella pertussis, Helicobacter

pylori, Salmonella non-typhoidal & serotype typhi, Shigella spp., Aspergillus fumigatus and Candida auris.

81

Stewardship – surveillance

Antimicrobial Resistance Benchmark 2021

SURVEILLANCE PROGRAMMES THAT STAND OUT
Programme: ATLAS
Company: Pfizer

Pfizer expanded its ATLAS programme

Priority pathogens identified by WHO

Pathogens: 13 priority pathogens

to include more priority pathogens andand/or the CDC are known for lead-

Countries: 81

more countries through the Surveillance

ing to resistant infections and deaths.

Scope: Resistance against Pfizer’s anti-Partnership to Improve Data for Action

According to the CDC, more than 3.1

bacterial & antifungal medicines

on Antimicrobial Resistance (SPIDAAR),

million infections caused by priority

Data-sharing: Raw data is publicly

a new collaboration with the govern-

pathogens occur in the US each year,

availablements of Ghana, Kenya, Malawi andand more than 49,000 people die as

Uganda. Raw data (from 2018) is availa-

a result.4 Out of all surveillance pro-ble for download on the AMR Register,grammes from companies in scope,

which is an open-access data platform.

ATLAS and CANWARD both coverAggregated results (of antibacterial andthe most priority pathogens, however

antifungal resistance data) are shared

ATLAS has a broader geographic scopeon the ATLAS website, which is also anthan CANWARD.

open-access data platform, as well as
through open-access journal articles.

Programme: SENTRY
Companies: Cipla; Pfizer; Shionogi

SENTRY is a multinational programme

than 34,000 hospitalisations and 1,700

Pathogens: 11 priority pathogens

managed by JMI laboratories and sup-deaths in the US in 2017.5

Countries: 57

ported by several companies in scope.

The managing partner, JMI laborato-

Scope: Changes in resistance patterns

This programme is one of three whichries, publicly shares aggregated resultsover time, worldwide

cover Candida spp., a fungal pathogen

on the SENTRY website, as well as

Data-sharing: Aggregated results arewhich is estimated to have caused morethrough open-access journal articles.

Company: MSD

One of the priority pathogens cov-

MSD shares the aggregates results in

Pathogens: 8 priority pathogens

ered by SMART is S. pneumoniae, which

open-access journal articles, as well asCountries: 63

causes pneumococcal disease, ranging

on the online SMART database, which is

Scope: Respiratory, complicatedfrom ear and sinus infections to pneu-

restricted and cannot be accessed with-intra-abdominal and urinary tract infec-

monia and bloodstream infections.

out registration.

tions, and bloodstream isolates

S. pneumoniae is estimated to have

Data-sharing: Aggregated results arecaused 900,000 infections and 3,600

publicly available

deaths in the US in 2014.5

publicly available

Programme: SMART

Programme: CANWARD
Companies: Abbott; MSD; Pfizer

CANWARD is a national programme

The managing partner, the Canadian

Pathogens: 13 priority pathogens

focused on 13 priority pathogens. In

Antimicrobial Resistance Alliance, shares

Countries: Canada

Canada, it was estimated that resistantaggregated results of the CANWARD

Scope: Pathogens isolated in Canadian

infections contributed to 14,000 deaths

programme on an open-access data plat-hospitals

in 2018.6

form, as well as through open-access

Data-sharing: Aggregated results arejournal articles.

publicly shared82

Antimicrobial Resistance Benchmark 2021

STEWARDSH I P – SU RVE I LL ANCE

Slow progress and varied strategies for data
sharing
Making surveillance results – and, most importantly, raw data – publicly available is

How governments and industry can work

key to helping governments, public health authorities and healthcare profession-

togetherals (HCPs) measure and respond to the spread of resistant infections, analyse local
trends and prioritise objectives in stewardship policies. The Benchmark looks for

AMR surveillance is a largely neglected branchof public health. While the Benchmark recognises that action from pharmaceutical compa-

companies to share raw data so that the WHO, third-party researchers and othernies is needed, this can be achieved more effec-

experts have the information needed for further research, beyond the specifictively if countries are also active in setting up
surveillance systems, identifying gaps and set-questions asked by the companies themselves.

ting guidelines to harmonise the data.

The Benchmark notes that companies are using different mechanisms to makeTransparency in sharing surveillance data issurveillance data available. For example, Johnson & Johnson is sharing data fromclinical trials in the YODA platform which can only be accessed via approval throughan independent scientific committee, while MSD is reportedly preparing to hostbeneficial to public health authorities as it canhelp healthcare professionals to make informed
treatment choices, forecast disease trends, andplan medicine purchases. It can also be used to

its raw data on its website, with a process for researchers to request access.
However, data shared in a restricted manner has limited use as it is not freely available to public health bodies, which may not be able to predict which analyses might
be needed in the future. Furthermore, such data has a public health importance andshould therefore not be withheld.

inform policy directives and investment decisions, including diagnostic laboratory capacity
and infection prevention and control responses,
or identifying new emerging pathogens. It is
important that all stakeholders work collaboratively and in solidarity to coordinate and scale up

Although GSK and Shionogi have both pledged to share raw surveillance data

AMR surveillance.

publicly, there is no progress to report at the time of writing. Novartis and Sanofi
have started sharing surveillance data since the previous Benchmark report in
2020, having published aggregated results of their surveillance studies in open-access journal articles. Pfizer remains the only company in scope to reach the gold
standard by publicly sharing its raw data. It shares raw data from its ATLAS programme (from 2018) on the AMR Register, an open-access data platform.

Raw data shared via
open-access data platforms

FIGURE 63. Surveillance programmes share data in
different ways
This figure shows the data-sharing practices of the 19

4

surveillance programmes in which the 10 companies
take part. The majority of programmes publish theirresults in an aggregated form. Only one programmeshares raw data via an open-access platform.

Data notsharedpublicly

1

2

19
programmes

Aggregated results shared via
open-access data platforms
Aggregated results sharedin open-access journal
articles12

FIGURE 64. Best practice: AMR surveillance data sharing
BEST PRACTICE
1 company publishes

6 companies publish

4 companies publish

1 company publishes

1 company publishes raw

aggregated results via data

aggregated results via

aggregated results via

clinical trial raw data

data via open-access data

platforms in a restricted

open-access journal articles

open-access data platforms

via data platforms in aplatforms

mannerAbbottrestricted manner
GSK

AbbottMSD

MSD

Novartis

Pfizer

PfizerShionogi

Johnson & Johnson

Pfizer

SanofiShionogi

83Antimicrobial Resistance Benchmark 2021

STEWARDSH I P – SALES PR ACTICES

Overall progress in sales practices,
especially among generic medicine
manufacturers

When sales agents’ bonuses are linked to how much antibacterial and antifun-

KE Y TE R M S

gal medicine is sold, this acts as an incentive for these staﬀ to oversell in order to

Decoupling incentives from sales

increase their own pay. Companies can minimise the risk of overselling by removing
the link between sales volume and financial rewards, or – going further – by stopping the use of sales agents for antibacterial and antifungal medicines altogether.
In 2020, the Benchmark reported progress in this area, namely a jump from fivecompanies to ten companies that stopped the use of sales agents altogether, or are
decoupling bonuses from sales volume of antibacterial and antifungal medicines.
In 2021, data shows that more generic medicine manufacturers are taking action
to combat overselling with three additional companies putting policies in place,
namely Abbott, Aurobindo and Viatris. Moreover, among the large research-based
companies, Sanofi updated its policies around promotion of its antibacterial andantifungal medicines outside of its home country, France. However, progress in
improving sales practices is not always consistent, and company behaviour aroundpromotion can quickly change, so complacency should be avoided.

Full decoupling means that no component of asales agent’s incentives is linked to that agent’s
volume of sales. Partial decoupling means thata proportion of the agent’s pay is variable anddepends on incentives linked to sales volumes.
Percentage of variable pay
Variable pay can be linked to performance targets (related to behaviour or education) or sales
volumes. The higher the percentage of variable
pay linked to sales volumes, the more incentive
there is to increase sales volumes.
Level of incentives
Incentives for sales agents can be awarded at
individual, smaller group or national level. When
incentives are awarded at national and smaller

FIGURE 65. How far do companies go in decoupling performance incentives from sales volumes?
The charts show how many of the 17 companies in scope are addressing this issue, compared with howthey performed in the 2020 Benchmark.
Large research-based companies (8)
4
1

1

5

Sanofi progressed from non-disclosure of information in 2020, to not
deploying any sales agents to promote
its antibacterial and antifungal medicines to HCPs outside of France.

1

1

1

1

1

2020 2021

2020 2021

2020 2021

2020 2021

2020 2021

No disclosureof information
on salespractices

Partialdecoupling ofsales incentives
from sales
volumes

No promotion /full decouplingof someproducts
OR in somegeographies

Full decouplingof salesincentives fromsales volumes

No promotionof antibacterial
and/orantifungal
medicines to
HCPs

3

0

individual agent sells a higher volume of products, this does not directly increase that person’s
total pay.

D I FFE R E N CES B E T WE E N CO M PAN I ES
Large research-based companies and generic
medicine manufacturers operate in diﬀerent
ways, which can have an impact on sales andpromotional practices.
• Large research-based companies mostly
focus on developing new, innovative medicines.
These are typically promoted after receiving
implemented in daily medical practice, treatment

Since 2020, Cipla no longer
fully decouples. However, it
decouples incentives for sales
agents from sales volumes formore than 99% of their entire
total pay.
1

linked less directly to total pay, so that when an

market approval because they still need to be

Generic medicine manufacturers (9)6group (rather than individual) level, they are

guidelines or medical formularies.
• Generic medicine manufacturers are focused4

on producing and manufacturing generic medi-

Three companies havestarted disclosing theirsales practices.

1

cines that are launched after the patent on innovative medicines has expired, with the exception of when production of an on-patent product

1

0

1

1

2020 2021

2020 2021

2020 2021

2020 2021

2020 2021

No disclosureof information
on salespractices

Partialdecoupling ofsales incentives
from sales
volumes

No promotion /full decouplingof someproducts
OR in somegeographies

Full decouplingof salesincentives fromsales volumes

No promotionof antibacterial
and/orantifungal
medicines to
HCPs

is licensed to that manufacturer. Generic medicines, with the exception of branded generics,
are typically not promoted on a product level as
the product is already implemented in daily practice. However, generic medicine manufacturers
usually compete in government or hospital tenders to sell generic medicines.

84

Antimicrobial Resistance Benchmark 2021

Stewardship – sales practices

Which companies are decoupling financial incentives from sales volumes?
Teva, Aurobindo and Shionogi go the furthest towards ensuring that sales agents’financial incentives are not tied to sales volume, either by not promoting theirproducts or by fully decoupling such incentives. Johnson & Johnson, Otsuka andViatris do not promote their tuberculosis medicines, with the exception of Johnson& Johnson, which promotes its multidrug-resistant TB medicine bedaquiline(Sirturo®) in at least one country.
Abbott, Aurobindo, Sanofi and Viatris have newly taken steps in this area. A rangeof strategies are being implemented, for example pilots for full decoupling, or no
promotion in some countries and/or for some products. However, the true impactof these pilots remains unknown. Further progress is still needed toward full decoupling, or towards a policy of no promotion to healthcare professionals globally.
Progress on sales practices has proven to be inconsistent throughout theBenchmark iterations as GSK regressed in this area in the 2020 Benchmark, but thegroup of companies as a whole has progressed as more generic medicine manufacturers are starting to get more involved in this area.

TABLE 9. Overview of sales practices, broken down by company and by coverage of products
and geographies
This table shows which measures each company is taking – or not taking – to decouple financial
incentives from sales volume for their sales staff.

No promotion

Full decoupling of sales

to healthcare

incentives from sales

Partial decoupling of sales incentives fromprofessionals

volumessales volumes

size*

Portfolio% of pay decoupled
Products Geographies Products Geographies Level of sales targets

from volumes● National ● Smaller group ● Individual● Applies to all ● Applies to some ○ Applies to none

● Unknown ● Confidential

Large research-based pharmaceutical companies
Pfizer

112

○

○

●

●

●

●

Novartis

109

○

○

○

○

●

72%

Sanofi

40

●

●

○

○

●

●

GSK

34

○

○

○

○

●

75%

MSD

15

○

○

●

●

●

●

Johnson & Johnson

9

●

●

○

○

●

●

Shionogi

9

○

○

●

●

N/A

N/A

Otsuka

1

●

●

N/A

N/A

N/A

N/A

Generic medicine manufacturers
Teva

143

●

●

N/A

N/A

N/A

N/A

Abbott

87

○

○

●

●

●

●

Viatris

87

●

●

○

○

●

●

Cipla

69

○

○

○

○

●

>99%

Alkem**

52

○

○

○

○

●

●

Fresenius Kabi

52

○

○

○

○

●

●

Sun Pharma**

52

○

○

○

○

●

●

Hainan Hailing**

43

○

○

○

○

●

●

Aurobindo

37

●

●

N/A

N/A

N/A

N/A

Shionogi has been
consistent in its
approach to sales
practices since 2017.
Teva has the largest
portfolio size of any
company in scope, andhas been consistentsince the 2020 Benchmark in its policy of
not deploying sales
agents for the sales of
its antibacterial andantifungal medicines
globally.

Abbott ran a pilot in
2021 where it fully
decoupled incentives
for sales agents fromsales volumes of ananti-infective in India
for three months.
Viatris does not deploy
any sales agents topromote pretomanidor flucytosine to HCPs.

Aurobindo does not deploy sales
agents for the sales of its antibacterial and antifungal medicines
globally.
* Antibacterial and/or antifungal
medicines.

** Alkem, Sun Pharma and Hainan Hailing
do not disclose their sales practices.

85

Stewardship – sales practices

Antimicrobial Resistance Benchmark 2021

Reimbursement schemes could help companies make progress
There are gaps in standards on advertising, marketing and sales of antimicrobials,
but there are also new approaches being used which could lead to improvements.7
These include the use of reimbursement schemes, which aim to remove the component of sales volumes entirely.
As part of pilot schemes ongoing in the UK and Sweden,8 promising new antibacterial medicines that are about to reach the market are selected, and the schemes
ensure that reimbursement by the government is not related to the volume of medicines sold or used. This aligns with stewardship practices, as new antibacterial
medicines should be used sparingly and only as a last resort to avoid the emergenceof resistance against the newest antibacterial medicines on the market.
These new reimbursement schemes provide an opportunity for pharmaceuticalcompanies to completely break the link between sales volumes and financial incentives, while still retaining an appropriate revenue. Going forward, this could be anespecially helpful model to apply to low- and middle-income countries.

86Antimicrobial Resistance Benchmark 2021

STEWARDSH I P – CO I M ITIGATIO N

Conflict of interest comprehensively
mitigated in education programmes forhealthcare professionals

Pharmaceutical companies know how their medicines can be used, responsibly andappropriately, to treat different infections. Many pharma companies contribute toeducational activities for healthcare professionals (HCPs) on how best to manage
the risk of resistance while using their products; but if they do so, they must proactively avoid the risks of conflicts of interest (COI) which are inherent in this area.
Looking at a maximum of five programmes per company, the Benchmark
assesses whether and how companies engage in educational activities aimed at
HCPs, and whether they mitigate COI as part of those programmes.
In 2020, the Benchmark reported that the majority of programmes evaluated
had comprehensive measures in place to mitigate the risk of COI in their educational programmes targeting HCPs. In 2021, there is further progress, as all programmes have at least some COI mitigation in place and there is an increase in thenumber of programmes with comprehensive COI mitigation. The maximum of fiveprogrammes per company which are included in this analysis demonstrate a highexemplary standard of COI mitigation; companies must further ensure that thisstandard applies to all of their programmes.
As in 2020, programmes are most likely to be developed in-house and thus
supported by one or more of the three COI mitigation strategies defined by the
Benchmark. The most common strategy is a pledge not to give any financial andmaterial incentives to participants in the programme.

FIGURE 66. Levels of COI mitigation among the educational

FIGURE 67. How many companies report that

programmes assessed by the Benchmark

they are involved with HCP education?

The Benchmark assessed 57 educational programmes across the companies

This figure shows which companies are involvedin scope. This figure shows how comprehensive the COI mitigation is, andin AMR-related education for HCPs.

also highlights which companies are involved in the programmes which do
not have comprehensive COI mitigation in place.

Programmesthat havesome COI
mitigation
Companies
with some COI
mitigation for
one or moreprogrammes:
AbbottFresenius Kabi
GSK
MSD

Programmes thathave comprehensive
COI mitigation

4
57
programmes
53

There are no programmesthat have no COI
mitigation

3
Companies involvedin educational programmes for HCPs:
AbbottAurobindo
Cipla
Fresenius Kabi
GSK
Johnson & Johnson
MSD
Novartis
OtsukaPfizer
SanofiShionogi
Sun Pharma
Viatris14

Companies not
involved in educational programmesfor HCPs:
Alkem
Hainan Hailing
Teva

87

Stewardship – COI mitigation

Antimicrobial Resistance Benchmark 2021

How companies can mitigate conflict of interest in
educational programmes for healthcare professionals
No incentives to participants: A company pledges that it will

FIGURE 68. The number of educational programmes using different

not provide financial and material incentives to those who

COI mitigation strategies

participate in educational programmes.

All 57 programmes in scope are covered by at least one COI mitigation
strategy. This figure shows how many programmes use the different

Independence of content development: The exclusion of a

types of mitigation strategies, defined on the left.

company’s marketing department in content development

No incentives to participants

and speaker selection.

33

Independence of content development31

No branded materials

No branded materials: The content of an educational pro-

30

Unrestricted grant

gramme excludes branded products or materials.

24

Independent review (e.g. accreditation) 00

Unrestricted grant: Companies can provide unrestrictedgrants to independent third parties. These can be used for

10

20

30

40

An independent review,for example by seeking
and gaining accreditation,is the most robust mitigation against COI. However, no programmes were
found to have this measure in place in 2021.

AMR-related educational activities, without any involvementof the company and without any obligation to include marketing aspects in the programme.
Independent review: An independent review is the mostrobust way for companies to show they mitigate COI withinprogrammes. An independent body such as the Accreditation
Council for Continuing Medical Education (ACCME) can evaluate how COI is mitigated if the provider is a company, and canaccredit educational programmes.

TABLE 10. Which COI mitigation strategies are used in HCP educational programmes?
This figure shows which COI mitigation strategies are used by companies for their HCP educational
programmes, broken down by whether they are delivered by an independent third party or in-house.

Third party
Number of
programmes*

Unrestricted
grant

In-house
Independent Independenceof content
review /accreditation development

No incentives toparticipants

No brandedmaterials

Abbott

5

●

○

●

●

●

Cipla

5

○

○

●

●

●

Fresenius Kabi

5

○

○

●

●

●

GSK

5

○

○

●

●

●

Johnson & Johnson

5

●

○

○

○

○

MSD

5

●

○

●

●

●

Novartis

5

●

○

●

●

●

Pfizer

5

●

○

○

○

○

Shionogi

5

●

○

●

●

●

Sun Pharma

5

●

○

○

○

○

Viatris

5

●

○

●

●

●

Aurobindo

1

○

○

●

●

●

Otsuka

1

○

○

●

●

●

Sanofi

1

○

○

●

●

●

● Applies to all programmes

Alkem**

0

●

●

●

●

●

● Applies to some programmes

Hainan Hailing**

0

●

●

●

●

●

○ Applies to no programme

Teva**

0

●

●

●

●

●

● Not applicable* Up to five programmes in total are evaluated for each company.

** If the company is not involved in AMRrelated educational programmes forhealthcare professionals, there is no conflict of interest mitigation to be assessed.

88Antimicrobial Resistance Benchmark 2021

STEWARDSH I P – AD H E RE NCE

Companies support appropriate use throughbrochure and packaging adaptations
The risk of resistance is lowered when patients understand the risks and adhere
to their courses of treatment until they are completed. When patients are prescribed medicines, the packaging as well as materials such as informational brochures can help them to understand AMR, and how they can minimise these risks tothemselves and their communities. Pharmaceutical companies can adapt packaging
materials to ensure information is clear, for example by presenting it in a local language, or by supporting it by pictograms in areas with low levels of literacy.
Eleven companies out of 17 report taking steps to minimise AMR and facilitate appropriate use through brochure and packaging adaptations. Since the last
Benchmark, Abbott and Aurobindo now report making adaptations.
FIGURE 69. Which types of adaptations do companies use?
This graph shows how many times each different type of brochure or packaging adaptation is reported as being used by any of the companies in scope,for any of their products in scope.
Language needs

10

Adherence facilitation

9

Paediatric use
Literacy levels

52

Environmental conditions 1
0

5

10

Issues that can prevent appropriate use

Examples of how companies adapt their product brochures or packaging to help improveby patients

appropriate use

Language needs

Eight companies have made language adaptations

Patients may not be able to read the• Cipla adapted its patient education leaflets for itraconazole, oxiconazole and fosfomycin trometamol in

included instructions on how to use theproduct appropriately if they are notwritten in the local language.

India. These leaflets contain QR codes that redirect to information in eight to ten regional languages inIndia: Assamese, Bengali, Gujarati, Kannada, Malayalam, Marathi, Odia, Punjabi, Tamil, and Telugu.
• Teva’s packaging for azithromycin and linezolid contains information that is translated into English, Spanish,French and Portuguese. The multilingual packaging was adapted for the receiving country.

Adherence facilitation

Six companies have made adaptations to facilitate adherence

Patients may not be aware they need to• Cipla created leaflets for itraconazole and amorolfine that contain information about things to be con-finish the full course of treatment evensidered while taking antifungal medication, e.g. to complete the course of treatment even if symptoms

if they start feeling better.

improve earlier.
• Johnson & Johnson packaged a six-month treatment regimen (188 tablets) of bedaquiline (Sirturo®) in asingle bottle. This was designed to enable patients to follow a full course of treatment without needing to
make multiple visits to a pharmacy or clinic.

Paediatric use

Five companies have made adaptations for paediatric use

For paediatric patients there may be dif-

• Abbott adapts packaging of eight antibacterial paediatric suspensions by including a QR code on the pack-ferent requirements for the administration or dosing of the product.

aging that directs to a video explaining how to use them appropriately.
• Pfizer has adapted packaging of azithromycin (Zithromax®) as an oral suspension to include a QR code that
directs patients to a video explaining how to administer the oral suspension properly for adults and children. This is applied in Vietnam and the Philippines and the video is played in the local language.

Literacy levels

Two companies have made literacy-related adaptations

For illiterate patients it is difficult to• Abbott adapts packaging for antibacterial medicines in India by including pictograms to illustrate the rec-understand written instructions on howommended usage regimen.

to use the product appropriately.
Environmental conditions

One company has made an environmental adaptation

Local environmental conditions can• GSK designed blister packaging for amoxicillin/clavulanic acid (Augmentin™) with a specific lidding foil that

decrease the effectiveness of theis sensitive to moisture ingress for high humidity environments. This technology also received the Alufoil

product.

Trophy Award for its innovation in technical packaging.

89

Stewardship – adherence

Antimicrobial Resistance Benchmark 2021

More than half of companies support patient education on the risks of AMR
Ten companies are involved in general patient education on AMR through awareness campaigns, brochures, posters, articles, videos, games, comic booklets and a
TV drama series.

TABLE 11. How do companies help patients understand the risks of AMR?

Company

Name of initiative

Description of initiative

Novartis

Mejor Cuidado, Más

Novartis created an educational and emotional-

Saludly-driven multichannel campaign targeted at par-Examples of initiativeents of children: “Better Care More Health” or“Mejor Cuidado, Más Salud”. This campaign includes
an extensive outreach (including a website, videos,email campaign, presentation, brochures and posters) during World Antibiotic Awareness Week in
November.
Johnson & Johnson

MTV Nishedh Live (TVJohnson & Johnson funds the MTV Staying Alive

drama series)

Foundation, which created a TV drama series that
includes a storyline about young people with TB to
help inform them about the signs and symptomsof the disease and to help reduce the social stigma
often faced by patients.

SanofiAnTRIbiotics;

Sanofi educates patients through the AnTRIbiotics

Bact’ Attack;campaign with Cyclamed (in France), a game appli-

Antibio-Responsable

cation called Bact’ Attack, a comic booklet on adherence to tuberculosis treatment (in South Africa) anda website (in French) about the responsible use ofantibiotics.

90

Antimicrobial Resistance Benchmark 2021

STEWARDSH I P

Looking ahead
Antimicrobial stewardship has been a casualty of the COVID-19 pandemic as stewardship programmes were disrupted by changes in healthcare delivery, consequently leading to the over-prescription of broad-spectrum antimicrobials for
COVID-19 patients – despite low evidence of bacterial/fungal co-infection.9,10 While
this highlights the scale of the challenge in antimicrobial stewardship, there areclear ways in which different stakeholders can help tackle the problem.
CO M PAN I ESG OVE R N M E NTS AN D PRO CU R E RS

• Set up surveillance systems, identify gaps in AMR surveilAMR surveillance

lance data, and set up guidelines to harmonise the different• Engage in AMR surveillance programmes to track anti-

types of surveillance data.

microbial resistance, either by setting up programmes• Continue setting up reimbursement schemes for new anti-

in-house or by funding external programmes run by institu-

bacterial and antifungal medicines in which reimbursement

tions such as research organisations.

is not related to the volume of medicines sold. This can help

• Publicly share raw data from these programmes in a readily
accessible manner.

remove the financial incentive linked to sales volume forpharmaceutical sales agents, while retaining an appropriate
revenue for the companies.

Sales practices• Fully and consistently decouple incentives for sales agentsfrom sales volumes, either by avoiding the use of sales• Enforce responsible promotional practices, for example
regarding ethical codes and financial or material incentives
for healthcare professionals.

agents altogether for antibacterial and antifungal medi-• Educate healthcare professionals on the risks of AMR andcines, or by removing the financial incentive linked to sales

new treatment guidelines. This is a responsibility for gov-

volumes of these medicines.

ernments, not pharmaceutical companies, so if healthcare
professionals are already fully up-to-date on AMR educa-

COI mitigation in education programmes

tion then there is no need for companies to get involved in• Ensure a robust conflict of interest (COI) mitigation strat-

this area.

egy when the company is engaged in educational stewardship activities directed at healthcare professionals.
• Adopt the most effective strategies by either funding an

AC AD E M IA / R ES E ARCH

• Pave the path for governments, public health authorities,

independent third party to develop programmes, or seeking

healthcare professionals and other researchers to utilise

accreditation for in-house programmes.

raw data from AMR surveillance. For example, this can beused to forecast disease trends; plan medicine purchases;

Adherence

make better-informed treatment choices; improve policy• Adapt brochures and packaging of antibacterial and anti-

directives and investment decisions for laboratory capac-

fungal medicines to facilitate appropriate use by patients.

ity, infection prevention and control response; and identify• Consider the needs of the patient population, such as local
languages, literacy levels and paediatric use.

newly emerging pathogens.
• Share knowledge of AMR and up-to-date treatment guidelines and recommendations for healthcare professionals

I NVE STO RS• Consider whether companies are taking stewardship intothat are independent from educational activities from pharmaceutical companies.

account for their antibacterial and antifungal medicines.

• Perform studies about systematic medicine use in order• Specifically focus on companies’ engagement in responsible

to create a baseline, identify key problems for corrective

promotional and sales practices and AMR surveillance.

action, and measure follow-up.
• Evaluate the impact of AMR education for healthcare professionals and further optimise the practices, policies, andprogrammes to improve prescribing behaviour and/or to
set up the appropriate facilities and structures to support.

91

Stewardship

Antimicrobial Resistance Benchmark 2021

RE FE RE NCES
1. Van Boeckel TP, Gandra S, Ashok A,
et al. Global antibiotic consumption
2000 to 2010: an analysis of national
pharmaceutical sales data. Lancet
Infect Dis. 2014;14(8). doi:10.1016/
S1473-3099(14)70780-7
2. World Health Organization. Global
Antimicrobial Resistance and Use
Surveillance System (GLASS) Report.;
2014.
3. World Health Organization. National
Action Plan of the Islamic Republicof Iran for Combating Antimicrobial
Resistance(IRIAMR) 2016 - 2021.; 2016.
https://www.who.int/publications/m/
item/iran-national-action-plan-of-the-islamic-republic-of-iran-for-combating-antimicrobial-resistance. Accessed August
31, 2021.
4. Africa CWJ, Abrantes PM dos S.
Candida antifungal drug resistance in
sub-Saharan African populations: A systematic review. F1000Research. 2017;5.
doi:10.12688/f1000research.10327.1
5. Centers for Disease Control andPrevention. Biggest Threats and Data.;
2019. https://www.cdc.gov/drugresistance/biggest-threats.html. Accessed
August 5, 2021.
6. The Expert Panel on the Potential
Socio-Economic Impacts of Antimicrobial
Resistance in Canada. When Antibiotics
Fail.; 2019. https://cca-reports.ca/reports/
the-potential-socio-economic-impacts-of-antimicrobial-resistance-in-canada/. Accessed September 1, 2021.
7. Van der Heijden M. Strengthening theregulation of antimicrobial use to mitigate drug resistance. Global Antibiotic
Research and Development Partnership(GARDP). https://revive.gardp.org/
strengthening-the-regulation-of-antimicrobial-use-to-mitigate-drug-resistance/.
Published July 16, 2021. Accessed August
31, 2021.
8. Gotham D, Moja L, van der Heijden M,
Paulin S, Smith I, Beyer P. Reimbursement
models to tackle market failures for antimicrobials: Approaches taken in France,
Germany, Sweden, the United Kingdom,
and the United States. Health Policy(New York). 2021;125(3). doi:10.1016/j.
healthpol.2020.11.015
9. Lynch C, Mahida N, Gray J.
Antimicrobial stewardship: a COVID
casualty? J Hosp Infect. 2020;106(3):401403. doi:10.1016/j.jhin.2020.10.002
10. Rawson TM, Moore LSP, Zhu N, etal. Bacterial and Fungal Coinfectionin Individuals with Coronavirus: A
Rapid Review to Support COVID-19
Antimicrobial Prescribing. Clin Infect Dis.
2020;71(9):2459-2468. doi:10.1093/cid/
ciaa53092

Antimicrobial Resistance Benchmark 2021

2021
Antimicrobial
Resistance Benchmark
Best Practices

93

Antimicrobial Resistance Benchmark 2021
RESEARCH AND DEVELOPMENT: BEST PRACTICE 1

GSK maintains lead in antibacterial and antifungal R&D to target
priority pathogens
GSK
Topic: Size of R&D pipeline targeting priority pathogens
What: GSK has the largest R&D pipeline of projects targeting
pathogens in scope across all companies
Region: Global
As antimicrobial resistance spreads, new medicines and vac-

is a pathogen that experts warn could become resistant tocines that target priority bacterial and fungal pathogens are

all currently available antibiotics. The company also has anneeded urgently. Infectious diseases projects are risky for

anti-tuberculosis agent considered a new chemical class, withcompanies due to the scientific challenges of discovering new

a new target, new mode of action and no known cross-resist-antibiotics, the complexities of development and the limited

ance to other antibacterial classes.

economic attractiveness of the market.
The Benchmark expects large research-based pharma-

Reflecting its commitment to prevent infections and reduce

ceutical companies to continue engaging and investing insociety’s dependence on antibiotics, GSK dedicates more

R&D that targets priority bacterial and fungal pathogens.

than half of its R&D pipeline to vaccine projects. Of the six

Especially urgent is the need to develop products that offer

companies active in vaccine R&D, GSK reports by far the mosta better chance of lasting effectiveness by operating in novel

projects (16), 13 of which are innovative and three that areways. To determine how ‘novel’ a medicine or vaccine is, theadaptive. Both GSK and Pfizer (with the second highest num-

Benchmark uses four criteria defined by the World Healthber of vaccine projects) have candidates in clinical develop-

Organization (these are: new chemical class; new target; newment to prevent C. difficile, one of the most common causesmode of action; and/or absence of cross-resistance).

of hospital-acquired infections, with an increasing incidence
worldwide.

Why does GSK lead in R&D?
Of the eight large research-based pharmaceutical compa-

N E X T STE PS

nies evaluated, GSK invests the largest absolute amount inSince 2018, the Benchmark has recognised GSK as being

R&D. It leads in R&D targeting the priority bacteria and fungiat the forefront of antimicrobial R&D. The company sup-in scope, with a total of 31 projects in the pipeline (up fromports the AMR Action Fund along with six other compa-

27 in 2020), more than half (19) are in discovery and pre-nies assessed by the Benchmark (Johnson & Johnson, MSD,

clinical stages. Of all companies in scope, GSK’s pipeline isNovartis, Pfizer, Shionogi and Teva), and it collaborates

the biggest, addresses more pathogens designated as ‘criti-

on a diverse range of projects with partners and funders

cal’ and/or ‘urgent’ threats (by the WHO and/or US Centers

including the Combating Antibiotic Resistant Bacteria

for Disease Control) than others, has the most vaccines pro-

Biopharmaceutical Accelerator (CARB-X), the Bill & Melinda

jects, and is developing the largest number of innovative

Gates Medical Research Institute, the TB Alliance, Wellcome

treatments. By investing in innovation and with a high propor-

Trust and the National Institutes of Health (NIH).

tion of projects at an earlier (riskier) stage, GSK shows bestpractice.

In the last 20 years, investment in innovation for antibacterial
medicines and vaccines has declined. The Benchmark expects

Six of eight companies in scope for the R&D Research Area

all large research-based pharmaceutical companies to con-are developing candidates that target pathogens in the ‘criti-

tinue to engage and invest in R&D to combat the spread ofcal’ and/or ‘urgent’ threat categories, including 18 that are in

AMR, whether through private funding or by joining consortia

clinical-stage development or are recently approved products.

with public funding, and/or through discovery programmes,

GSK has the most of these projects, followed by Pfizer andin-licensing or acquisitions. Companies must find new ways

Shionogi. Since 2020, these companies have increased their

to develop and commercialise novel products that can remain

number of ‘critical’ and/or ‘urgent’ priority pathogen projects.

effective, and ensure they reach the populations that needthem.

GSK is developing gepotidacin, a late-stage candidate that is
considered a new chemical class, with a new mechanism ofaction, which targets E. coli and N. gonorrhoeae. The latter94

Antimicrobial Resistance Benchmark 2021
RESEARCH AND DEVELOPMENT: BEST PRACTICE 2

Pfizer makes strategic investment in antibacterial and antifungal
R&D to get new products to market
PFIZER
Topic: R&D pipeline targeting priority pathogens
What: Pfizer has developed a diverse strategy to maintain andevolve its engagement in R&D, and actively seeks new opportunities to expand and enrich its involvement
Region: Global
New medicines and vaccines are needed urgently to target

B Streptococcus and respiratory syncytial virus. Its vaccine forpriority pathogens. However, it can be risky to invest in devel-

S. pneumoniae was recently approved by the FDA. Its C. diffi-

oping antibacterial and antifungal products. Large companies

cile vaccine is in Phase III trials, ahead of GSK’s own C. difficile

that possess greater capacity, scientific expertise, equipment

candidate.

and regulatory know-how can play a valuable role when theychoose to invest in smaller companies, and/or acquire prom-

N E X T STE PS

ising innovations. This can help to take forward products at a

The Benchmark expects large research-based pharmaceu-

greater speed.

tical companies to continue engaging and investing in R&D
that targets priority bacterial and fungal pathogens, whether

What does best practice look like?

in-house or through collaborations. Pfizer engages with AMR

Pfizer works internally and externally to maintain and growfrom a range of angles and liaises with diverse stakehold-its engagement with AMR, focusing both on treatment and on

ers and local networks in low- and middle-income countries.

the prevention of infections caused by difficult-to-treat resist-

In R&D, its approach is highly strategic: it identifies promising

ant pathogens. In contrast with GSK, a high proportion of its

candidates for investment and supports smaller innovators

R&D projects (eight of 13) are in late-stage clinical develop-

to move products forward to market. Other companies canment (Phase II and onwards).

emulate this proactive, strategic approach and their ongoing

Pfizer’s diverse strategy includes acquiring innovation fromcommitment to AMR.

others, supporting smaller biotech companies, and increasing
its in-house pipeline. It engages across all sectors to support
R&D and works with a range of private and public partners
and funders including the US government (BARDA), AbbVie
and the Bill & Melinda Gates Foundation. It also supports the
AMR Action Fund, pledging USD 100 million over 10 years.
By putting its weight behind innovative, early-stage R&D,
the company is helping to bring promising novel products tomarket. Strategic acquisitions such as Arixa Pharmaceuticals
and Amplyx Pharmaceuticals have helped grow Pfizer’s pipeline of projects from eight to 13 and broaden the numberof pathogens targeted. Through Amplyx, Pfizer moved into
antifungal R&D and is now developing a clinical-stage antifungal medicine candidate (fosmanogepix) to treat invasive fungal infections caused by Candida spp. among others.
Through Arixa’s lead compound ARX-1796, Pfizer aims to create next-generation oral antibiotics, targeting gram-negative
pathogens that cause resistant urinary tract and other infections. In late 2019, Pfizer also invested in ContraFect, which
is taking forward Phase III trials of its candidate exebacase,a first-in-class direct lytic agent targeting S. aureus, to help
patients with highly resistant infections.
Pfizer’s vaccine development programme is second in size
only to GSK’s and has products to help protect against Group95

Antimicrobial Resistance Benchmark 2021
RESEARCH AND DEVELOPMENT: BEST PRACTICE 3

Otsuka and Pfizer set consistent standard for stewardship andaccess plans
OTSUKA, PFIZER, GSK, SHIONOGI, SANOFI

cal development, in partnership with the Bill & Melinda Gates

Topic: Stewardship and access planning during late-stage

Foundation, and aligns its access and stewardship plans with

developmentthat foundation’s global access requirements.

What: Comprehensive plans for late-stage projects, with a

Pfizer does not enforce its patents in Least Developed

variety of strategies tailored to the product being developed

Countries (from May 2020). It has comprehensive accessRegion: Global

and stewardship plans for most candidates, including one in
Phase III (aztreonam/avibactam) to treat serious gram-neg-

Antimicrobial resistance poses opposing challenges: accessative bacterial infections in adults, for which it plans a global

and excess. Millions of people live without reliable access to

pre-registration compassionate use programme. It also has

effective antibacterial and antifungal products, yet excessive

robust, multifaceted plans for its vaccines to prevent C. dif-or inappropriate use of these products can render them inef-

ficile (for which no vaccine is yet on the market) and Groupfective. The need to enhance access goes hand in hand with

B Streptococcus (which causes around 90,000 infant deaths

that of ensuring appropriate use to keep medicines working.

annually, co-funded by the Bill & Melinda Gates Foundation).

When companies plan for these challenges during R&D,
they take account of public health needs and can ensure more

GSK, Shionogi and Sanofi: examples of good practicerapid access to new medicines and vaccines at more afforda-

GSK deploys company-wide policies to ensure access andble prices following their entry to markets. Companies are

stewardship plans are in place for its five late-stage projects,

expected to have plans in place for pipeline projects in Phasebut it does not tailor plans to specific products as much as

II and beyond. The Benchmark assesses the extent to which

Pfizer and Otsuka do for theirs. Shionogi has progressed bycompanies create and disclose plans to make new products

actively seeking out partners to improve access and steward-

swiftly accessible upon market entry, and to ensure they areship to its antibiotic candidate (cefiderocol).

used appropriately thereafter. For medicines, plans for accessmust be coupled with plans for stewardship.
Specifically, the Benchmark looks at the late-stage anti-

Sanofi has developed Shan6™ vaccine specifically for children in low- and middle-income countries. Shan6™ wasapproved in May 2021 in India. There, Sanofi has a dedicatedbacterial and antifungal R&D projects targeting priority path-manufacturing facility where it applies supply-chain best

ogens for which companies have plans in place for access (inpractices including buffer and safety stocks. Additional coun-

countries in scope and where burden of disease is higher) andtries in scope for registration include Thailand and Kenya. For

for stewardship on a global basis.

Shan6™, Sanofi applied for WHO prequalification to ensure
access to the vaccine in all countries eligible for support from

Otsuka and Pfizer leadGavi, the Vaccine Alliance. Pooled demand through UNICEF

All but two of 20 medicine projects in late-stage clinicaland Gavi tenders ensures quality of supply and affordability.

development (from all companies in scope) have in place both

In addition, Sanofi has developed equitable pricing strategies,

an access and stewardship plan. Otsuka and Pfizer stand out,

conducted a payer pricing survey in nine countries, and takes

both reporting comprehensive access and stewardship plansaccount of affordability by market type.

for all late-stage projects in their pipelines. Access strategies
include WHO prequalification, managed access programmes,

N E X T STE PS

equitable pricing, provisions for sustainable manufactur-

When pharmaceutical companies work with funders suching and supply, registration, responsible IP and licensing andas Wellcome Trust, the Bill & Melinda Gates Foundation orother provisions, some stipulated in partner agreements with

CARB-X, provisions attached to funding may require them toorganisations such as the Combating Antibiotic Resistant

put in place strong access and stewardship plans. Some com-

Bacteria Biopharmaceutical Accelerator (CARB-X) and the Bill

panies go the extra mile and develop their own plans inter-& Melinda Gates Foundation.

nally. Pfizer leads the field, matching the quality of its inter-

Otsuka has plans for two late-stage candidates, both tocombat tuberculosis. For its version of delamanid to treat chil-nally developed plans with that of those it develops for
co-funded projects.

dren with drug-resistant TB, it works with the Pediatric Drug
Resistant-TB Initiative launched by the Stop TB Partnership’s
Global Drug Facility (GDF), national TB programmes andother stakeholders to ensure global access; it plans to complete a technology transfer shortly after receiving the firststringent regulatory authority approval of this child-friendly
formulation. Otsuka is developing its second candidate(OPC-167832), a highly innovative agent in Phase II of clini-

96

Antimicrobial Resistance Benchmark 2021
RESPONSIBLE MANUFACTURING: BEST PRACTICE 1

Shionogi is first to publish the details of its antibacterial wastemanagement performance
SHIONOGI

also names its only external private waste-treatment plant,

Topic: Disclosure of environmental risk-management

used for disposal by incineration, in scope.

What: Shionogi is the first company to report publicly on how

Shionogi belongs to the AMR Industry Alliance, which pub-it manages the environmental risk of its antibacterial waste,lishes recommended discharge limits, and it makes AMR cen-

disclosing detailed information

tral to its contribution to global sustainability. By self-regu-

Region: Japan and India

lating and sharing information proactively (so far, only 33%
of its supplier sites fully comply with guidance), the company

During pharmaceutical manufacturing, antibacterial residue issets a precedent for transparency. It demonstrates best prac-released into the environment through factory wastewaters.

tice by providing details specific to products, sites, and suppli-

The environment, composed of water and soil, naturally con-ers, which allows third parties to assess product-specific risks

tains bacteria, but when exposed to antibacterial waste thaton an ongoing basis. Shionogi reveals whether sites discharge

is released by the manufacturing sites, this can trigger the

beneath safe levels, discloses results clearly and supports eth-emergence and/or selection of resistance genes and contrib-

ical procurement.

ute to AMR development.
Currently there are no specific regulations governing dis-

GSK and Novartis are the only other companies to publicly disclose some information on compliance, though a lackcharge of antibacterial waste, so it is important for compa-

of detail makes it hard to assess which of their sites and prod-

nies to disclose publicly how they manage this. As stakehold-ucts might pose a risk for AMR. GSK discloses that all 20

ers, such as governments, academic experts and procurers,of its own sites and 32 of 45 supplier sites comply with dis-depend on self-reporting, this increases companies’ responsi-

charge limits. Novartis reports that 80% of its own sites com-bility to be transparent. When companies publish details andply with pharmaceutical limits, though the company’s data isoutcomes of strategies to manage the environmental risks

not specific to antibacterials.

associated with discharge, independent third parties can analyse processes and performance, and assess progress for

N E X T STE PS

keeping emissions at safe levels. The publication of methods

Shionogi says it will consider making publicly available theand data also allows procurers a path to ensure they can lev-

details of how it performs mass balance calculations to showerage responsible environmental practices of company’s man-the quantities of product discharged during production. It

ufacturing in its sustainable procurement policies.

also commits to disclosing to the Benchmark actual details of

Of the 17 companies in scope, only three provide someaudit results. To progress further, it could name other supplierinformation publicly about which sites comply with guidance

locations on a city level to increase understanding of its sup-on safe levels. The extent to which manufacturing practices

ply chain and associated AMR risks.

of other companies pose a risk for AMR is not yet clear.

Other companies should follow Shionogi’s lead and takesteps to disclose locations of suppliers, how many sites have

Why does Shionogi stand out?

safe levels of discharge, and compliance on a per-productAs the first company to publish extensive detail, Shionogi

basis. Since AMR-related risk also arises downstream, theleads the field. In 2020 it published an environmental report

Benchmark looks for companies to disclose details of external

disclosing information on audit results covering wastewater

wastewater treatment plants, helping to ensure use of appro-

management, solid-waste management and discharge limits.

priate technologies and protocols can minimise the spread ofIts disclosure covers all antibacterial APIs and/or drug prod-

resistance.

ucts the company makes at its site in Kanegasaki, Japan, andthose made at nine supplier sites. Information is presented
clearly and concisely, is broadly accessible and includes a tableof antibacterials, as well as their connection to Shionogi sites
and suppliers, and compliance with discharge limits.
At its own site, Shionogi complies with limits for all APIs
and all five of its drug products. It names the locations offive out of nine supplier sites (four in Japan, one in India) andthe products they supply. These quantify their discharge levels, and three of them (making flomoxef, doripenem and sulfamethoxazole/trimethoprim) comply with limits. Shionogi
97Antimicrobial Resistance Benchmark 2021
APPROPRIATE ACCESS: BEST PRACTICE 1

Pfizer and Viatris use registration to expand availability of
on-patent antibiotics in low- and middle-income countries
PFIZER AND VIATRIS

treatment-intolerant/non-responsive MDR-TB). Significantly,

Topic: Registration of on-patent antibiotics

Viatris filed rapidly (within 12 months of receiving its first

What: Pfizer and Viatris have each expanded registration of

approval) in India, which has one of the highest burdens ofspecific on-patent medicines in more than 15 low- and mid-tuberculosis.

dle-income countries since the last Benchmark.
Region: 102 low-and middle-income “access” countries

N E X T STE PS

Especially in the case of key antibiotics, the Benchmark
Antibacterial and antifungal medicines and vaccines are

expects companies to improve access through registration.

essential for treating and preventing infectious diseases. Yet

Filing can help companies increase patient reach and cut inap-

millions of people live without reliable access to them or lack

propriate use of antibiotics. Market size, financial opportu-

information to use them properly. When companies do notnities and unclear local regulatory requirements may pre-file to register new and on-patent medicines in countries invent companies from filing a product for registration in aneed, low availability can also increase the risk of resistance.

specific country: in response, certain initiatives (such as thePatients may purchase or be prescribed medicines that do

WHO Collaborative Registration Procedure and The African

not meet medical need or quality standards.

Medicines Regulatory Harmonization programme) can pro-

Registration is an important step to ensure products arevide companies with support for product registration. Having

made available for sale, especially in countries with higher lev-

local or regional offices in low- and middle-income countries

els of disease and inequality. Companies can show a commit-

may facilitate companies in submitting registration dossiers.

ment to enter markets in need by filing for registration with

Pfizer, which demonstrates best practice, intends tolocal regulatory authorities as widely and rapidly as possible

expand access further in additional countries. It could con-after a product is first approved.

sider filing for registration in countries with high burdens of
intra-abdominal infections, complicated infections of the uri-

Which companies demonstrate best practice?

nary tract or lower respiratory tract infections. Viatris could

Pfizer and Viatris are the only companies to have expanded

expand registration of pretomanid by filing for registration inregistration to on-patent antibiotics, submitting filings inmore access countries, in particular the countries with a highadditional low-and middle-income countries for specific prod-

burden of MDR-TB identified by the WHO, where it has com-

ucts. Since the last Benchmark, Pfizer has filed its reserve

mercialisation rights.

antibiotic ceftazidime/avibactam (Zavicefta™) in 18 further

Few online regulatory databases yet track the registration

countries including three low-income countries (Ethiopia,

of medicines in smaller, lower income countries. While regu-

Tanzania, and Uganda). When implementing its access strat-

latory agencies in low-and middle-income countries may lackegy for antimicrobials, Pfizer takes account of factors relat-

the capacity for building and updating such databases, com-

ing to patient and provider needs, and the ability for prod-

panies can play a role by increasing transparency about whereucts to be used in consistency with its stewardship principles.

they file products for registration. For example, Johnson &The antibiotic, approved in 2016, plays a key role in treating

Johnson is the only company in scope to publicly disclosecomplicated intra-abdominal infections and hospital-acquired

where it filed its MDR-TB medicine (bedaquiline). Companies

pneumonia, which can both be fatal. Zavicefta™ is now reg-should keep expanding registration to the most countries andistered in a total of 20 of the 102 low- and middle-income

make commitments for future action.

countries in the Benchmark assessment, including Brazil andIndia.
Viatris newly filed its anti-tuberculosis medicine pretomanid (Dovprela) for registration in 23 access countries
including five low-income countries (Democratic Republicof Congo, Ethiopia, Mozambique, Tajikistan and Zimbabwe).
Almost all countries where Viatris registered pretomanid
since 2020 have tuberculosis burdens that the WHO judges
to be among the world’s highest. The medicine was developed by the TB Alliance and was first approved by the FDA in
2019. It is used for difficult-to-treat tuberculosis (XDR-TB and98

Antimicrobial Resistance Benchmark 2021
APPROPRIATE ACCESS: BEST PRACTICE 2

Viatris leads in strategies to expand access to TB treatment(pretomanid)
VIATRISclear, well-described and detailed access strategies – stating

Topic: Expanding access to on-patent antibacterial medicines

patient and geographic reach, considering ability to pay, andWhat: Viatris uses a variety of strategies to improve theindicating price level – meet the criteria for gold standard.

affordability of its anti-TB medicines among underserved pop-

The company also makes commitments for future access.

ulations in countries in scope, and expand access.

As well as its partnership with GDF-Stop TB, Viatris part-

Region: 102 low-and middle-income countries (“accessners with other stakeholders including the KNCV in Ukraine,

countries”)

where the BPal regimen was introduced in 2020. Additionnal
programmes are planned in Tajikistan, Myanmar, Vietnam,

According to WHO, tuberculosis (TB) deaths increased in

the Philippines and Indonesia. Another strategy is donations:2020 for the first time in more than a decade, rising to 1.5 mil-the company provided 400 cumulative treatment courses oflion. The situation is expected to worsen in 2021. Currently,

pretomanid, shared between the Indian National Tuberculosis

4,100 people die from TB daily. Between 2018 and 2020

Elimination Program and the South African Conditional

across all adult age groups, only half of those with TB wereAccess Program. To ease local healthcare budget constraints,

treated, and just 41% percent of children.

it also agreed to donate 50 courses each to Uzbekistan andMore broadly, people need appropriate access to new andKyrgyzstan for research programmes.

on-patent antibacterial medicines. Lack of availability and/or

A third initiative is a named patient access programme.

supply may lead patients to take medicines that do not meet

Such programmes are not sustainable in the long-term but

medical need or quality standards, increasing the risk of AMR.

do take account of affordability to help ensure fast access to

In resource-limited countries with high burdens of diseases

new medicines in low- and middle-income countries, acting as

such as TB, challenges around appropriate access to products

a shortcut to innovative and needed medicines. Viatris under-

remain significantly higher. To expand access, companies cantakes to offer pretomanid to up to 40 eligible patients perplan and implement a range of strategies to address productyear in every country where it is not registered or available forregistration, accessibility, affordability and supply chains.

free (or on par with GDF access pricing). Low- and lower-middle-income countries will be offered a price on par with GDF’s

What does best practice look like?
Viatris has expanded access to its TB medicines. The com-and Viatris will expand the programme if demand increases.
Otsuka has a voluntary licensing agreement with Viatris topany, formed in 2020 from the merger of Mylan andaccelerate access to delamanid in high TB-burden countries.

Upjohn, combines a variety of strategies to increase access.

These two companies have entered into a technology transfer

Pretomanid (Dovprela) is a relatively new medicine, devel-agreement allowing Viatris to produce a low-cost generic ver-oped by the TB Alliance and first approved by the FDA insion of delamanid in India. The delamanid produced by Viatris

2019. It is part of the BPal (bedaquiline, pretomanid and line-

does not currently meet quality assurance requirements aszolid) regimen to treat patients with extensively drug-resist-it is not approved by a Stringent Regulatory Authority or the

ant TB (XDR-TB) and treatment-intolerant/non-responsive

WHO Prequalification Programme.

MDR-TB. Viatris partners with the GDF-Stop TB Partnershipto provide pretomanid at a defined global access price to150 countries and territories, including all 102 low- and mid-

N E X T STE PS

Companies should consider the full range of access strat-

dle-income countries in scope of the Benchmark. A six-monthegies from the toolkit to determine what is most appro-

course of treatment costs USD 364 (USD 2 per tablet). Viatris

priate, such as voluntary licensing, partnering with exter-

also distributes a generic version of delamanid (Deltyba™,

nal stakeholders, patient assistance programmes, and equi-produced by Viatris under licence from Otsuka) to treat

table pricing policies. Companies should also take affordabil-

MDR-TB.

ity into account, ensuring that their medicines and vaccines
are affordable to the most people, including in the poorest

Why does Viatris stand out?

countries.

Viatris stands out in its proactive approach to reach more
people with its TB medicines in more countries, including
those with the highest TB burdens. By using and combining
a range of strategies, Viatris shows willingness and commitment to provide access to its TB medicines. The company’s

99Antimicrobial Resistance Benchmark 2021
APPROPRIATE ACCESS: BEST PRACTICE 3

Tech transfers and support for local manufacturing hubs toincrease local availability of medicines and vaccines
AUROBINDO, GSK, NOVARTIS, OTSUKA, PFIZER,

of its vaccine, facilitate transfer of technology and reduce

SANOFI, VIATRIS

manufacturing risks.

Topic: The creation of local hubs to manufacture antibiotics
What: Seven companies are involved in technology transfers

Otsuka is working with Viatris (previously Mylan) toand other initiatives to enable antibacterial and antifungals

transfer technology to produce and distribute delamanid(Deltyba®). The first phase included initial manufacture, pack-medicines and vaccines to be produced locally.

age and distribution of delamanid in access countries. FromRegion: 8 countries (Brazil, China, India, Nigeria, Pakistan,2021, full API manufacturing will enable the generic version ofSouth Africa, Vietnam, Zambia).

delamanid to be made available in access countries includingSouth Africa and India and to be procured through the Global

When supply chains are fragile or demand increases unex-

Drug Facility following WHO-prequalification.

pectedly, this can lead to shortages in medicines and vaccines.

In Nigeria, Sanofi has worked since 2008 to produce med-

Since these products can be produced through sensitive, multi-stage and highly technical processes, multiple manufactur-

icines locally, including the antibiotic metronidazole (Flagyl®).
It helps local plants meet quality standards and upgrade

ers need to master these processes to ensure that supply cancapabilities.

meet demand, and to minimise the impacts of shutdowns.

In Brazil, GSK partners with three state-owned vaccine

Shorter supply chains can reduce the risk of fragmentation

manufacturers to produce priority vaccines, including anti-

and stockouts and enable people to access a wider range ofbacterial vaccines. It is transferring manufacturing practices

products.

such as formulation and packaging, technical know-how, andAntibiotic production can be hampered by low profitability

analytical testing methods. GSK aims to upgrade infrastruc-and low sales volumes. Companies that make these medicines

ture, develop local capabilities, and train employees in goodshould also aim to supply them continuously in low-and-mid-

manufacturing practices. Through this, Brazil will be enabled

dle income countries, where people lack access to affordable,

to produce at least 60 million vaccine doses annually for its

quality-assured products. This involves creating transparency

population.

around supply chains for antibacterial and antifungal medi-

Novartis partners with third parties in Pakistan to trans-cines and vaccines and working toward improving local manu-

fer manufacturing knowledge and produce products locally,

facturing capabilities and working with multiple API suppliers.

including its Sandoz penicillin portfolio. As the developmentof effective new antibacterial medicines is failing to keep pace

What does best practice look like?

with resistance, older medicines such as penicillin have a role

To support the development of local manufacturing in low-

to play.

and middle-income countries, companies are investing in

Aurobindo’s manufacturing facilities are located in India. It

building capacity and sharing skills, knowledge, technologies,

supplies APIs to low- and middle-income countries and aims

and manufacturing methods with local manufacturing part-to improve their capacity to produce finished medicines.

ners. Initiatives need to be sustainable, enabling more countries and regions to produce their own medicines and vac-

N E X T STE PS

cines locally over the long term. Ten companies report that

Companies need to develop local manufacturing sites andthey are supporting local manufacturing (such as by carrying

share knowledge, especially in resource-poor regions without technology transfers) in at least one of the 102 low- andhigh demand such as sub-Saharan Africa. The Benchmark

middle-income countries in scope.

looks for companies to build capacity and/or transfer tech-

Africa accounts for nearly 17% of the world’s population,

nologies to cover more products and enable countries tobut produces only 3% of the medicines and 1% of the vaccines

become more self-sufficient and distribute their own med-

it consumes. Seven companies report technology transfers toicines. Companies are expected to make commitments for

African countries to produce antibiotics or antifungals medi-

future action and to include transfers of technology in theircines or vaccines locally.

strategy and reporting.

Pfizer is working with the South African government andLack of capability and training are significant challenges.

Biovac Consortium Cape Town to produce its pneumococcal vaccine (Prevnar13®) locally, taking raw materials throughCompanies that demonstrate best practice often partner withto the release of fully packaged products. It has developed

stakeholders (such as governments and NGOs) to plan trans-

automative processes to standardise the complex formulation

fers of technology to enable products to be made sustainably.

others and/or open offices locally. They also work with other100

Antimicrobial Resistance Benchmark 2021
STEWARDSHIP: BEST PRACTICE 1

Shionogi continues to fully decouple sales agents’ bonuses fromsales volumes of antibacterial medicines
SHIONOGIN E X T STE PS

Topic: Mitigating the risk of overselling

To improve further, Shionogi could choose to cease alto-

What: Shionogi is steadfast in fully decoupling its financial

gether the promotion of its products to healthcare profes-

rewards for sales agents from the volume of antibacterial andsionals. Companies such as Abbott, Pfizer and MSD, which

antifungal medicines they sell, in order to mitigate the risk ofhave run decoupling pilot projects, can expand this practiceoversellingto more countries and products. Incentives for sales agents

Region: Global

can be awarded at individual, smaller group or national level.
When incentives are awarded at national and smaller group

One of the main drivers for the emergence of antimicrobial(rather than individual) level, they are linked less directly toresistance (AMR) is the inappropriate use of antibacterial andtotal pay, so that when an individual agent sells a higher vol-antifungal medicines. When companies rely on making highume of products, this does not directly increase that person’svolumes of sales, their resulting sales practices can lead tototal pay. All companies can follow Shionogi’s lead and fully

the promotion of overuse and misuse. Steps need to be taken

decouple incentives on a global basis, and maintain this prac-

to ensure products are used only when needed.

tice to minimise the spread of resistance.

By avoiding the use of sales agents altogether for antibacterials and antifungals, companies can reduce their risk ofoverselling to healthcare professionals and the prescription of
unneeded medicines. Companies that do retain a sales force
can decouple incentives for their agents from sales volumes,
so that bonuses do not depend on how much product is sold.
Why does Shionogi lead?
Shionogi was the first large research-based pharmaceuticalcompany to fully decouple its incentives for sales agents fromsales volumes. It began in Japan in 2016 and extended thepractice globally the following year. The Benchmark recognised this as best practice in 2020.
The company does not link the payment of bonuses to thevolumes its sales agents sell. It incentivises agents instead
through linking to competencies such as interactions withhealthcare professionals and knowledge of AMR. No othercompany in scope has fully decoupled such incentives for
its agents globally. Just as importantly, Shionogi applies thispractice globally for all products in scope, and is consistent inmaintaining the practice.
Cipla, the first generic medicine manufacturer to fully
decouple its incentives for agents globally, was recognisedfor best practice in 2020. It now links <1% of its incentives tosales volumes. GSK pioneered the practice in 2013 but now
no longer fully decouples. Other companies decouple incentives only for some products and/or in selected regions. Only
Shionogi applies the practice across the board.

101

Antimicrobial Resistance Benchmark 2021
STEWARDSHIP: BEST PRACTICE 2

No sales teams for anti-tuberculosis medicines, to shrink the risk ofoverselling

VIATRIS, OTSUKA, JOHNSON & JOHNSONN E X T STE PS

Topic: Mitigating the risk of overselling

It is especially important that strong stewardship meas-

What: Viatris, Otsuka and Johnson & Johnson have stopped

ures are used for new medicines to help patients who do nottheir use of sales agents to promote their tuberculosis med-

respond to other treatment. Promotion can lead to over-icines to healthcare professionals in order to minimise theselling and weaken treatment effectiveness. The decision to

spread of resistance

not promote these medicines is a significant step in the right

Region: Global

direction.

When antimicrobial products are used too much or wrongly,

fungal medicines to healthcare professionals. In the case of

they can become ineffective and drive AMR. Companies that

last-resort antibiotics (such as those the WHO classifies asrely on making high volumes of sales may deploy sales prac-“reserve”), the Benchmark urges manufacturers to avoid pro-tices that lead to overselling and promote inappropriate use.

motion to mitigate overselling, misuse and the spread of

When companies choose not to promote their products, they

resistance.

Many companies still promote their antibacterial and anti-

can mitigate this risk and help to limit resistance.
Given the wide spread of multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB), it is
crucial that new medicines do not become ineffective. These
are medicines of last resort, and global health and national
public health bodies recommend they be made available onlyin specialised centres under tightly controlled conditions.
What does best practice look like?
Otsuka, Johnson & Johnson and Viatris have chosen not topromote their on-patent tuberculosis medicines (respectively delamanid/Deltyba®, bedaquiline/Sirturo® and pretomanid/Doprevla) in most countries, despite having received
marketing authorisation. Johnson & Johnson does promote
bedaquiline (Sirturo®) in at least one country. These are theonly three on-patent medicines for the disease: the first two
are used to treat MDR-TB, while the newer Dovprela (first
approved in 2019) treats XDR-TB, non-responsive MDR-TB
and treatment-intolerant TB.
By choosing not to promote, these three companies
remove the risk of incentivising sales agents to oversell tohealthcare professionals. In 2020, the Benchmark recognised Otsuka and Johnson & Johnson for best practice: both
remain consistent in their approach.

102

Antimicrobial Resistance Benchmark 2021
STEWARDSHIP: BEST PRACTICE 3

GSK adapts Augmentin™ packaging to suit a range of patient needs
and support its responsible use
GSK

N E X T STE PS

Topic: Improving the appropriate use of antibacterial medi-

No standards yet exist for the development and use of adap-

cine by adapting packaging and brochures

tations, but GSK demonstrates that it is possible to combine a

What: GSK has adapted the way it presents amoxicillin/clavu-

range for optimal effectiveness. The Benchmark expects com-lanic acid (Augmentin™) to help patients use the product inpanies to be proactive and creative, and take steps to help

appropriate ways

patients use their medicines well. It looks for common-sense

Region: 44 countries

adaptations for all products where appropriate, and for commitment to future action.

One of the main drivers for the emergence of resistance isthe misuse of antibacterial and antifungal medicines. Whenpatients do not complete a full course of treatment, for example, this can contribute to the conditions that make medicines
ineffective.
Medicines prescribed or bought over the counter are more
likely to be used appropriately if they come with high-quality
information. Companies can adapt their brochures and packaging to help patients with this. Brochures might be written
in local dialects, or pictograms may be used if illiteracy is an
issue for the population.
How does GSK demonstrate best practice?
Two-thirds of the companies in scope (11 of 17) make at least
one adaptation. Very few make changes to consider multiple patient needs: Abbott and Pfizer have three, and threecompanies report two. GSK is the only company to take fullaccount of the range of differing patient needs.
GSK takes account of a range of identified needs toensure it helps patients to use amoxicillin/clavulanic acid
(Augmentin™) appropriately. GSK has considered language,
ability to adhere to a regimen, environmental conditions, levels of literacy and paediatric use. No other company in scope
has adapted its brochures and/or packaging in accordancewith this range of needs.
Augmentin™ is a widely used antibiotic, a type of penicillin that treats bacterial infections. For Mauritius, Angola andMozambique, GSK has translated its patient knowledge card
into French and Portuguese: this card also highlights information to help patients continue the course of the medicine asprescribed. For patients in Pakistan, a high-humidity environment, GSK has created a bespoke blister packaging with a lidding foil sensitive to moisture. In Gulf Cooperation Council
regions with low levels of literacy, GSK deploys an AI-enabled
chatbot that uses graphics in a smartphone application toeducate patients. The company also offers oral suspensions
and flavoured dosing syringes across 35 countries to help children take the medicine.

103Antimicrobial Resistance Benchmark 2021
STEWARDSHIP: BEST PRACTICE 4

Pfizer remains only company to sharing raw data on AMR
surveillance, adding countries and pathogens
PFIZER
Topic: AMR surveillance

N E X T STE PS

What: Pfizer has expanded its AMR surveillance programme

The Benchmark looks for all companies involved in AMR

to include more priority pathogens and more countries, andsurveillance to make a commitment to share their raw data incontinues to share its raw data publicly to increase stake-an easily accessible way, such as through the AMR Register.

holder insight

Pfizer, which already leads, could continue to expand its

Region: 81 countries (global)

programme to cover surveillance of resistance in further
countries.

Data on AMR surveillance helps governments, public healthNo company except Pfizer yet reaches the gold standard.

authorities and healthcare professionals measure andOther companies share aggregated results through open-ac-

respond to infections, analyse local trends and prioritisecess data platforms and/or in open-access journals. Johnson

objectives in stewardship policies. Companies involved in sur-& Johnson shares raw data from clinical trials through aveillance to monitor resistance of pathogens against antibac-

mechanism that involves requesting access, which is moreterial and/or antifungal medicines need to share their raw

restrictive. GSK and Shionogi both report they intend to pub-data publicly, so experts, researchers and healthcare pro-

licly share raw data but have not done so yet, while MSD

fessionals can use it. Access can help stakeholders to fore-

intends to also share data through a mechanism that involves

cast disease trends; plan medicine purchases; make better-in-

requesting access.

formed treatment choices; and improve policy directives andSharing raw data enables public health bodies and profes-

investment decisions for laboratory capacity, infection pre-sionals to use it in a range of valuable ways. Raw data can bevention and control response, and identification of newly

used for studies on the burden of AMR, including the IHME

emerging pathogens.

Global Burden of Disease study on AMR morbidity or mortal-

Through its Antimicrobial Testing Leadership andity (the GRAM project). It can provide valuable insights into

Surveillance (ATLAS) programme, which began in 2004,

where resistance to medicines occurs, and may help predict

Pfizer works with UK-based curator Micron Research to mon-which medicines will be ineffective because of resistance,

itor pathogen resistance against the antibacterial products it

facilitating better treatment choices.

markets and is developing. ATLAS monitors changes in antibiotic susceptibility, bacterial resistance trends and emergenceof new resistance strains. Around 48,000 bacterial isolates
are collected each year and Pfizer updates the database every
six months.
How does Pfizer lead?
Pfizer was the first company in scope to share raw data fromATLAS (from 2018) on the AMR Register, an open-accessdata platform set up by Open Data Institute and Wellcome
Trust. In 2020, the Benchmark recognised this as best practice. Data can be downloaded from the site, while aggregateddata is made available via the ATLAS website to anyone who
registers with an email address.
Since 2020, through the ATLAS website, Pfizer has chosen
to share new aggregated data on antifungal resistance. It has
also expanded its programme to include new priority pathogens and countries, with a focus on Africa. Of all AMR surveillance programmes operated by companies in scope, Pfizer’s
covers the most priority pathogens (13), up from nine in 2020.
A collaboration with the governments of Ghana, Malawi,
Kenya and Uganda (Surveillance Partnership to Improve Data
for Action on Antimicrobial Resistance, or SPIDAAR) has seen
it expand its programme to 81 countries (from 73 in 2020).
104

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

Company Report Cards

The 2021 Antimicrobial Resistance Benchmark includes a set of 17 company report cards, providing a detailed overview of each company’s performance. Companies are all different in the way they operate, where
they operate, and in their portfolio of investigational and marketed
products.
The Report Cards are divided into six sections:
Performance
Explains the company’s performance in the 2021 Benchmark, including
the drivers behind any movement, and the main areas where it scores
well or poorly compared to its peers.
Opportunities
Sets out tailored opportunities for the company to do more to ensure
access and address AMR, taking account of its R&D pipeline (whereapplicable), product portfolio, and othrer factors.
Changes since 2020
Highlights the most notable changes in the company’s performancesince the 2020 Benchmark, including a selection of new or expanded
activities and programmes.
Sales and operations
Summarises the company’s global operations, revenue per product andregion, including mergers and acquisitions relevant to antibacterial andantifungal products.
Pipeline and portfolio
General description of the company’s operations, recent mergers &acquisitions, revenue per region, and geographical reach.
Performance by Research Area
Details the company’s performance in each of the three areas measured
by the Benchmark: R&D, Responsible Manufacturing, and Appropriate
Access and Stewardship.

105

Antimicrobial Resistance Benchmark 2021

GSK

Overall Performance
2020

2021

86% 84%▼

Access to Medicine Foundation

GlaxoSmithKline plc
Large R&D-based pharmaceutical company
Stock exchange: LSE • Ticker: GSK • HQ: Brentford, UK • Employees: 94,066

GSK
PERFORMANCEGSK is the leader among the large research-based pharmaceutical

Performance in the Benchmark

0%companies in scope and performs well in its evaluated Research Areas.
R&D: With 31 R&D projects, about half of them vaccines, GSK leads in
R&D. Eleven of its projects target critical and/or urgent pathogens. Twoof its medicine candidates in clinical development are novel. GSK reports
access and/or stewardship planning for all five of its late-stage projects.
Responsible Manufacturing: Performs strongly. Reports comprehensive
environmental risk-management strategy for own sites and suppliers;

Appropriate Access: Performs strongly. Files some of its on- and off-

on-patent antibacterial vaccines in access countries.
Stewardship: Performs well. It partly decouples incentives for sales
agents from sales volumes. It publicly shares aggregated results of its
SOAR surveillance programme. It reports broad conflict of interest
mitigation for its educational programmes. It adapts brochures and100%

Points93%

R&D

28/ 3087%

Manufacturing

13/ 1580%

Access20/ 2575%

Stewardship0%

15/ 2050%

100%

How GSK was evaluatedpatent products for registration in access countries. Reports several
strategies to expand access and ensure continuous supply to its

50%

/ 90
76/

Performance by Research Area

co-leads in reporting compliance with limits at own sites and suppliers;
publicly discloses this compliance.

Points84%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

packaging for patients.
● ● ● Scored●

Not scored

OPPORTUNITIES FOR GSKCHANGES SINCE 2020

Expand and tailor access and stewardship plans for critical late-stage R&D projects. As a leader in• In February 2020, GSK joined the Project toantibacterial and antifungal R&D with the largest pipeline, GSK can further strengthen their compa-

Accelerate New Treatments for Tuberculosis

ny-wide policies and project-specific plans to ensure new medicines are swiftly available to those in(PAN-TB), a collaboration among philan-

critical need but also to prevent excessive use. GSK maintains policies and plans for their late-stage

thropic, non-profit and sector partners thatR&D projects and can make plans more wide-reaching and timely. As an example, for its vaccine

aims to develop an investigational drug regi-

Bexsero®, that is in phase III targeting N. gonorrhaeae, GSK can define the access countries where
it plans to file for registration, based on burden of disease and where resistance for N. gonorrhaeae

men capable of treating all forms of TB.
• Compared to 2020 Benchmark analysis, GSK

is highest and where it considers ability-to-pay in its pricing strategy. In addition, GSK can expand its

tracks the compliance of its own and suppliers’

stewardship plans for its medicine R&D projects through more comprehensive surveillance activi-

sites with discharge limits. All of GSK’s own

ties by covering more priority pathogens and countries, as well as re-evaluating its sales practices

sites and 95% of its suppliers’ sites are report-

for when these medicines reach the market to safeguard them from overuse and misuse.
Increase public disclosure on environmental risk management. GSK publishes information on

edly compliant with discharge limits.
• Since 2020, GSK has publicly shared infor-

some of the components of its environmental risk-management strategy including compliance per-mation on compliance percentages of own

centages of its own and suppliers’ sites with discharge limits. While it reports 100% complianceand suppliers’ sites, specific to antibacterial

at its own sites, it can disclose more information to provide clear evidence of its progress pub-production.

licly. Disclosure of information, including the results of audits and antibacterial discharge levels of• GSK received funding from CARB-X, up to

its own sites and suppliers’ sites, is important. It can also publicly disclose the names and locations

USD 18 mn, to support the development ofof its suppliers and waste-treatment plants for increased transparency. GSK can also apply limits

two unique vaccine projects that target thedirectly in effluent to fully mitigate AMR risk.

prevention of group A streptococcus (Strep A)

Comprehensively mitigate COI for educational programmes. GSK organises medical education

infections and infections caused by Salmonella

programmes for healthcare professionals on responsible use of antimicrobial medicines. It ensuresenterica which cause invasive nontyphoidalthat branded materials are not used in most educational programmes. It can ensure that this issalmonellosis (iNTS) disease and typhoidapplied in all educational programmes.

fever. Currently there are no vaccines available

Fully decouple incentives for sales agents from sales volumes. GSK links part of its sales agents’against these infections.

incentives to sales volumes of antibacterial and antifungal medicines. It can fully decouple incentives for sales agents from sales volumes again.
Publicly share raw data from surveillance programme. GSK runs the multinational Survey ofAntibiotic Resistance (SOAR) programme, which is focused on community-acquired respiratory-tract infections. It can publicly share raw data from this surveillance programme, following through on clear commitments to share this with the University of Washington (as part of the
GRAM project) and on the AMR Register.

106

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

GSK
Turnover by business segment

Therapeutic areas: Respiratory, HIV, Immuno-inflammation, Oncology

2019

Business segments: Pharmaceuticals, Consumer healthcare, Vaccines

2020

Product categories: Innovative medicines, Vaccines, Consumer health

17,554
17,0560

products

10,000

Pharmaceuticals

M&A since 2020: In July 2019, GSK and Pfizer combined their consumer
health care business in a new joint venture, with GSK having the majority and controlling an equity interest of 68%. In February 2021, GSK signed

7,157

8,995

6,982

10,03320,00030,000Consumer
Consumer
Healthcare
Healthcare

Vaccines

40,00050,000mn GBP

40,00050,000mn GBP

GSK
Turnover by region

an agreement to sell the cephalosporin antibiotic business to Sandoz

201913,8908,069(Novartis division) for USD 350 mn in addition to milestone payments up to2020

14,5568,164

USD 150 mn.

010,000

United States

11,795
11,37920,000Europe30,000International

PIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 31 projects targeting pathogens in scope* (15 antibacterialMid-sized portfolio: At least 51 products: 28 antibacterial medicines; 19

medicines; 15 antibacterial vaccines; 1 antifungal vaccine)

antibacterial vaccines; 4 antifungal medicines

Development stages: 10 clinical projects, 5 in Phase I, 2 in Phase II and 3 inOn-patent vaccines: 8 (Infanrix® IPV Hib, Infanrix® Hexa, Boostrix®,

Phase III, including a Phase III project for an expanded indication of its sero-

Infanrix® Hib, Boostrix® Polio, Menveo®, Bexsero®, Synflorix®)group B meningococcal vaccine (Bexsero®) for the prevention of gonor-

Off-patent/generic medicines: 9 of 43 were selected for analysis* (amox-rhoea; and 19 discovery/preclinical projects.

icillin [A], amoxicillin/clavulanic acid [A], cefadroxil [W], cefuroxime [W],Novelty: 2 novel projects, GSK-3036656, for the treatment ofclotrimazole [F], colistin [R], dapsone [T], griseofulvin [F], polymixin B [R])Myobacterium tuberculosis, that meets all four WHO innovativeness

AWaRe medicines**: 8 Access group; 9 Watch group; 2 Reserve group

criteria; and gepotidacin, for the treatment of infections caused by

Anti-TB medicines**: 1Enterobacteriaceae and Neisseria gonorrhoeae, and which belongs to a
new chemical class and has a new mode of action.

GSK
Pipeline for priority pathogens‘Critical’ and/or ‘urgent’ pathogens: 11 projects, with the focus on carbapenem-resistant Escherichia coli and drug-resistant N. gonorrhoeae. GSK has
one vaccine against C. difficile in Phase I of clinical development.
Regulatory approvals: 0 approvals for products targeting pathogens in
scope.

15
0

10

15 1
20

30

40

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

GSK
Products on the market
19
0

20

28 4
40

60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Largest amount invested in R&D

lute R&D investment figure compared to thetargeting bacterial and fungal pathogens. Out

GSK reports to the Benchmark the amountother companies who reported investments toof the 31 projects, ten are in clinical develop-

invested during 2019 and 2020 in R&D for anti-

the Benchmark. GSK is a contributor to the AMR

ment, 19 are in discovery/preclinical stage andbacterial and antifungal medicines and/or vac-

Action Fund.

2 projects are in technical lifecycle. GSK did notcines for pathogens in scope. Specific invest-

obtain marketing approval for any of its products

ment figures were provided under confidential-

A.2.1 GSK has the largest R&D pipeline among

ity. GSK reports above average R&D investments

the large R&D-based companies

relative to its revenues among the compa-

The company reports 31 projects targeting path-nies assessed. GSK reports the largest abso-

ogens in scope: 15 medicines and 16 vaccines,

during the period of analysis.

Pipeline targeting priority pathogens: 31*** As at 24 September 2021
Discovery

Pre-clinical

Phase I

Phase II

Phase IIIIMI ENABLE or Shigella♦ Enteric fever (bi-valent
conjugate) vaccine [S.
enterica (typhi & paratyphi A)]♦ Invasive non-typhoidal
Salmonella (iNTS; bi-valent GMMA) vaccine [S.
enterica serovars typhimurium + enteritidis]♦ Shigella spp. (multivalent GMMA-based)vaccine♦ Invasive non-typhoidal
Salmonella (iNTS; bi-valent GMMA) vaccine [S.
enterica serovar Typhimurium + Enteritidis &conjugate for S. enterica
serovar Typhi)]♦ Group A Streptococcus(4-valent recombinantconjugated adjuvanted)
vaccine♦ C. difficile vaccine(GSK2904545A)

GSK-070 (GSK3036656) [M. tuberculosis]

Gepotidacin [E. coli]* See Appendix V for information about eligibility for R&D projects andAppendix VII for eligibility
criteria of products.
** Listed on the 2019
WHO EML.

♦ Staphylococcus aureus
vaccine (GSK3878858A)
FimH (GSK3882347)[E. coli]♦ M. tuberculosis prophylactic vaccine [GSK692342/
SB692342; M72/AS01E]

Approval

Gepotidacin - additional
indication [N. gonorrhoeae]♦ N. gonorrhoeae vaccine (Bexsero®) - additional indication of serogroup B meningococcal
vaccine♦ Vaccine
GMMA = Generalized modules for membrane antigens*** Includes 17 projects not shown in the ﬁgure: 15 projects provided to the Benchmark on the basis of conﬁdentiality and 2 projects in technical lifecycle (heat-stable and cold-stable formulations of GSK’s Streptococcus
pneumoniae (Synflorix®) vaccine).

107

Antimicrobial Resistance Benchmark 2021

A.2.2 Pipeline with highest number of innova-

Access to Medicine Foundation

jects. GSK’s vaccines in clinical stages of devel-ing pathogens in scope. It reports having pro-opment include candidates targeting C. difficile,ject-specific access plans for most of these pro-

GSK’s clinical-stage medicine pipeline con-

S. aureus and N. gonorrhoeae. Moreover, GSK isjects. All five projects have ongoing trials insists of both innovative and adaptive R&D pro-developing M72/AS01E in collaboration with theaccess countries.†

jects. GSK has four innovative medicine anti-Bill & Melinda Gates Medical Research Institute,bacterial candidates in clinical development,a Phase II tuberculosis vaccine candidate.

tive candidates

making the company’s clinical pipeline the one
with the highest number of innovative candi-

GSK reports that it has developed an equitable pricing strategy framework for low- and middle-income countries (LMICs) that applies acrossA.2.4 Largest number of projects targetingits portfolio and business units. Its access plans

dates among all companies evaluated in the‘critical’ and/or ‘urgent’ pathogens

include equitable pricing strategies, registra-

Benchmark. This includes GSK-3036656, for

GSK has 11 projects targeting pathogens definedtion filings, non-exclusive licensing and supply

the treatment of tuberculosis, which meets allas ‘critical’ by WHO’s list of priority pathogens

chain commitments. GSK states that it does notfour WHO’s innovativeness criteria; and gepoti-

and/or characterised as ‘urgent’ threats by thefile patents in Least Developed or Low-Income

dacin, for the treatment of infections caused by

US Centers for Disease Control and Prevention

countries nor does it enforce historic patents.

Enterobacteriaceae and N. gonorrhoeae, which(CDC). In clinical development, GSK has medi-

GSK does not conduct clinical trials in countries

belongs to a new chemical class and has a newcine candidates against Carbapenem-resistant/where it does not intend to pursue registration

mode of action. GSK also has a non-traditional

ESBL-resistant E. coli and N. gonorrhoeae; andand to make the product available for use. GSK

medicine in clinical development.

vaccine candidates against C. difficile and N.

commits to conducting global surveillance stud-gonorrhoeae.

ies for its new antibacterials to enable appropri-

A.2.3 Largest vaccine pipeline

ate use and support stewardship.

GSK reports 16 vaccine projects in its pipeline.

A.3

project-specific plans for access and

It is by far the largest vaccine pipeline of the

stewardshipsix companies active in vaccine development. It
includes 13 innovative and three adaptive pro-Company-wide commitments and

GSK has five late-stage R&D projects target-B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Comprehensive environmental risk-man-pliant with discharge limits.

agement for own sites and suppliers;

GSK expects external private waste-treat-levels themselves are not published. It also
does not publish: (1) the results of environmen-

tracks compliance with limits at own

ment plants to comply with its general envi-

tal audits, conducted at its own sites, the sites

sites and suppliersronmental standards. GSK audits these plantsof suppliers and/or external private and public

GSK reports a comprehensive strategy to mini-at least every 3 years (based on risk) whichwaste-treatment plants; or (2) a list of thesemise the environmental impact of wastewaters

includes checking the suitability of technologies

suppliers and plants.

and solid waste from antibacterial manufactur-

used for processing waste and protocols for pre-ing at its sites, including audits every three years.

venting contamination. It requests external pri-

It reports setting discharge limits in the receiv-

vate and public wastewater treatment plants foring environment for all antibacterials manufac-

dilution and flow rate data to inform the mass

tured at its sites, based on PNECs to limit AMR,

balance approach and employs conservative

GSK reports that its own sites and suppliers

as recommended by the AMR Industry Alliance.

measures when needed.

have a system to maintain high-quality antibac-

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

terial production consistent with international

Discharge levels are quantified at all sites using
Publicly discloses some information on

GMP standards. This includes periodic risk-

cal analysis if applicable. GSK reports that all its

environmental risk management andbased audits and tracking of corrective and pre-20 sites, or 100%, are compliant with discharge

compliance with limits

ventive actions. GSK does not require its suppli-a mass balance approach, verified by chemi-

B.2

GSK publishes some components of its envi-

ers to audit their own suppliers, but do encour-

GSK requires third-party suppliers of anti-ronmental risk-management strategy and is aage them to do so. The Benchmark found nobacterials to follow the same standards, includ-

member of the AMR Industry Alliance. It dis-requests for official corrective action from theing limits based on PNECs. It reports conducting

closes that all its 20 (100%) own sites manufac-

FDA or EMA related to non-conformities withon-site audits every three years. It requests andturing antimicrobials and 32 of 45 (71%) of sup-cGMP at GSK’s own sites or any subsidiaries that

reviews the discharge levels of its suppliers. It

plier sites are compliant with discharge targets

manufacture antibacterials.

reports 37 of 39 supplier sites, or 95%, are com-

set by the AMR Industry Alliance.‡ The discharge

limits.

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries†
GSK is not eligible for indicators: C.1.1 and C.2.1.

countries including 19 LICs. Seven of its rele-gate vaccine Synflorix®, filed in 45 access coun-

For more information, see Appendix VII.

vant products are filed in less than 10 accesstries followed by Infanrix® Hexa, its vaccine usedcountries.

to protect against diphtheria, tetanus, pertussis,

C.1.2 Filed to register off-patent/generic medicines in 16 access countries on average
GSK performs above average, filing eight of its

hepatitis B, polio and bacterial meningitis (Hib),
C.1.3 Filed to register on-patent vaccines in 17
access countries on averagenine relevant off-patent/generic medicines for

GSK has an average performance, filing seven ofregistration in 16 access countries on average. Its

its eight relevant on-patent vaccines for regis-

most widely filed relevant product is the antibi-

tration in access countries. Its most widely filed

otic amoxicillin/clavulanic acid filed in 62 accessrelevant vaccine is the pneumococcal conju-† 102 low- and middle-income countries
where better access to medicine is mostneeded.
‡ Discrepancy with compliance data in B.1
is explained by GSK’s submission data

for the Benchmark being more up todate than publicly available data.

filed in 31 access countries. Two of its eight relevant vaccines are filed for registration in at least
one LIC.

108

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

C.2.2 Several strategies to expand access to

on-patent vaccines in scope. It aims to expand

sharing by conducting 3-year forecasts andoff-patent/generic medicines

access to its on-patent vaccines in access coun-

annual long-term demand forecasting (up to

GSK performs above average. It aims to expand

tries through tiered pricing policies

10 years). GSK mitigates against shortage risks

access to its off-patent/generic medicinesand public or private partnerships. GSK partners

by keeping buffer stocks for both APIs and fin-in access countries through donations, sec-with MSF and UNICEF to provide Synflorix® atished products. It ensures dual sourcing for crit-ond-brands, patient support programmes, ten-the lowest price tier during humanitarian situ-

ical APIs. GSK reports three capacity build-ders, and equitable pricing policies. GSK pro-ations. GSK provides evidence of patient reaching or technology transfer initiatives in accessvides evidence of patient reach and geographic

and geographic reach for some of its reported

countries, such as its support to the Strategic

reach for all its reported approaches. For exam-

approaches. For example, it estimates that 56

Training Executives Programme (STEP) in GAVI-

ple, GSK donated more than 200,000 units of its

mn doses of Synflorix® were supplied to Gavi-

eligible countries. To mitigate against substand-branded amoxicillin/clavulanic acid antibiotic in

eligible countries in 2020, through its partner-ard and falsified products, GSK works closely2020 through humanitarian partnerships, includ-

ship with Gavi The Vaccine Alliance.

with local law enforcement, conducts online anding one with Save the Children.

offline investigations or uses security features
C.3

C.2.3 Several strategies to expand access to
on-patent vaccines

Leader in strategies to ensure

such as serialised barcodes and tamper-evident

continuous supply

packaging.

GSK performs above average, with strate-

GSK performs above average, with accessgies reported in all four areas assessed. GSK

strategies reported for all its eight relevant

ensures accurate demand planning and dataC

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Broad COI mitigation strategies in place

trends and/or include treatment guidelines forfor its educational programmes

healthcare professionals. In some countries

GSK performs well in conflict of interest (COI)

these include GSK SOAR surveillance data for

mitigation for the five AMR-related educa-

the antibacterials amoxicillin/clavulanic acid

GSK runs the multinational Survey of Antibiotic

tional programmes for HCPs assessed by the(Augmentin™) and cefuroxime (Zinnat®).

Resistance (SOAR) programme, which is focused

Benchmark. Four programmes have all three

C.7

Active in one AMR surveillance programme; openly publishes aggregatedresults

on community-acquired respiratory-tract infecMakes five types of brochure and/tions in more than 30 countries and has been

Benchmark: (1) content is developed inde-or packaging adaptations to facilitate

running since 2002. GSK only shares the aggre-

pendently from its marketing department; (2) aappropriate use by patients

gated results through peer-reviewed open-ac-

COI mitigation strategies looked for by theC.6

pledge not to provide financial or material incen-

GSK adapts brochures and packaging to facil-cess journal articles. In addition, it will be shar-tives to participants; and (3) it does not use

itate the appropriate use of amoxicillin/clavu-

ing SOAR data with the University of Oxford andbranded materials. The remaining programme

lanic acid (Augmentin™) by patients. GSK is the

University of Washington (as part of the GRAM

has two COI mitigation strategies: in some coun-leader in this measure, taking account of lan-

project) as well as on the AMR Register, antries where these programmes were presentedguage, adherence to treatment, literacy, theopen-access data platform, with these projects

the content could be branded.

environment and paediatric use. For exam-

aiming to complete in Q4 of 2021.

ple, it has translated a Patient Knowledge Card
C.5

Engages in sales and marketing practices

into English, French and Portuguese. This card

to address appropriate use

highlights information to improve adherence

GSK is middle-performing in sales practices. It

to treatment. Moreover, GSK has created blis-

reports that it partly decouples incentives forter packaging with a specific lidding foil that issales agents from sales volumes of its antibacte-sensitive to moisture for high humidity environ-rial and/or antifungal medicines. Its percentage

ments. Further, it has created oral suspensionsof variable pay linked to sales volumes is 25%,

and flavoured dosing syringes for paediatricand this is set at the smaller group level.

patients in 35 countries.

GSK engages in marketing practices that
aim to address the appropriate use of its antibacterial and/or antifungal medicines. Its marketing materials reflect emerging resistance109

Antimicrobial Resistance Benchmark 2021

JNJ

Overall Performance
2020

2021

68% 68%=

Access to Medicine Foundation

Johnson & Johnson
Large R&D-based pharmaceutical company
Stock exchange: NYSE • Ticker: JNJ • HQ: New Brunswick, NJ, USA • Employees: 136,400

JNJ
PERFORMANCE
Johnson & Johnson performs above average overall in its evaluated

Performance in the Benchmark

0%

Research Areas compared to the other large research-based
pharmaceutical companies in scope.
R&D: Johnson & Johnson is a middle-performing company in the
R&D Research Area. Its 14-project pipeline has two vaccines. It has
projects that target critical and/or urgent pathogens. Its two late-stage
development projects are covered by project-specific access plans.
Responsible Manufacturing: Performs strongly. Reports comprehensive

Appropriate Access: Performs well. Files some of its on- and off-patent

50%

80%

12/ 1572%

Access18/ 2580%

Stewardship
0%50%

16/ 20100%

How Johnson & Johnson was evaluated1

2.1 2.2 2.3 2.4

3

●

●

●

A R&D

Stewardship: Performs well. It generally does not promote bedaquiline(Sirturo®) to healthcare professionals. It shares raw data of its DREAM

1

2

3

B Manufacturing ●●●brochures and packaging for patients.

Points15/ 30

Manufacturing

to expand access and ensure continuous supply of its relevant products.

conflict of interest mitigation for its educational programmes. It adapts

100%

50%

R&D

medicines for registration in access countries. Reports some strategies

surveillance programme in a restricted manner. It reports comprehensive

/ 90
61/

Performance by Research Area

environmental risk-management strategy for own sites and suppliers;
quantifies discharge levels at all own sites.

Points68%

Overall score

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

OPPORTUNITIES FOR JOHNSON & JOHNSON

Not scored

CHANGES SINCE 2020
• Johnson & Johnson launched its inaugural

Diversify access plans for late-stage R&D projects. Johnson & Johnson has one medicine and one

satellite center for Global Health Discovery

vaccine in late-stage development. It can improve access to these new products, by developing

hosted at LSHTM focused on addressing theplans for registration, affordability and sustainable supply. For example, for their phase III vaccine,

threat of AMR and TB.

ExPEC9V, Johnson & Johnson can define the access countries where they will file for registration,• In February 2020, Johnson & Johnson joined

based on burden of disease, and where it considers ability-to-pay in its pricing strategy. Johnson &the Project to Accelerate New Treatments forJohnson can also engage with external partners with the expertise to help boost availability of theTuberculosis (PAN-TB), a collaboration among

vaccine in relevant territories once approved.

philanthropic, non-profit and private sec-

Ensure compliance with antibacterial discharge limits at own sites and suppliers by tracking andtors partners that aims to develop an investi-

publicly disclosing progress and results. Johnson & Johnson reports to set limits and to quantify

gational drug regimen capable of treating all

the discharge levels at its own sites and suppliers’ sites. To provide clear evidence of its progress, it
can track compliance at all sites and publicly disclose the results. Disclosure of information, includ-

forms of TB.
• Johnson & Johnson is funder and member ofing the results of audits and antibacterial discharge levels of its own sites and suppliers’ sites, isthe consortium VALUE-Dx. VALUE-Dx is theimportant. It can also publicly disclose the names and locations of its suppliers and waste-treatment

first Innovative Medicines Initiative project ini-plants for increased transparency.

tiated by six in vitro diagnostic companies who

Expand reach of bedaquiline (Sirturo®) for eligible MDR-TB patients. Johnson & Johnson has

work with 20 non-industry partners to combat

continued to reach more patients with MDR-TB through tenders, patient assistance programmes,

AMR and improve patient outcomes.

access price settings and public or private partnerships. It can further apply these mechanisms• Johnson & Johnson received two FDA indi-

to expand access and ensure diagnosed patients are treated, especially in countries where gaps

cation extension approvals for bedaqui-remain between diagnosis of MDR-TB and treatment.

line (Sirturo®)* for MDR-TB in adolescents

Fully decouple incentives for sales agents from sales volumes. Johnson & Johnson does not pro-

(12 - <18years) and pediatrics indications (5mote bedaquiline (Sirturo®) in most countries. Johnson & Johnson can apply the practice of notpromoting this product globally. Further, it can fully decouple incentives for sales agents from sales- <12years).
• In 2020, Johnson & Johnson collaborated

volumes of all antibacterial and antifungal medicines.

with the GDF Stop TB to reduce the price of

Publicly share raw data from surveillance programme. Johnson & Johnson runs the multinational

bedaquiline in eligible low- and middle-income

Drug Resistance Emergence Assessment in MDR-TB (DREAM) programme, which is focused on

countries.

resistance against bedaquiline (Sirturo®). It can publicly share raw data from this surveillance programme, anonymised and in a freely accessible format.

* As part of combination therapy of pulmonary tuberculosis due to multi-drugresistant M. tuberculosis.

110Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONSJNJSales by business segment

Therapeutic areas: Cardiovascular/metabolism/(other), Immunology,

2019

Infectious diseases, Neuroscience, Oncology, Pulmonary hypertension.

2020

Business segments: Consumer health, Medical devices, Pharmaceutical

M&A since 2020: None in the antibacterial and/or antifungal sectors

42,19814,0530

Product categories: Consumer health products, Medical devices, Innovative
medicines, Vaccines

13,89825,96345,57220,000Consumer Health40,00060,000

Pharmaceutical

22,95980,000

Medical Devices

100,000
mn USDJNJ
Sales by region
2019

42,097

2020

43,1330

20,000

United States

39,96239,45140,00060,00080,000International

100,000
mn USDPIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 14 projects targeting pathogens in scope** (12 antibacterial

Comparatively small portfolio: At least 8 products: 3 antibacterial medi-

medicines; 2 antibacterial vaccines).

cines; 5 antifungal medicines

Development stages: 1 clinical project, ExPEC9V (formerly ExPEC10V)

On-patent medicines: 1 bedaquiline (Sirturo®)a Phase III, 9-valent vaccine for the prevention of invasive extraintestinal

Off-patent/generic medicines: 3 of 7 were selected for analysis** (itra-

pathogenic E. coli disease in adults; and 12 discovery/preclinical projects.

conazole [F], levofloxacin [W], miconazole [F])Novelty: 0 novel clinical-stage medicine projects.

AWaRe medicines***: 1 Watch group‘Critical’ and/or ‘urgent’ pathogens: Projects targeting invasive extraintes-

Anti-TB medicines***: 1

tinal pathogenic E. coli (ExPEC) and P. aeruginosa.
Regulatory approvals: 2 approvals. In August 2019, marketing authorisa-

JNJ
Pipeline for priority pathogens

tion by the FDA was granted for the adolescent indication (12 - <18 years)of the MDR-TB drug bedaquiline (Sirturo®)* and in May 2020, for the paediatric indication (ages 5 - < 12 years).

2

12

0

10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

JNJ
Products on the market
3
0

5
10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority** bacteria & fungi

A.1

Investments in R&D

A.2.1 Medium-sized pipeline

A.2.2 No clinical-stage novel medicines

Johnson & Johnson does not disclose pub-The company has 14 projects targeting patho-

Johnson & Johnson’s clinical-stage medicine

licly, or to the Benchmark, its R&D investments

gens in scope: 12 medicines and two vaccines,

pipeline consists of one candidate, the paediat-

during 2019 and 2020 in antibacterial and anti-

all targeting bacterial pathogens. Out of the 14

ric adaptation of bedaquiline (Sirturo®). Johnson

fungal medicines and/or vaccines for pathogens

projects, eight are in discovery stage, four are in& Johnson does not currently have any medi-in scope. Johnson & Johnson has pledged USD

preclinical stage, one is in clinical development

cine candidate that is considered novel in clinical

100 mn to the AMR Action Fund over the next

and one received marketing approval during thedevelopment.

ten years.

period of analysis.

Pipeline targeting priority pathogens: 14† As at 24 September 2021
Discovery

Pre-clinical♦ S. aureus vaccine

Phase I

Phase II

Phase III

Approval♦ Extraintestinal pathogenic E. coli vaccine(ExPEC9V) ‡Bedaquiline (Sirturo®)[M. tuberculosis][FDA/Aug-19]: additional
population: adolescent(12 - <18 years)[FDA/May-20]: additional population: paediatric (5 - <12 years)♦ Vaccine† Includes 11 conﬁdential projects not shown in the ﬁgure.
‡ Progressed to Phase III after the end of the period ofanalysis.

**See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
***Listed on the 2019 WHO EML.

111

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

A.2.3 Two vaccine candidates

and Prevention (CDC). In clinical development,

will extend to the new pediatric approval: for use

Johnson & Johnson reports two vaccine pro-Johnson & Johnson has a vaccine candidate,in patients aged 5 - < 12 years and weighing at

jects in its pipeline. Its clinical-stage candidate,

ExPEC9V, that targets extraintestinal pathogenic

least 15 kg.

ExPEC9V is a Phase III vaccine targeting extrain-

E. coli. Johnson & Johnson also has projects that

testinal pathogenic E. coli. Johnson & Johnson

target P. aeruginosa.

Johnson & Johnson is planning to expand its

also has a vaccine candidate against S. aureus in
preclinical stage.

There are no clinical trials running in accesscountries§ for the EXPEC9V vaccine, but

A.3

Access and stewardship plans for late-Phase III trial to access countries.

stage projects
A.2.4 Candidates targeting critical and/or
urgent priorities

Johnson & Johnson has one vaccine (ExPEC9V)

Johnson & Johnson has projects targeting path-and one medicine in late-stage development[bedaquiline (Sirturo®)]. They are both covered

ogens defined as ‘critical’ by WHO’s list of prior-by project-specific access plans.

ity pathogens and/or characterised as ‘urgent’

The current stewardship activities ongoingthreats by the US Centers for Disease Control

for the adult indication of bedaquiline (Sirturo®)B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Comprehensive environmental risk-man-report how many suppliers have quantified dis-ronmental audits, conducted at its own sites, theagement for own sites and suppliers;

charge levels and are compliant with limits.

sites of suppliers and/or external private andsets limits at own sites and suppliers

Johnson & Johnson expects exter-

public waste-treatment plants; (2) a list of theseJohnson & Johnson reports a comprehen-

nal private waste-treatment plants to comply

suppliers and plants; or (3) the levels of antibac-

sive strategy to minimise the environmental

with its general environmental standards.

terial discharge from its own or suppliers’ sites.

impact of wastewaters and solid waste gen-Johnson & Johnson reports that it audits pri-erated from antibacterial manufacturing at its

vate waste-treatment plants based on risk andsites, including conducting audits every three

region. It also employs conservative measures

years. It reports setting discharge limits in thefor effluents sent to external public wastewater

receiving waters for all antibacterials manufac-

treatment plants.

tured at its sites, based on PNECs to limit AMR,

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

Johnson & Johnson reports that its own
sites and suppliers have a system to main-

Publicly discloses some information on

tain high-quality antibacterial production, con-Johnson & Johnson also reports quantifying dis-environmental risk management

sistent with international GMP standards. Thischarge levels at all its own sites using a mass bal-Johnson & Johnson publishes some compo-

includes periodic risk-based audits and tracking

ance approach, verified by chemical analysis if

nents of its environmental risk-managementof corrective and preventive actions. In general,applicable.

strategy. It is a member of the AMR Industry

Johnson & Johnson also requires its pharmaceu-

Johnson & Johnson requires third-party

Alliance, which publishes a list of recommended

tical suppliers to audit their own supplier sites

suppliers of antibacterial APIs and drug products

antibacterial discharge targets. It discloses thatbased on risk. The Benchmark found no requests

to follow the same standards, including limits

it has completed audits and an environmental

for official corrective action from the FDA orbased on PNECs. It reports conducting on-siterisk assessment of all its pharmaceutical sup-EMA related to non-conformities with cGMP at

audits of its suppliers typically every three years.

pliers located in China and India, which also

Johnson & Johnson’s own sites or any subsidiar-Johnson & Johnson requests and reviews thecovers antibacterial discharge levels. Johnson &ies that manufacture antibacterials.

discharge levels of its suppliers. It does not

Johnson does not publish: (1) the results of envi-

as recommended by the AMR Industry Alliance.

C

B.2

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries§
Johnson & Johnson is not eligible for indica-

filed for registration in at least one LIC.

tors: C.1.3 and C.2.3. For more information, see
Appendix VII.

lative 700,000 patients worldwide by 2025.
Bedaquiline is available in all 30 WHO high-bur-

C.2.1 Several strategies to expand access toden countries for MDR-TB.

its on-patent medicine
C.1.1

Filed to register on-patent medicines in

Johnson & Johnson performs above average.

30 access countries

It aims to expand access to its one relevant

C.2.2 Limited information on strategies toexpand access to off-patent/generic
medicines

Johnson & Johnson performs above average,

on-patent medicine in access countries throughfiling its one relevant on-patent medicine fortenders, patient assistance programmes, accessJohnson & Johnson has an average perfor-

registration in 30 access countries, including

price settings and public or private partner-

mance. It has set equitable tiered-pricing princi-

eight LICs. The medicine is the MDR-TB medi-

ships. It collaborates with the GDF-Stop TB

ples and publicly states to apply equitable pric-cine bedaquiline (Sirturo®). Johnson & Johnson

Partnership to provide 100 mg bedaquiline at

ing policies to its antifungal itraconazole andpublicly discloses on its company’s website

a global access price of USD 340 per 6-month

antibiotic levofloxacin. Johnson & Johnson pro-where bedaquiline was filed for registration.

treatment course to GDF-eligible countries.

vides evidence of patient reach and geographic

The GDF-Stop TB Partnership also provides

reach for two of its three relevant products in

C.1.2 Filed to register off-patent/generic med-

the paediatric formulation of bedaquiline (20scope. Details were provided under the basis of

icines in 29 access countries on averagemg) at a price of USD 200 per 6-month treat-confidentiality.

Johnson & Johnson performs above average,

ment course. Johnson & Johnson provides evi-filing all its three sample off-patent/generic

dence of patient reach and geographic reach for

medicines for registration in 29 access countries

all its reported approaches. It publicly commits

on average. All its three sample products are

to providing its MDR-TB medicine to a cumu-§ 102 low- and middle-income countries

where better access to medicine is mostneeded.

112

Antimicrobial Resistance Benchmark 2021

C.3

Access to Medicine Foundation

Several strategies to ensure continuous

casts and global donor grant budgeting cycles.

Pharmstandard (Russia). It mitigates substand-supplyIt mitigates against shortage risks by keeping a

ard and falsified products by having a dedicatedJohnson & Johnson performs above aver-buffer stock for APIs and finished products. Bothteam. It uses packaging security features andage, with strategies reported in all four areas

bedaquiline API and finished product are manu-

digital technologies to detect illicit trade.

assessed. It ensures accurate demand plan-

factured in India with flexibility to scale produc-ning and data sharing by forecasting demandtion. It reports several capacity building or tech-of bedaquiline (Sirturo®) based on local tender

nology transfer initiatives including a technol-

patterns and utilisation trends in high burden

ogy transfer for the formulation, filling, and pack-

MDR-TB countries, distributor demand fore-

aging processes of bedaquiline including withC

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

C.6

in place for its educational programmes

Makes two types of brochure and/or packaging adaptations to facilitate
appropriate use by patientsJohnson & Johnson performs strongly in conflict of interest (COI) mitigation for the five

Johnson & Johnson adapts brochures and pack-

AMR-related educational programmes foraging to facilitate the appropriate use of bedaq-

HCPs assessed by the Benchmark. To mitigate

uiline (Sirturo®) by patients. Johnson & Johnson

COI for all five programmes, it provides finan-

performs well, taking account of language andcial resources to independent third parties (Theadherence to treatment. It produces a pack-

Union, the Chinese and Indonesian govern-

age insert with information in four languages toments) to carry out the programme.

streamline distribution. Further, it packaged a
6-month treatment regimen in a single bottle to

C.5

Engages in sales practices but does notfacilitate patient adherence to treatment.

engage in marketing practices to addressappropriate use
Johnson & Johnson performs above averagein sales practices. It does not deploy any sales

C.7

Active in one AMR surveillance programme; shares raw data in a restricted
manneragents to promote bedaquiline (Sirturo®) toJohnson & Johnson runs the multinational

healthcare professionals except in one country.

Drug Resistance Emergence Assessment in

However, for the remaining antibacterial and/or

MDR-TB (DREAM) programme, which is focused

antifungal medicines it does not report whether

on resistance against bedaquiline (Sirturo®) init decouples incentives for sales agents from11 countries and has been running since 2015.

sales volumes to help prevent the inappropriate

Johnson & Johnson shares the raw data (fromuse of such medicines.

its clinical trials) through the Yale University

Johnson & Johnson does not engage inOpen Data Access (YODA) platform, which canmarketing practices that aim to address the

only be accessed via approval through an inde-appropriate use of its antibacterial and/or anti-

pendent scientific committee.

fungal medicines as its marketing materials do not reflect emerging resistance trends
or include treatment guidelines for healthcare
professionals.

113

Antimicrobial Resistance Benchmark 2021

MRC

Overall Performance
2020

2021

49% 46%▼

Access to Medicine Foundation

Merck & Co, Inc (MSD)
Large R&D-based pharmaceutical company
Stock exchange: NYSE • Ticker: MRK • HQ: Kenilworth, NJ, US • Employees: 74,000

MRC
PERFORMANCE

Performance in the Benchmark

MSD performs below average overall in its evaluated Research Areas0%

compared to the other large research-based pharmaceutical companies
in scope.
R&D: MSD is a middle-performing company in the R&D Research Area.
Its 13-project pipeline has three vaccines. Three projects target critical
and/or urgent pathogens. MSD has made a general commitment toexpanding access to its products.
Responsible Manufacturing: Performs well. Reports environmental risk-

Appropriate Access: Performs less well. Discloses limited information

product.
Stewardship: Middle-performing. It fully decouples incentives for sales
agents from antibacterial sales volumes in the UK. It publicly shares
aggregated results of its surveillance programmes. It reports broad
conflict of interest mitigation for its educational programmes. It does not

50%

100%

Points47%

R&D

14/ 3073%

Manufacturing

11/ 1529%

Access

10/ 3555%

Stewardship0%

11/ 2050%

100%

How Merck & Co was evaluatedon registration filings for its on- and off-patent products. Discloses somestrategies to expand access and ensure continuous supply of its relevant

/ 100
46/

Performance by Research Area

management strategy for own sites and suppliers; quantifies discharge
levels at own sites.

Points46%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

adapt brochures of packaging for patients.
● ● ● Scored●

Not scored

OPPORTUNITIES FOR MSD

CHANGES SINCE 2020

Develop and disclose project-specific plans to improve access and stewardship for R&D projects• In May 2020, MSD’s technology and services

in late-stage development. MSD reports a commitment to expand access through broad registra-provider ILUM Health Solutions combinedtion, including in LMICs, and supports appropriate and responsible use of their antibacterial medi-with UPMC Infectious Disease Connect Inc.

cines. MSD can develop project-specific access and stewardship plans for all its late-stage R&D pro-to share expertise and resources to enhance

jects. For example, for its S. pneumoniae vaccine V116 it can commit to fast registration in countries

patient care, optimise antimicrobial therapy

with the highest burden of disease, and develop a pricing strategy that considers the ability to payof target populations in those countries.

and reduce potential for drug resistance.
• In 2020, MSD expanded the functionality of

Expand its environmental risk-management strategy to suppliers and ensure compliance at all

the global SMART surveillance website, and itsites with antibacterial discharge limits by tracking and publicly disclosing progress and results.

will put a mechanism in place for researchers

MSD reports to set limits and to quantify the discharge levels at its own sites. It can extend thisto request access to anonymised raw data.

practice to suppliers’ sites and track compliance of both own and suppliers’ sites with discharge
limits and publicly disclose the results. To provide clear evidence of its progress, it can publicly
report compliance at all sites. Disclosure of information, including the results of audits and antibacterial discharge levels of its own sites and suppliers’ sites, is important. It can also publicly disclose
the names and locations of its suppliers and waste-treatment plants for increased transparency.
Expand registration of medicines and vaccines to more access countries. MSD reports thatceftolozane/tazobactam (Zerbaxa®) was filed for registration in 25 access countries. It can file its
antibacterial and antifungal medicines and vaccines (e.g. Zinplava™, Recarbio™ and Pneumovax
23®) in more countries, including low-income countries, with a high burden of disease. It can
improve disclosure on where its medicines are registered and made available.
Fully decouple incentives for sales agents from sales volumes. MSD runs a pilot in the UK, in which
it fully decouples incentives for sales agents from sales volumes of antibacterial medicines sold in
UK hospitals. It can expand this practice to all countries it operates in and to all antibacterial andantifungal medicines.
Publicly share raw data from surveillance programmes. MSD runs multiple AMR surveillance programmes. It can publicly share raw data from these surveillance programmes: SMART, PACTS andSTAR - anonymised and in a freely accessible format. Additionally, either MSD or the managing partners can publicly share raw data from the CANWARD and BSAC surveillance programmes.

* All companies were assessed based ondata submitted to the Benchmark in thecurrent and previous periods of analysis, as well as information the companies have made publicly available, or thatare accessible through other sources.
For the 2021 Benchmark, MSD declined
to submit data to the Antimicrobial
Resistance Benchmark.

114

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONSMRCNet sales by business segment

Therapeutic areas: Cardiovascular, Diabetes, Hospital acute care,2019 4,393

Immunology, Neuroscience, Oncology, Vaccines, Virology.

2020 4,703

Business segments: Animal health, Pharmaceuticals

0

Product categories: Animal health, Innovative medicines, Vaccines
M&A since 2020: None in the antibacterial and/or antifungal sectors

41,751

175

43,021
10,00020,000

Animal Health30,000

Pharmaceuticals

23

40,00050,000
Other segment sales mn USD

MRC
Net sales by region
201920,5192020

21,0270

10,00012,707
13,60020,00030,00040,00050,000Asia Pacific (other than China and Japan) mn USD
Latin America
Other

United States
Europe, Middle East and Africa
China
Japan

PIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 13 projects targeting pathogens in scope** (10 antibacterial

Comparatively small portfolio: At least 19 products: 12 antibacterial medi-

medicines; 3 antibacterial vaccines).

cines; 4 antibacterial vaccines; 3 antifungal medicines

Development stages: 2 clinical projects, including V116, a Phase II pneumo-

On-patent medicines: 6 (bezlotoxumab, ceftolozane/tazobactam, fidax-

coccal vaccine; and 7 discovery/preclinical projects.

omicin, imipenem/cilastatin/relebactam, posaconazole, tedizolid)

Novelty: 0 novel clinical-stage medicine projects.

On-patent vaccines: 3 (Liquid PedvaxHIB®, Pneumovax® 23, Vaxelis®)‘Critical’ and/or ‘urgent’ pathogens: 3 projects, relebactam/imipenem/

Off-patent/generic medicines: 7 of 10 were selected for analysis** (ben-cilastatin (Recarbrio™) targets carbapenem-resistant Enterobacteriaceae.

zathine benzylpenicillin [A], caspofungin [F], clotrimazole/betamethasone

It is active against Klebsiella pneumoniae carbapenemase (KPC), but[F], daptomycin [R], ertapenem [W], gentamicin [A], moxifloxacin [W])not metallo-beta-lactamase (MBL)- producing Enterobacteriaceae.

AWaRe medicines***: 2 Access group; 4 Watch group; 2 Reserve group

Fidaxomicin (Dificid®) targets C. difficile.
Regulatory approvals: 4 approvals. In July 2019, Relebactam/imipenem/

MRC
Pipeline for priority pathogens

cilastatin (Recarbrio™) was approved by the FDA for the treatment ofcomplicated urinary tract infections (cUTI), including pyelonephritis, andcomplicated intra-abdominal infections (cIAI). In June 2020, Recarbrio™
received supplemental approval by the FDA for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP)

30ugate vaccine (15-valent) was approved by the FDA.

1020● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

MRC
Products on the market

in adults. In January 2020, Fidaxomicin (Dificid®) paediatric adaptation wasapproved by the FDA. In July 2021, Vaxneuvance™, pneumococcal coni-

10

4
0

12
10

3
20

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority** bacteria & fungi

Pipeline targeting priority pathogens: 13 As at 24 September 2021
Discovery

Pre-clinicalProtein synthesis inhibitor [M. tuberculosis]♦ Shigella spp. vaccine

Partnership with Orchid
Pharma, India - Bacteria & fungi

Compound screening
ALIS (MOA) [M. tuberculosis]
ATP synthase inhibitor
1 mo GLP safety studies[M. tuberculosis]
In vivo preclinical PK/PD
dose ranging project [M.
tuberculosis]
Diarylquinoline (TBAJ587) [M. tuberculosis]

Phase I

Phase II

Phase III

Approval♦ S. pneumoniae vaccine
adult (V116)

Sivextro® - additional
population: paediatric[Gram positive bacteria](Vaxneuvance™)[FDA/Jul-21]†♦ S. pneumoniae vaccine

Fidaxomicin (Dificid®) [C.
difficile] [FDA: Jan-20]:
additional population:
paediatricRelebactam/imipenem/
cilastatin (Recarbrio™)[Enterobacteriaceae][FDA/Jul-19] cUTI,
including pyelonephritis
and cIAI[FDA/Jun-20] HABP/
VABP** See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
*** Listed on the 2019 WHO EML.

♦ = Vaccine
GLP = Good Laboratory practice
PK/PD = Pharmacokinetic/pharmacodynamiccUTI = Complicated urinary tract infection
cIAI = Complicated intra-abdominal infection
HABP = Hospital-acquired bacterial pneumonia
VABP = Ventilator-associated bacterial pneumonia† Approved after the end of the period of analysis.

115

Antimicrobial Resistance Benchmark 2021

A.1

Investments in R&D

Access to Medicine Foundationfrom the FDA for the treatment of complicatedControl and Prevention (CDC). Relebactam/imi-

MSD does not disclose publicly, or to theurinary tract (cUTI) and intra-abdominal infec-

penem/cilastatin (Recarbrio™) targets carbap-

Benchmark, its R&D investments during 2019

tions (IAI). Recarbrio™ does not meet any ofenem-resistant Enterobacteriaceae, and fidax-

and 2020 in antibacterial and antifungal med-WHO’s innovativeness criteria. MSD has threeomicin (Dificid®) targets C. difficile.

icines and/or vaccines for pathogens in scope.

adaptive projects aiming, respectively, to extend

MSD has pledged USD 100 mn to the AMR

the indications of fidaxomicin (Dificid®), rele-

Action Fund over the next ten years.

bactam/imipenem/cilastatin (Recarbrio™) andtedizolid (Sivextro®).

A.2.1 Medium-sized pipeline

A.3

General commitments towards expanding access and affordability practices

MSD does not report any specific access or
stewardship plans for any of its six late-stage

The company has 13 projects targeting patho-

A.2.3 Three vaccine candidates

medicine and vaccine projects targeting path-gens in scope: 10 medicines and three vaccines,

MSD reports three vaccine projects in its pipe-

ogens in scope. Four out of six projects have

all targeting bacterial pathogens. Out of the 13

line. It includes one innovative candidate in pre-ongoing clinical trials in access countries.‡ The

projects, two are in discovery stage, five are inclinical development targeting Shigella spp. andcompany has made a general commitment about

preclinical development, two are in clinical devel-

two adaptive vaccine candidates targeting S.

registering its products in LMICs, expanding

opment and four received marketing approval.

pneumoniae: V114 and V116.

access through broad registration and improving

A.2.2 MSD extending indications for their

A.2.4 Two candidates targeting critical and/or

affordability. MSD supports the appropriate andurgent priorities

antibacterials
MSD’s clinical-stage medicine pipeline consists

MSD has two medicines in its R&D pipeline tar-of both innovative and adaptive R&D projects.

geting pathogens defined as ‘critical’ by WHO’s

Relebactam/imipenem/cilastatin (Recarbrio™)

list of priority pathogens and/or characterised

received first marketing approval in July 2019as ‘urgent’ threats by the US Centers for Disease

responsible use of its antibacterial and antifungal medicines by supporting hospitals globally tostrengthen their AMS programmes.

B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Environmental risk-management for own

mental standards. It reports auditing externalsites and suppliers; sets limits at own

private and public waste-treatment plants but nosites and suppliers

details on audit parameters are provided. It also

MSD reports a strategy to minimise the envi-

does not report whether conservative measuresronmental impact of wastewaters and solidfor effluents sent to external public wastewater

waste from antibacterial manufacturing at its

plants are employed.

sites, including audits at least every 1-2 years. It

discharge from its own or suppliers’ sites.
B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

MSD reports that its own sites and suppliers
have a system to maintain high-quality antibac-

Publicly discloses some information on

terial production, consistent with international

environment for all antibacterials manufactured

environmental risk management and

GMP standards. This includes risk-based inter-at its sites, based on PNECs to limit AMR, as rec-commitment to setting limits

nal audits and tracking of corrective and preven-ommended the AMR Industry Alliance. It also

MSD publishes some components of its envi-

tive actions. It also requires its suppliers to audit

reports quantifying discharge levels but there isronmental risk-management strategy. It is atheir own suppliers. The Benchmark found nono information on the methods used and compli-

member of the AMR Industry Alliance, which

requests for official corrective action from theance with set limits.

publishes a list of recommended antibacte-

FDA or EMA related to non-conformities with

MSD requires third-party suppliers of anti-

rial discharge targets. MSD publishes its com-cGMP at MSD’s own sites or any subsidiaries thatbacterials to follow similar standards, including

mitment to setting these targets. It does not

manufacture antibacterials.

on-site audits and limits based on PNECs. Therepublish: (1) the results of environmental audits,

is limited information whether it requests andwhether conducted at its own sites, the sites

reviews the discharge levels of its suppliers.

of suppliers or external private and public

reports setting discharge limits in the receiving

MSD expects external private waste-treatment plants to comply with its general environ-C

B.2

waste-treatment plants; (2) a list of these suppliers and plants; or (3) the levels of antibacterial

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries‡
C.1.1

Limited information on registration fil-of filing its seven relevant off-patent/generic

patents in low-income countries. MSD does notings for on-patent medicines

medicines for registration in access countries.

provide evidence of patient reach and geographic

MSD performs below average as it does not disclose where it has filed five of its six relevant
on-patent medicines for registration. However,reach in low- and middle-income countries.
C.1.3 No information on registration filings foron-patent vaccines

it publicly reports that its on-patent medicine,

MSD reports no evidence of filing its three rel-ceftolozane/tazobactam (Zerbaxa®), a reserve

evant on-patent vaccines for registration in

antibiotic used to treat intra-abdominal infec-

access countries.

tions, acute pyelonephritis, cUTIs and hospital-acquired pneumonia, was filed for registration in 25 LMICs.

C.2.2 Limited information on strategies toexpand access to off-patent/generic
medicines
MSD’s performance is low as it discloses limited information on how it expands access to its

C.2.1 Limited information on strategies toexpand access to on-patent medicinesseven relevant off-patent/generic medicines. It
publicly reports to expand access through differ-

MSD performs below average. It expands accessential pricing and public or private partnerships

to its on-patent medicines in access countries

with governments, NGOs and distribution chan-ings for off-patent/generic medicines

through differential pricing and public or private

nels. MSD does not provide evidence of patient

MSD’s performance is low. It reports no evidence

partnerships and publicly commits not to enforce

reach and geographic reach.

C.1.2 Limited information on registration fil-‡ 102 low- and middle-income countries
where better access to medicine is mostneeded.

116

Antimicrobial Resistance Benchmark 2021

C.2.3 Limited information on strategies toAccess to Medicine Foundation

intra-country pricing strategies to allow for pricemedicines and vaccines. MSD has supply agree-

flexibility. MSD publicly commits not to enforce

ments with local manufacturing partners to

MSD performs below average as it discloses lim-

patents in low-income countries. MSD does

allow for local production of its vaccine. To miti-

ited information on how its expands access to its

not provide evidence of patient reach and geo-

gate against substandard and falsified products,

on-patent vaccines in access countries. It pub-graphic reach for its strategies.

MSD uses security features, has a dedicatedexpand access to on-patent vaccines

licly discloses having differential pricing andintellectual property policies, and participating in

anti-counterfeiting team in place, and raises
C.3

Limited information on strategies to

its vaccines, MSD takes into account the level of

MSD has an average performance. It publicly

economic development, the channel of distribu-

reports to ensure accurate demand planning andtion and the public health needs. It has inter- andcommits to maintaining a reliable supply of itsCpublic awareness.

ensure continuous supply

public or private partnerships. To set the price of

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Broad COI mitigation strategies in placedecouples incentives for sales agents from sales

been running since 2002. MSD only sharesfor its educational programmes

volumes to help prevent the inappropriate use of

the aggregated results through peer-reviewed

its antibacterial and/or antifungal medicines.

open-access journal articles as well as on the

MSD performs well in the analysis of its top
five AMR-related educational programmes for

MSD engages in marketing practices thatonline SMART database, a restricted data

healthcare professionals in conflict of inter-

aim to address the appropriate use of its anti-

platform. Additionally, it is planning to makeest (COI) mitigation. To mitigate COI for threebacterial and/or antifungal medicines. Its mar-anonymised source data available for research-

programmes, it provides financial resources toketing materials reflect emerging resistanceers upon request through the SMART database.

independent third parties (CIDEIM, BSAC andtrends and/or include treatment guidelines for

For the remaining programmes, only the aggre-

the University of Dundee) to develop the pro-healthcare professionals: it has developed its

gated results are shared through peer-reviewed

gramme. One programme (developed by theStar of Stewardship principles in which all mar-open-access journal articles, as well as on ancompany) has all three COI mitigation strate-keting materials must include, e.g. specific indi-

open-access data platform for the CANWARD

gies looked for by the Benchmark: (1) content

cations, treatment duration and dose.

programme (a national programme managed byis developed by a third party independent fromthe company’s own marketing department; (2)the Canadian Antimicrobial Resistance Alliance).
C.6

Does not report adapting brochures and/or packaging to facilitate appropriate

participants are not provided financial or mate-use by patients

rial incentives (as it is a website); and (3) it does
not use branded materials. The remaining pro-

MSD does not report adapting brochures and/gramme has one COI mitigation strategy: it isor packaging to facilitate the appropriate use of

unclear whether content is developed inde-

its antibacterial and/or antifungal medicines bypendently from its marketing department or

patients.

whether it uses branded materials.
C.7
C.5

Engages in sales and marketing practices
to address appropriate use

Active in multiple AMR surveillance programmes; openly publishes aggregatedresults

MSD performs above average in sales prac-

MSD is active in multiple AMR surveillance pro-tices. It started a pilot in 2019 where it does

grammes. It runs the multinational SMART pro-not reward its sales agents based on antibacte-gramme, which is focused on respiratory infec-

rial volumes sold in UK hospitals. However, out-tions and complicated intra-abdominal and uri-side of this pilot MSD does not report whether itnary tract infections in 63 countries and has

117

Antimicrobial Resistance Benchmark 2021

NVR

Overall Performance
2020

2021

54 % 63%▲

Access to Medicine Foundation

Novartis AG
Large R&D-based pharmaceutical company
Stock exchange: SWX • Ticker: NOVN • HQ: Basel, Switzerland • Employees: 105,794

NVR
PERFORMANCE
Novartis performs above average overall in its evaluated Research Areas
compared to the other large research-based pharmaceutical companies

Performance in the Benchmark

0%

in scope.
R&D: Novartis no longer carries out R&D projects that target pathogens
in scope of the AMR Benchmark.
Responsible Manufacturing: Performs strongly. Reports comprehensive
environmental risk-management strategy for own sites and suppliers;
co-leads in reporting compliance with limits at own sites, audits external
private and public waste-treatment plants.

countries. Reports several strategies to expand access and ensuresignificant portion of its sales by using tenders. It supports a surveillance
programme in Poland of which aggregated results are publicly shared. It
reports comprehensive conflict of interest mitigation for its educational
programmes. It adapts brochures for patients.

50%

100%

Points

7%

R&D

1/ 15

87%

Manufacturing

13/ 1580%

Access12/ 1575%

Stewardship0%

15/ 2050%

100%

How Novartis was evaluatedcontinuous supply of its relevant products.
Stewardship: Performs well. It decouples sales incentives for a

/ 65
41/

Performance by Research Area

Appropriate Access: Performs strongly. Files some of its relevant
products (on- and off-patent products) for registration in access

Points63%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR NOVARTISCHANGES SINCE 2020Engage in antibacterial and antifungal R&D including medicines and vaccines against priority• Approval secured of a OneNovartis AMR pro-pathogens. Novartis contributes to the AMR Action Fund, a joint venture that aims to bring 2-4 newgram to minimise spread of AMR by focus-

antibiotics to the market by 2030 and has a partnership with GARDP to provide antibiotic formu-

ing efforts where the company can make a dif-lations accessible for children with drug-resistant infections. Novartis can engage in in-house R&D,

ference. The programme prioritises appro-through acquisition or collaboration with other companies, or by joining existing public private part-

priate access, responsible manufacturing andnerships, to target resistant pathogens for which R&D is limited, such as Campylobacter spp. and H.

responsible use. The initiative was launched inpylori.

May 2021.

Ensure compliance to antibacterial discharge limits at suppliers sites by tracking and publicly dis-

• In July 2020, Sandoz and the Austrian govern-

closing progress and results specific to antibacterials for all sites. Novartis can expand its require-ment formed a public-private partnership toments to quantify discharge levels as it does for its own sites to all its suppliers’ sites and track

increase production capacity at Sandoz’s anti-

compliance with set limits. It can publicly disclose the results including the discharge levels. The

biotics manufacturing site in Kundl, Austria.

company currently publishes information on compliance at own sites with pharmaceutical limits

Sandoz commits to investing more than USD

that include, but is not specific to, antibacterials. Novartis can also apply limits directly in effluent to

175 mn over the next five years to new antibi-

fully mitigate AMR risk.
Expand registration and ensure availability of antibacterial and antifungal medicines. Novartis

otics manufacturing technology.
• Novartis has expanded registration of its

can expand registration of its antibiotics and antifungals listed on the 2021 WHO EML, such as dap-

sample off patent/generic medicines to more

tomycin and tigecycline, to more countries, including low-income countries, with a high burden ofaccess countries, meeting the opportunity

disease.

provided in the 2020 Benchmark.

Fully decouple incentives for sales agents from sales volumes. In Novartis’ limited promotional• Since 2019, Novartis supports the Diagnostics

activities directed at healthcare professionals, it links part of its sales agents’ incentives to salesof Central Nervous System Bacterial Infections

volumes of antibacterial and antifungal medicines. It can fully decouple such incentives for sales(KOROUN) study, a national AMR surveillance

agents.

programme focused on community-acquired

Publicly share raw data from surveillance programme. Novartis supports the national Diagnostics

respiratory tract infections in Poland. Before

of Central Nervous System Bacterial Infections (KOROUN) programme, which is managed by thethis programme Novartis was not involved in

Polish National Medicines Institute. Either Novartis or the managing partner can publicly share raw

AMR surveillance.

data from this surveillance programme.

118

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

NVR
Net sales by business segment

Therapeutic areas: Cardiovascular, renal and metabolism; Immunology,

2019

hepatology and dermatology; Neuroscience; Oncology; Ophthalmology;

2020

Respiratory.

37,71439,0130

Business segments: Innovative Medicines, Sandoz

10,00020,000Innovative Medicines

Product categories: Biosimilars, Generic medicines, Innovative medicines

9,731

30,0009,646

40,00050,000mn USD

SandozNVR
Net sales by region

M&A since 2020: In February 2021, Novartis division Sandoz signed anagreement to acquire GSK’s cephalosporin antibiotic business for USD 350
mn in addition to milestone payments up to USD 150 mn.

2019

17,933

19,7132020

18,715

19,7250

10,000EuropeAmericas20,00030,0009,799
10,21940,000Asia/Africa/Australasia

50,000mn USDPIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Novartis is currently not developing any projects targeting the pathogens

Comparatively large portfolio: At least 109 products: 96 antibacterial med-in scope*.

icines; 13 antifungal medicines
Off-patent/generic medicines: 10 of 109 were selected for analysis*(amoxicillin [A], amoxicillin/clavulanic acid [A], clarithromycin [W], daptomycin [R], itraconazole [F], levofloxacin [W], linezolid [T], rifampicin [T],tigecycline [R], voriconazole [F])AWaRe medicines**: 21 Access group; 35 Watch group; 2 Reserve groupAnti-TB medicines**: 9NVR
Pipeline for priority pathogens
0
0

10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

NVR
Products on the market
96 13
0

20

40

60

80

100

120

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Investments in R&D

A.2.2 Novelty of pipeline

A.3

Novartis did not report investments during 2019

Novartis is not eligible for this indicator as it

Novartis is not eligible for this indicator as it has

and 2020 in R&D for antibacterial and antifun-

does not have any R&D candidates in clinicalno projects targeting pathogens in scope in late-

gal medicines and/or vaccines for pathogens indevelopment.

stage clinical development.

scope. Novartis has pledged an unknown

Access and stewardship planning

Companies are expected to have plans in placeamount to the AMR Action Fund over the next

A.2.3 Not active in vaccine development

10 years.

Novartis is not active in vaccine development

for pipeline projects in Phase II and beyond.

targeting pathogens in scope.
A.2.1 Novartis does not engage in R&D for
products in scope

A.2.4 Critical and/or urgent priorities

The company does not report any project in its

Novartis is not eligible for this indicatorpipeline targeting pathogens in scope.

as it does not have any R&D candidates indevelopment.

Pipeline targeting priority pathogens: 0 As at 24 September 2021
Discovery

Pre-clinical

Phase I

Phase II

Phase III

Approval

Novartis is currently not developing any projects targeting the pathogens in scope*.

* See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
** Listed on the 2019 WHO EML.

119

Antimicrobial Resistance Benchmark 2021

Access to Medicine FoundationB

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Comprehensive environmental risk-man-

suppliers. It is undisclosed how many of the 160

terials. It publicly discloses that 80% of its own

agement for own sites and suppli-

supplier sites report to have quantified discharge

sites are compliant to these general limits. The

ers; audits external private and public

levels.

discharge levels themselves are not published.

waste-treatment plants

Novartis expects external private

Novartis also does not publish: (1) the results ofNovartis reports a comprehensive strategy towaste-treatment plants to comply with its gen-environmental audits, conducted at its own sites,

minimise the environmental impact of waste-eral environmental standards. It audits exter-

the sites of suppliers and/or external private andwaters and solid waste from antibacterial man-nal private and public waste-treatment plants at

public waste-treatment plants; or (2) a list ofufacturing at its sites, including audits every 2-4

least every three years, based on risk. It requests

these suppliers and plants.

years. It reports setting discharge limits in theexternal private and public wastewater treat-

receiving environment for all antibacterials man-ment plants to provide dilution and flow rate

ufactured at its sites, based on PNECs to limit

data to inform the mass balance approach and

AMR, as recommended by the AMR Industry

employs conservative measures when needed.

Alliance. Discharge levels are quantified at all

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

Novartis reports that its own sites and suppliers
Publicly discloses some information on

have a system to maintain high-quality antibac-

analysis, as applicable. It reports that complianceenvironmental risk management andterial production consistent with internationalof own sites with discharge limits is tracked. Itcompliance with limits for pharmaceuti-

GMP standards. This includes periodic risk-

also publicly reports that 80% of its own sites

cals including antibacterials

based audits and tracking of corrective and pre-sites using a mass balance approach or chemical

B.2

are compliant with discharge limits for pharma-

Novartis publishes some components of its envi-

ventive actions. Novartis also requires its suppli-

ceuticals which include, but are not specific to,ronmental risk-management strategy. It is a

ers to audit their own suppliers. The Benchmark

antibacterials.

member of the AMR Industry Alliance, whichfound no requests for official corrective action

Novartis requires third-party suppliers of

publishes a list of recommended antibacterial

from the FDA or EMA related to non-conformi-

antibacterials to follow the same standards,

discharge targets. Novartis publishes its com-ties with cGMP at Novartis’ own sites or any sub-including limits based on PNECs. It reports con-mitment to setting discharge limits, at own andsidiaries that manufacture antibacterials.

ducting on-site audits every three years. It

suppliers’ sites, for pharmaceuticals in the envi-

requests and reviews the discharge levels of its

ronment which include but go beyond antibac-

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Novartis is not eligible for indicators: C.1.1, C.1.3,

to sell some of its medicines, of which antibiot-

C.2.1 and C.2.3. For more information, see

ics used to treat patients with COVID-19-related

Appendix VII.

symptoms, at zero-profit to governments in up
to 79 eligible low-income and lower-middle-in-

C.1.2 Filed to register off-patent/generic med-come countries.

icines in 30 access countries on average
Novartis performs above average, filing nine ofits 10 relevant off-patent/generic medicines for

C.3

Several strategies to ensure continuous
supplyregistration in 30 access countries on average.

Novartis performs above average, with strate-

Its most widely filed relevant product is amox-

gies reported in all four areas assessed. Novartis

icillin/clavulanic acid, filed in 70 access coun-ensures accurate demand planning and data

tries. Three of its relevant products are filed insharing by following a monthly rolling processless than ten access countries. Six of its rele-

from one to 36 months in advance and ensuresvant products are filed for registration in at least

weekly data sharing for anti-infectives. Novartis

one LIC.

mitigates against shortage risks by keeping
buffer stocks for key starting materials, drug

C.2.2 Several strategies to expand access tosubstance and drug products. It ensures dual

off-patent/generic medicines

sourcing when possible. It has set daily, weekly,

Novartis performs above average, with accessand monthly KPIs to monitor its supply chain

strategies reported for four of its ten relevant

performance. Novartis reports one technology

off-patent/generic medicines. It aims to expand

transfer initiative in Pakistan, to locally produce

access to its off-patent/generic medicines in

its penicillin portfolio. To mitigate against sub-access countries through equitable pricing, ten-standard and falsified products, Novartis moni-ders and competitive prices. It provides evidence

tors online platforms, uses data analytics, spec-of patient reach and geographic reach for all its

trometry technologies, anticounterfeiting pack-reported approaches. Novartis Access pricing

aging features and mobile applications.

policy ranges the prices from USD 1 per treatment per month or at tailored prices. Novartis
Sub-Saharan African (SSA) Unit takes a high-volume, lower-price approach to increase thepatient reach. Novartis has set public goals toincrease the patient reach twofold by 2022 andfivefold by 2025 through its SSA unit. In 2020,
Novartis, through its Sandoz division, committed*** 102 low- and middle-income countries where better access to medicine ismost needed.

120

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

antibacterial and/or antifungal medicines. Its(KOROUN) programme, which is managed by thein place for its educational programmesmarketing materials include emerging resist-

Polish National Medicines Institute with support

Novartis performs strongly in conflict of interest

ance trends and/or include treatment guide-from Novartis and has been running since 2019.

(COI) mitigation for the five AMR-related edu-

lines for healthcare professionals: for azithromy-

It is focused on community-acquired respiratory

cational programmes for HCPs assessed by thecin, cefixime, amoxicillin/clavulanic acid and cef-

tract infections in Poland. Only the aggregatedBenchmark. To mitigate COI for one programme,

podoxime by including antimicrobial steward-

results are shared through open-access journal

it provides financial resources to an independ-

ship guidelines for healthcare professionals andarticles and the KOROUN website.

ent third party (MedShr) to develop the pro-by combining the most recent information fromgramme. The remaining four programmes haveWHO’s AWaRe categorisation with informa-

all three COI mitigation strategies looked for bytion on resistance closely aligned with national

the Benchmark: (1) content is developed inde-

guidelines for its top ten global antibacterial

pendently from its marketing department; (2) amedicines.

pledge not to provide financial or material incentives to participants; and (3) it does not use

C.6

Makes one type of brochure and/or
packaging adaptation to facilitate appro-branded materials.

priate use by patients
C.5

Engages in sales and marketing practices

Novartis adapts brochures to facilitate theto address appropriate use

appropriate use of amoxicillin/clavulanic acid

Novartis performs above average in sales prac-by patients. Novartis is middle-performing intices. It reports that it sells a significant portion

this measure, taking account of paediatric use.

of its antibacterial and/or antifungal medicines

It has created paediatric guidance for amoxicil-

through tenders and does not have sales incen-

lin/clavulanic acid that focuses on correct dosing

tives linked to the sales volume of these tenders.

for children.

Outside of these tenders, promotion of antibacterial and/or antifungal medicines is limited andthe focus of such promotional activities is not onthese medicines.

C.7

Active in one AMR surveillance programme; openly publishes aggregatedresults

Novartis engages in marketing practices

Novartis is active in the national Diagnostics ofthat aim to address the appropriate use of its

Central Nervous System Bacterial Infections

121

Antimicrobial Resistance Benchmark 2021

OPC

Overall Performance
2020

2021

52 % 57% ▲Access to Medicine Foundation

Otsuka Pharmaceutical Co, Ltd
Large R&D-based pharmaceutical company
Stock exchange: TSE • Ticker: 4578 • HQ: Tokyo, Japan • Employees: 5,657

OPC
PERFORMANCE
Otsuka performs average overall in its evaluated Research Areas

Performance in the Benchmark

0%compared to the other large research-based pharmaceutical companies
in scope.
R&D: Otsuka performs well in R&D. All four projects in its pipeline
are antibacterial medicines: three targeting M. tuberculosis and one
targeting a critical and/or urgent pathogen (P. aeruginosa). It has one
novel antituberculosis candidate in clinical development. Otsuka has two
projects in late-stage development with comprehensive plans for accessenvironmental risk-management strategy but without a specific aim to(on-patent medicine) for registration in access countries. Reports somestrategies to expand access and ensure continuous supply of its relevant
product.
Stewardship: Middle-performing. It does not promote delamanid(Deltyba®) to healthcare professionals which is its only product in

50%

100%

Points56%

R&D

14/ 25

43%

Manufacturing

6/ 14

60%

Access

9/ 15

65%

Stewardship0%

13/ 2050%

100%

How Otsuka was evaluatedlimit AMR.
Appropriate Access: Middle-performing. Files its relevant products

/ 74
42/

Performance by Research Areaand stewardship.
Responsible Manufacturing: Performs low. Reports a general

Points57%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

scope. It is not involved in AMR surveillance programmes. It reports
comprehensive conflict of interest mitigation for its educational
programme. It adapts brochures for patients.

● ● ● Scored●

Not scored

OPPORTUNITIES FOR OTSUKA

CHANGES SINCE 2020

Expand breadth of R&D pipeline into more pathogens. Despite being the smallest of the large• In February 2020, Otsuka joined the Project to

R&D-based companies assessed in the AMR Benchmark, Otsuka optimises its resources and has

Accelerate New Treatments for Tuberculosis

achieved remarkable expertise in tuberculosis R&D, being one of the main investors in TB R&D(PAN-TB), a collaboration among philan-

worldwide. Otsuka can now redirect this expertise and invest in innovative in-house R&D to target

thropic, non-profit and private sectors part-

resistant pathogens for which R&D is limited, such as Campylobacter spp. and H. pylori, throughners that aims to develop an investigational

acquisition or collaboration with other companies, or by joining existing public private partnerships.

drug regimen capable of treating all forms ofDevelop an AMR-specific environmental risk-management strategy and increase public disclo-

TB.

sure. Otsuka reports a commitment to manufacture its products in an environmentally responsible• In September 2020, the European Medicinesmanner without specifying whether AMR is taken into account. The company can develop an AMR

Agency (EMA) approved the extension ofstrategy for its own manufacturing sites, the sites of suppliers and external private waste-treat-

Otsuka’s MDR-TB treatment delamanid

ment plants, based on the guidelines of the AMR Industry Alliance, of which Otsuka is a member.

(Deltyba®) to include children with a bodyThis includes setting limits and quantifying discharge levels to track compliance. Moreover, Otsuka

weight of at least 30 kg. In July 2021, the EMA

can publish information on how it manages environmental risk related to antibacterial manufactur-

approved the use of the 25 mg dispersible

ing to curb AMR.

tablet formulation of delamanid (Deltyba®) for

Ensure availability and affordability of delamanid (Deltyba®). Otsuka can expand the availability ofthe treatment of pulmonary MDR-TB in adults,

delamanid (Deltyba®) by filing for registration in more access countries, including through its vol-adolescents, children and infants with a bodyuntary licensing agreement with Viatris, in particular in the 30 countries with the highest MDR-TB

weight of at least 10 kg.

burden identified by the WHO.
Engage in AMR surveillance activities. Otsuka is not active in AMR surveillance activities. It canengage in AMR surveillance programmes through setting up (in-house) programmes or by funding
established programmes run by research organisations. Additionally, Otsuka should publicly shareraw data collected from the programme.

122Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

OPC
Revenue by business segment

Therapeutic areas: Cardiovascular and renal diseases, Central nervous

2019

system, Oncology, Ophthalmology, Tuberculosis

2020

Business segments: Pharmaceuticals

924,250
955,1590

Product categories: Innovative medicines

200,000

400,000

600,000

800,000

Pharmaceuticals

M&A since 2020: None in the antibacterial and/or antifungal sectors

1,000,000
mn JPY

OPC
Revenue by region
2019

450,2132020

436,8120

200,000

400,000

Japan

North America

Others289,335

184,701

335,396
600,000

182,949

800,000

1,000,000
mn JPYPIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 4 projects targeting pathogens in scope* (4 antibacterial

Comparatively small portfolio: At least 1 product: 1 antibacterial medicine

medicines).

On-patent medicine: 1 (delamanid)

Development stages: 1 clinical project, OPC-167832, a Phase II candidate

AWaRe medicines: 0

for the treatment of M. tuberculosis; and 1 preclinical project targeting P.

Anti-TB medicine**: 1

aeruginosa.
Novelty: 1 novel project, OPC-167832, an antituberculosis candidate that

OPC
Pipeline for priority pathogens

meets all four criteria set by WHO for innovativeness.
‘Critical’ and/or ‘urgent’ pathogens: 1 project, VIS705, a preclinical therapeutic candidate, targeting P. aeruginosa, including MDR strains.

4
0

10

20

Regulatory approvals: 2 approvals. Marketing authorisation by the EMA
was granted to the antituberculosis drug delamanid (Deltyba®) for thetreatment of children with a body weight of at least 30 kg. In July 2021 the
EMA approved the use of the 25 mg dispersible tablet formulation of delamanid (Deltyba®) for the treatment of pulmonary MDR-TB in adults, adolescents, children and infants with a body weight of at least 10 kg.

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

OPC
Products on the market
01
0

10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Investments in R&D

pathogens in scope. All of them are medicines

cine candidate which meets all four WHO’s inno-

Otsuka discloses to the Benchmark its R&D

targeting bacterial pathogens: three are antitu-

vativeness criteria: OPC-167832. In September

investments during 2019 and 2020 in antibac-

berculosis agents and the remaining one tar-

2020, EMA approved the extension of Otsuka’s

terial and antifungal medicines and/or vaccines

gets P. aeruginosa. Out of the four projects, one

MDR-TB treatment delamanid (Deltyba®) tofor pathogens in scope. Otsuka reports that it

is in preclinical stage, one in Phase II, delamanid

include children with a body weight of at least

invested USD 34.61 mn in R&D for antibacte-(Deltyba®) for paediatric patients received mar-

30 kg. In July 2021, the EMA approved the use of

rial medicines in 2019 and 2020. This constitutes

keting approval during the period of analysis andthe 25 mg dispersible tablet formulation of dela-a small proportion of its revenues compared tothe adult indication remains in Phase IV.

manid (Deltyba®) for the treatment of pulmonary MDR-TB in adults, adolescents, children andthe other companies who reported investments
A.2.2 Small innovative pipelineto the Benchmark.

infants with a body weight of at least 10 kg.

Otsuka’s clinical-stage medicine pipeline conA.2.1 Pipeline targets mainly M. tuberculosis

sists of both innovative and adaptive R&D pro-

A.2.3 Not active in vaccine development

The company reports four projects targeting

jects. Otsuka has one antituberculosis medi-

Otsuka is not active in vaccine development tar-

Pipeline targeting priority pathogens: 4*** As at 24 September 2021
Discovery

Pre-clinical
VIS705 [P. aeruginosa]

Phase I

Phase II
OPC-167832 [M. tuberculosis]

Phase III

Approval
Delamanid (Deltyba®)[M. tuberculosis][EMA/Sep-20] additional population: paediatric (>30 kg)[EMA/Jul-21] additional
formulation (25mg)(>10 kg)†*** Includes 1 Phase IV project not shown in the ﬁgure.
† Approved after the end of the period of analysis.
* See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
** Listed on the 2019 WHO EML.

123

Antimicrobial Resistance Benchmark 2021

geting pathogens in scope.

Access to Medicine Foundation

Otsuka has two medicine projects in late-stageensure its appropriate use, as well as availability

development. For its project OPC-167832, inand affordability in access countries†.

Phase II, Otsuka has committed itself conA.2.4

One candidate targeting criticaltractually to a comprehensive access strat-

and/or urgent priorities

egy as stipulated by the Bill & Melinda Gates

Otsuka has one medicine candidate in its R&D

Foundation. Otsuka also reports plans to engage

pipeline targeting pathogens defined as ‘critical’in surveillance and monitoring of the emer-

by WHO’s list of priority pathogens and/or char-gence of resistance to this new antituberculo-

acterised as ‘urgent’ threats by the US Centers

sis candidate.

for Disease Control and Prevention (CDC).
VIS705 is in preclinical development and targets
P. aeruginosa, including MDR strains.

For the paediatric indication of the antituberculosis drug delamanid (Deltyba®) for
which marketing authorisation by the EMA was
granted in September 2020 for children above

A.3

Comprehensive planning for access and

30 kg and on July 2021 for children above 10 kg,

stewardship

Otsuka also has comprehensive strategies to

B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

No AMR-specific environmental risk

B.2

Publicly discloses some information on

subsuppliers of antibacterials. The Benchmark

environmental risk managementfound no requests for official corrective action

Otsuka’s general environmental strategy

Otsuka publishes some components of its envi-

from the FDA or EMA related to non-conform-

includes a commitment to manufacture its prod-ronmental risk-management strategy, with-ities with cGMP at Otsuka’s own sites or any

ucts in an environmentally responsible mannerout specific references to AMR. It is a member

subsidiaries.

but without a specific aim to limit AMR. Its strat-of the AMR Industry Alliance, which publishes amanagement strategy

egy also does not include any actions specific tolist of recommended antibacterial discharge tar-delamanid (Deltyba®), the only antibacterial pro-

gets. Otsuka does not publish: (1) the results of

duced at its manufacturing sites, in both its API

environmental audits, whether conducted at its

and drug product forms.

own sites, the sites of suppliers or external pri-

Otsuka does not report making any require-vate and public waste-treatment plants; (2) a list

ments in this regard to the third-party drugof these suppliers and plants; or (3) the levels of

product manufacturer contracted for an inter-

antibacterial discharge from its own or suppli-

mediate step in delamanid production.

ers’ sites.

There is also limited information on therequirements Otsuka makes of external private

B.3

System in place to maintain production
quality for own and suppliers’ sites; nowaste-treatment plants, in terms of strategy,

requests for official corrective action

audits and discharge limits and levels. It reports
these plants are audited every three years but

Otsuka reports that its own sites and suppliers

audit parameters are not related to AMR. It also

have a system to maintain high-quality antibac-

reports wastewater is treated on-site and exter-

terial production consistent with international

nal private and public wastewater treatment

GMP standards. This includes periodic risk-based

plants are not used.

audits and tracking of corrective and preventive actions. Otsuka reports it does not have any

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries†
Otsuka is not eligible for indicators: C.1.2, C.1.3,

of USD 1,700 for a 6-month treatment course.

data sharing by conducting long-term plan-

C.2.2 and C.2.3. For more information, see

Otsuka has a voluntary licensing agreement withning and S&OP planning. Otsuka mitigates

Appendix VII.

Viatris and R-Pharm to accelerate access toagainst shortage risks by keeping a 1,5-year aver-delamanid (Deltyba®) in high TB burden coun-age buffer stock in the countries where dela-

Filed to register its on-patent medicine

tries. Otsuka and Viatris have entered into amanid (Deltyba®) has a marketing authorisa-

in 9 access countries

technology transfer agreement, to produce andtion. It conducts annual inventory checks andOtsuka has an average performance, filing its

distribute a lower-cost generic version of dela-

external audits of its stocks. Otsuka conducts

one on-patent medicine for registration in nine

manid (Deltyba®). Otsuka provides evidence

a technology transfer to allow Viatris to man-access countries. The medicine is the anti-tuber-of patient reach and geographic reach for its

ufacture, package, and distribute delamanid

culosis medicine, delamanid (Deltyba®).

reported approaches. It estimates that at least(Deltyba®) in a set of access countries. To mit-

24,700 treatment courses were distributed inigate against substandard and falsified prod-

2020. Delamanid (Deltyba®) is available in all 30

ucts, Otsuka uses security features such as seri-

WHO high-burden countries for MDR-TB.

alisation, GS1 barcodes and GDSN traceability.

C.1.1

C.2.1 Some strategies to expand access to its
on-patent medicine

Delamanid (Deltyba®) has a unique packaging

Otsuka has an average performance. It aims to
expands access to its one on-patent medicine inaccess countries through a voluntary licensing

C.3

Some strategies to ensure continuous

process including alu-alu blisters, tamper-proof

supplyseals, and unique identifier codes.

agreement and a partnership. It partners with

Otsuka has an average performance, with

the Global Drug Facility - Stop TB Partnershipstrategies reported in all four areas assessed.

to provide delamanid at a global access price

Otsuka ensures accurate demand planning and† 102 low- and middle-income countries
where better access to medicine is mostneeded.

124

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

healthcare professionals, the company is not eli-in place for its educational programme

gible to be assessed on marketing materials.

Otsuka performs strongly in conflict of interest (COI) mitigation for the one AMR-related

C.6

priate use by patientsby the Benchmark. The programme has all
three COI mitigation strategies looked for by

Makes one type of brochure and/or
packaging adaptation to facilitate appro-

educational programme for HCPs assessed

Otsuka adapts brochures to facilitate the appro-

the Benchmark: (1) content is developed inde-

priate use of delamanid (Deltyba®) by patients.

pendently from its marketing department; (2) a

Otsuka is middle-performing in this measure,pledge not to provide financial or material incen-

taking account of language. It has translated

tives to participants; and (3) it does not use

its Educational Risk Minimisation Materials into

branded materials.

English, French, Spanish and Russian, which are
distributed through the Global Drug Facility.

C.5

Does not promote its antibacterial
medicine

Otsuka performs strongly in sales practices as it

C.7

No involvement in AMR surveillance
programmes

does not promote its product in scope. It does

Otsuka is the only large R&D-based company

not deploy any sales agents to promote dela-that does not report any involvement in AMR

manid (Deltyba®) to healthcare professionals,

surveillance programmes.

because treatment is only available in specialised
centres under tightly controlled conditions. Since
Otsuka does not develop or use marketing materials for delamanid (Deltyba®) to promote it to125Antimicrobial Resistance Benchmark 2021

PFZ

Overall Performance
2020

2021

69 % 81% ▲Access to Medicine Foundation

Pfizer Inc
Large R&D-based pharmaceutical company
Stock exchange: NYSE • Ticker: PFE • HQ: New York, NY, United States • Employees:
78,500PERFORMANCE
Pfizer performs well overall in its evaluated Research Areas compared to

PFZ
Performance in the Benchmark0%

the other large research-based pharmaceutical companies in scope.
R&D: Pfizer performs strongly in R&D. Its 13-project pipeline includes
five vaccines. Seven of its projects target critical and/or urgent
pathogens. It has a novel antifungal in clinical development. Pfizer
reports access and stewardship plans for all eight of its late-stage
projects.
Responsible Manufacturing: Performs strongly. Reports comprehensive

Appropriate Access: Performs strongly. Files some of its on-off-patent

Stewardship: Is the leader. It publicly shares raw data of its ATLAS
surveillance programme. It fully decouples incentives for sales agentsfrom antibacterial sales volumes in the UK. It reports comprehensive
conflict of interest mitigation for its educational programmes. It adapts
packaging for patients.

100%

PointsR&D

77%

23/ 30

Manufacturing

80%

12/ 15

Access80%

28/ 3590%

Stewardship
0%50%

18/ 20100%

How Pfizer was evaluatedproducts for registration in access countries. Reports several strategies
to expand access and ensure continuous supply of its relevant products.

50%

/ 100
81/

Performance by Research Area

environmental risk-management strategy for own sites and suppliers;
quantifies discharge levels at all its own and supplier sites.

Points81%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR PFIZERCHANGES SINCE 2020

Fully decouple incentives for sales agents from sales volumes. Pfizer fully decouples incentives for• In February 2021, BSAC, the European Bank

sales agents from sales volumes of antibacterial medicines in the UK. It can expand this practice tofor Reconstruction and Development, EBRD,

all countries it operates in and to all antibacterial and antifungal medicines.

and Pfizer co-created a global digital learning

Expand breadth of R&D pipeline into more pathogens. Pfizer has the largest late-stage clinicalnetwork for HCPs addressing AMR, antimicro-

pipeline compared to peers in the AMR Benchmark. It has made a series of acquisitions of small bio-

bial stewardship (AMS), and COVID’s impact

tech companies to increase the size of its pipeline. Pfizer can expand the focus of its pipeline totarget resistant pathogens for which R&D is limited, such as Campylobacter spp. and H. pylori.

on AMR and pandemic planning.
• Pfizer is addressing antimicrobial steward-

Ensure compliance with antibacterial discharge limits at suppliers’ sites by tracking and pub-ship health disparities through multiple efforts.

licly disclosing progress and results specific to antibacterials for all sites. Pfizer tracks the com-

As part of its efforts, Pfizer and the Wellcome

pliance of all own sites with set discharge limits. It can also track such compliance of all its suppli-

Trust launched the Surveillance Partnershipers’ sites since Pfizer reports all suppliers have quantified discharge levels and it can publicly dis-to Improve Data for Action on Antimicrobial

close the results. The company currently publishes information on compliance of own and suppliers’

Resistance (SPIDAAR) in July 2020, whichsites with the guidelines of the AMR Industry Alliance but it is unclear whether this includes compli-

is a new collaboration with the governments

ance to discharge limits.

of Ghana, Kenya, Malawi and Uganda to track

Expand registration of Trumenba® and NeisVac-C®. Pfizer can file its vaccines Trumenba® andresistance patterns and better understand the

NeisVac-C® for registration in more countries, including low-income countries with a high burden of
disease.

burden of AMR in LMICs.
• Pfizer purchased shares of ContraFect’s

Expand accessibility of its antibacterial and antifungal medicines in access countries. Pfizer cancommon stock for approximately USD 3 mn.

implement new programmes and partnerships to expand access to its antibacterial and antifungal

ContraFect intends to use the capital to fundmedicines in access countries while demonstrating how it improves the availability and affordability

its R&D activities, including a Phase III candi-

of its medicines, including in low-income countries. For example, it can expand access to Zavicefta®
and Zinforo® in Sub-Saharan Africa while taking ability-to-pay into account.

date targeting S. aureus.
• In the last year, Pfizer acquired Arixa
Pharmaceuticals and Amplyx Pharmaceuticals,Inc., two companies focused on developing antibacterial and antifungal treatments,
respectively.

126

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONSPFZRevenue by business segment

Therapeutic areas: Hospital, Inflammation & immunology, Internal medi-

2019

cine, Oncology, Rare diseases, Vaccines

2020

Business segments: Biopharmaceutical products

39,09041,9080

Product categories: Biosimilars, Generic medicines, Innovative medicines,

10,00020,000Biopharmaceutical Products

Vaccines

2,082

30,00040,000Consumer Health

50,000mn USD

PFZ
Revenue by region

M&A since 2020: In July 2019, Pfizer and GSK combined their consumer
health care business into a joint venture, with Pfizer controlling an equity
interest of 32%. In November 2020, Pfizer spun its Upjohn Business2019

off to combine it with Mylan N.V. to form Viatris Inc. In October 2020,

2020

Pfizer acquired Arixa Pharmaceuticals, a company focused on develop-

20,5930

ing next-generation oral antibiotics for drug-resistant Gram-negative infec-

20,57921,712
10,000

United States

20,19620,00030,00040,000International

50,000mn USDtions. In April 2021, Pfizer acquired Amplyx Pharmaceuticals, Inc., including their lead drug fosmanogepix, a potentially first-in-class antifungal
treatment.
PIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 13 projects targeting pathogens in scope* (7 antibacterial

Comparatively large portfolio: At least 116 products: 98 antibacterial medi-

medicines; 5 antibacterial vaccines; 1 antifungal medicine).

cines; 4 antibacterial vaccines; 14 antifungal medicines

Development stages: 6 clinical projects, including a Phase III vaccine can-On-patent medicines: 5 (anidulafungin, ceftazidime/avibactam, ceftaroline,

didate for C. difficile infections and a Phase II clinical vaccine candidate forisavuconazole, tavaborole)

the prevention of group B Streptococcus infections; and 5 discovery/pre-On-patent vaccines: 4 (Trumenba®, NeisVac-C®, Nimenrix®, Prevnar 13®)clinical projects.

Off-patent/generic medicines: 10 of 107 were selected for analysis*

Novelty: 1 project, potential first-in-class Phase II antifungal: fosmanogepix.

(amoxicillin [A], azithromycin [W], chloramphenicol [A], ethambutol/isoni-‘Critical’ and/or ‘urgent’ pathogens: 7 projects, with the focus on resist-azid/pyrazinamide/rifampicin [T], ethambutol/isoniazid/rifampicin [T], flu-

ant Enterobacteriaceae, C. auris and C. difficile. Pfizer has a Phase III vac-conazole [F], minocycline [W], polymyxin b [R], tigecycline [R], voricona-cine candidate for C. difficile. Its Phase II antifungal fosmanogepix targets

zole [F])C. auris.

AWaRe medicines***: 26 Access group; 31 Watch group; 8 Reserve group

Regulatory approvals: 4 approvals. In September 2019, the FDA gave a

Anti-TB medicines***: 11

supplemental approval for ceftaroline fosamil (Teflaro®/Zinforo®)** toPFZPipeline for priority pathogens

treat Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in neonatal populations (from birth to less than 2 months of age). In June 2021, the
FDA approved Prevnar20™, a pneumococcal 20-valent conjugate vaccine
for adults. Avycaz®/Zavicefta®** received two label extensions by the EMA
in October 2020.

0

5

71

0

10

20

PFZ
Products on the market
98 14

PERFORMANCE BY RESEARCH AREA

0

20

40

60

80

100

A

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Investments in R&D

icines and/or vaccines for pathogens in scope.

Pfizer does not disclose publicly, or to the

Pfizer has pledged USD 100 mn to the AMR

Benchmark, its R&D investments during 2019

Action Fund over the next ten years.

and 2020 in antibacterial and antifungal med-120

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

A.2.1 Pfizer nearly doubles the size of its
pipeline
The company reports 13 projects targeting pathogens in scope: eight medicines and five vac-

Pipeline targeting priority pathogens: 13† As at 24 September 2021
Discovery

Pre-clinical

Phase I

Phase II

Phase III

Approval

Ceftazidime/avibactam(Avycaz®/Zavicefta®)**[Enterobacteriaceae, P.
aeruginosa] - additional
population: neonates♦ C. difficile vaccine (PF06425090)♦ S. pneumoniae
20-valent conjugate vaccine (Prevnar20™)[FDA/Jun-21]‡♦ Group B Streptococcus
vaccine (PF-06760805)
Fosmanogepix [C. auris]

Aztreonam/avibactam(PF-06947387) [Enterobacteriaceae]♦ S. pneumoniae
20-valent conjugate
vaccine (Prevnar20™)- additional population:
paediatricCeftaroline fosamil(Teflaro®/Zinforo®)**[S. aureus][FDA/Sep-19] additional
population: neonates♦ = Vaccine† Includes 5 conﬁdential projects not shown in the ﬁgure.
‡ Approved after the end of the period of analysis.

* See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.

** Avycaz® and Teflaro® are marketed byAllergan in the USA.
*** Listed on the 2019 WHO EML.

127

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundationcines. Twelve targeting bacterial pathogens anddevelopment include candidates targeting C. dif-

one targets fungal pathogens. Out of the 13 pro-ficile, group B Streptococcus and S. pneumoniae.

three in Phase III and two have obtained market-

jects, five are in discovery/preclinical stage, six

In June 2021 Prevnar20™, a 20-valent pneumo-

ing approval.

are in clinical development and two received

coccal vaccine was approved by the FDA. Pfizer

For seven out of eight of its projects in late-marketing approval.

is conducting Phase III trials to extend the use

stage development, Pfizer has ongoing clini-of this newly approved vaccine to paediatriccal trials or aims to file the successful products

populations.

in access countries§. The plans for this projects

A.2.2 Both innovative and adaptive medicine

include a wide range of access components suchclinical candidates
Pfizer’s clinical-stage medicine pipeline con-four of them are vaccines. Three are in Phase II,

A.2.4 Seven candidates targeting critical and/or urgent priorities

sists of both innovative and adaptive R&D pro-as filing for registration in access countries§,
equitable pricing and measures to strengthen

jects. Pfizer is working on extending the indications of ceftazidime/avibactam (Avycaz®/Pfizer has seven projects targeting pathogens

supply. Furthermore, its late-stage R&D med-

defined as ‘critical’ by WHO’s list of priority path-

icine projects are covered by portfolio-wide

Zavicefta®)** and ceftaroline fosamil (Teflaro®/

ogens and/or characterised as ‘urgent’ threats

stewardship plans, including initiatives for sur-

Zinforo®).** It is developing the combination ofby the US Centers for Disease Control andveillance (ATLAS) and research and education

aztreonam/avibactam (PF-06947387) against

Prevention (CDC). In clinical development, Pfizer

on AMR (via unrestricted grants). For its recently

MDR gram-negative infections. In April 2021,

has medicine candidates against Carbapenem-

acquired Phase II antifungal, fosmanogepix,

Pfizer acquired Amplyx Pharmaceuticals Inc andresistant/ESBL-producing E. coli and C. auris,

Pfizer plans to continue the Expanded Accessis now taking over the clinical development of its

and a vaccine candidate targeting C. difficile.

Programme that Amplyx Pharmaceuticals Inc

novel antifungal, fosmanogepix.

had in place.
A.3

A.2.3 Five vaccine candidates

Comprehensive planning for access andstewardship

Pfizer reports five vaccine projects in its pipeline.

Pfizer has eight late-stage R&D projects tar-

It includes three innovative and two adaptive

geting pathogens in scope, the highest number

projects. Pfizer’s vaccines in clinical stages ofacross all the R&D-based companies evaluated,B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Comprehensive environmental risk-man-tocols for preventing contamination. It also

agement for own sites and suppliers;

employs conservative measures for effluents

tracks compliance with limits at own

sent to external private and public wastewatersites

treatment plants.

from its own or suppliers’ sites.
B.3

System in place to maintain production
quality for own and suppliers’ sites; noPfizer reports a comprehensive strategy to min-requests for official corrective action
Publicly discloses some information on

Pfizer reports that its own sites and suppliers

and solid waste from antibacterial manufactur-

environmental risk management andhave a system to maintain high-quality antibac-

ing at its sites, including audits every three years.

commitment to set limits

terial production consistent with international

imise the environmental impact of wastewaters

B.2

It reports setting discharge limits in the receiv-

Pfizer publishes some components of its envi-

GMP standards. This includes periodic risk-

ing environment for all antibacterials manufac-

ronmental risk-management strategy. It is abased audits and tracking of corrective and pre-tured at its sites, based on PNECs to limit AMR,

member of the AMR Industry Alliance, which

ventive actions. Pfizer also requires its suppli-

as recommended by the AMR Industry Alliance.

publishes a list of recommended antibacterial

ers to audit their own suppliers. The Benchmark

Discharge levels are quantified at all sites using

discharge targets. Pfizer publishes its commit-

found no requests for official corrective actiona mass balance approach, verified by chemicalment to setting these targets. It also publicly

from the FDA or EMA related to non-conformi-

analysis if applicable. It reports that compliancediscloses that it is developing a, AMR Industry

ties with cGMP at Pfizer’s own sites or any sub-of own sites with discharge limits is tracked.

Alliance sponsored, consensus-based standard

sidiaries that manufacture antibacterials.

Pfizer requires third-party suppliers of anti-

to demonstrate responsible manufacturing ofbacterials to follow the same standards, includ-

antibiotics. Pfizer publicly discloses that >90%

ing limits based on PNECs. It reports conduct-of own sites are compliant with the guidelines ofing on-site audits at least every five years. It

the AMR Industry Alliance, and that >80% sup-requests and reviews the discharge levels of its

pliers are assessed against these guidelines. It is

suppliers. All supplier sites have quantified dis-

unclear whether such compliance also includes

charge levels.

compliance with discharge limits. Pfizer does not

Pfizer expects external private waste-treat-publish: (1) the results of environmental audits,ment plants to comply with its general environ-conducted at its own sites, the sites of suppliers

mental standards. It audits these plants every

and/or external private and public waste-treat-

3-6 years which includes the suitability of tech-ment plants; (2) a list of these suppliers andnologies used for processing waste and pro-plants; or (3) the levels of antibacterial discharge

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries§
C.1.1

Filed to register on-patent medicines ingal anidulafungin (Eraxis; Ecalta®) used to treat

14 access countries on averageinvasive candidiasis, filed in 22 access coun-registration in nine access countries.
C.1.2 Filed to register off-patent/generic med-

Pfizer performs above average, filing four oftries. Its reserve antibiotic, ceftazidime/avibac-

its five relevant on-patent medicines for regis-tam (Zavicefta®), was filed for registration in 20

tration in 14 access countries§ on average. Its

access countries, including three LICs. Its anti-

Pfizer performs above average, filing eight of ten

most widely filed relevant product is the antifun-

fungal isavuconazole (Cresemba®) was filed forrelevant off-patent/generic medicines for reg-** Avycaz® and Teflaro® are marketed byAllergan in the USA.
§ 102 low- and middle-income countries
where better access to medicine is mostneeded.

icines in 17 access countries on average

128

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

istration in 17 access countries on average. Itsfor all its reported approaches. It estimates to

It has set a six-tiered pricing policy for Prevnar

most widely filed relevant product is the antifun-

have ensured access to ceftaroline (Zinforo®)13®. The tiers are defined by several criteria

gal fluconazole, filed in 52 access countries. Six

ceftazidime/avibactam (Zavicefta™) and isavu-

such as countries’ GNI per capita. Pfizer partnersof its sample products are filed in less than 10

conazole (Cresemba®) for 51,000 cumulativewith Gavi to provide Pneumococcal Conjugate

access countries. Four of its sample products arepatients in low- and middle-income countries in

Vaccine (13-valent) (Prevnar 13®) to Gavi-eligible

filed for registration in at least one LIC.

2020.

and Gavi-transitioned countries at a public priceC.1.3 Filed to register on-patent vaccines in 24

C.2.2 Several strategies to expand access tovides evidence of patient reach and geographic

off-patent/generic medicinesreach for all its reported approaches. It commitsof USD 2.90 per dose until 2027. Pfizer proaccess countries on average
Pfizer has an average performance, filing three

Pfizer performs above average, with accessof its four relevant on-patent vaccines for regis-

strategies reported for four of its ten relevant

Conjugate Vaccine (13-valent) (Prevnar 13®) bytration in access countries. Its most widely filed

off-patent/generic medicines. It aims to expand

2027 through its partnership with Gavi.

relevant vaccine is the Pneumococcal Conjugate

access in low- and middle-income countries

Vaccine (13-valent) (Prevnar 13®) filed in 65

through donations and public/private partner-

access countries. Prevnar 13® is followed by theships. It provides evidence of patient and geo-meningococcal vaccine Nimenrix® , filed for reg-graphic reach for all its reported approaches.

Pfizer performs above average, with strategies

istration in 23 access countries, including LICs.

Pfizer takes part in the International Trachoma

reported in all four areas assessed. Pfizer ensures

Initiative (ITI) and donated 31 mn azithromycin

accurate demand planning and data analytics bytreatments to 12 countries in 2020. It extended

forecasting on a monthly and 24-month rollingits donation programme until 2025. Through its

basis. Pfizer mitigates against shortage risks by

Pfizer performs above average, with access

Diflucan® Partnership Program, Pfizer distrib-

keeping buffer stocks for its finished products at

strategies reported for three of five relevant

uted 7mn doses of fluconazole to nine accesscountry-level, for APIs at a global-level, and manu-

on-patent medicines. It aims to expand accesscountries through governments and NGOs in

factures some of its APIs in-house. Pfizer reports

to its on-patent medicines in access countries

2019 and 2020.

one technology transfer initiative. Since 2014, it

C.2.1 Several strategies to expand access to
on-patent medicines

through equitable pricing policies, one priceper patient capitation model, and patient assis-

to supply 930 mn doses of its Pneumococcal

C.3

Several strategies to ensure continuous
supplyhas engaged in a public/private partnership in
C.2.3 Several strategies to expand access to
on-patent vaccines

tance programmes. To set the prices of ceftazi-South Africa to enable a local partner to manufacture Pneumococcal Conjugate Vaccine (13-dime/avibactam (Zavicefta™) and isavucona-

Pfizer performs above average, with accessvalent) (Prevnar 13®). To mitigate against sub-zole (Cresemba®), Pfizer takes into account local

strategies reported for one of its four relevant

standard and falsified products, Pfizer maintains

economic conditions, the average income, andon-patent vaccines. It aims to expand access ina Disruption Programme which identifies and dis-

GDP growth. It allows for net price flexibility foraccess countries through equitable tiered pric-

rupts online illicit sales. Pfizer uses serialisation

specific procurement requests. Pfizer provides

ing, public/private partnerships, humanitar-with unique products identifiers and has a public

evidence of patient reach and geographic reachian emergency assistance settings and tenders.

counterfeit awareness page.

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

and/or include treatment guidelines for health-in place for its educational programmescare professionals: for all antibacterial medicines

C.7

Active in multiple AMR surveillance programmes; one openly shares raw data

Pfizer performs strongly in conflict of interestand isavuconazole (Cresemba®), by using data

Pfizer leads in this area. It is active in multiple(COI) mitigation for the five AMR-related edu-from its ATLAS surveillance programme in the

AMR surveillance programmes. It runs the multi-

cational programmes for HCPs assessed by thematerials.

national ATLAS programme, which is focused on

Benchmark. To mitigate COI for all five pro-resistance against its antibacterial and antifunMakes three types of brochure and/gal medicines in 81 countries and has been run-pendent third parties (BSAC, the University ofor packaging adaptations to facilitatening since 2004. Pfizer shares the raw data on

Dundee, EBRD, ISID and Micron) to develop theappropriate use by patientsthe AMR Register, an open-access data platform,

grammes, it provides financial resources to inde-

C.6

Pfizer adapts packaging to facilitate the appro-

as well as the aggregated results on the ATLAS

priate use of azithromycin (Zithromax®) bywebsite and through peer-reviewed open-accessEngages in sales and marketing practices

patients. Pfizer performs strongly in this meas-

journal articles. For the remaining programmes,

to address appropriate useure, taking account of adherence to treatment,

only the aggregated results are shared throughPfizer performs above average in sales practices.

paediatric use and language. It adapts the pack-peer-reviewed open-access journal articles,

It reports that it partly decouples incentives foraging of azithromycin, named the Z-Pak, which

as well as on open-access data platforms forsales agents from sales volumes of its antibac-

facilitates patient adherence by organising

the SENTRY programme (an antifungal resist-terial and/or antifungal medicines. Its percent-the pill intake for each day, so that the patientance programme managed by JMI laboratories)

age of variable pay is capped at 30% and sales

knows exactly which pill(s) to take on which day

and the CANWARD programme (a national pro-targets are set at the national level. Its incen-

until the Z-Pak is completed. Moreover, Pfizer

gramme managed by the Canadian Antimicrobial

tives for sales agents in emerging markets inincludes a QR code on the packaging of azithro-

Resistance Alliance).

Asia are provided on the basis of confidentiality.

mycin as an oral suspension that directs patients

However, Pfizer does not reward its sales agentsto a video explaining how to administer the oral

based on antibacterial volumes sold in the UK.

suspension properly for adults and children. This

Pfizer engages in marketing practices thatis applied in Vietnam and the Philippines and theaim to address the appropriate use of its anti-

video will be played in the local language. Finally,

bacterial and/or antifungal medicines consist-

Pfizer has translated instructions on the packag-

ent with the approved indication. Its market-

ing to the local language in Japan.

programme.
C.5

ing materials reflect emerging resistance trends

129Antimicrobial Resistance Benchmark 2021

SNF

Overall Performance
2020

2021

42% 60%▲Access to Medicine Foundation

Sanofi
Large R&D-based pharmaceutical company
Stock exchange: EPA • Ticker: SAN • HQ: Paris, France • Employees: 99,412

SNF
PERFORMANCE
Sanofi performs average overall in its evaluated Research Areas

Performance in the Benchmark

0%compared to the other large research-based pharmaceutical companies
in scope.
R&D: Sanofi performs less well in the R&D Research Area. Its six-projectpipeline has three vaccines and three medicines. No project targets
critical and/or urgent pathogens. Sanofi has four projects in late-stage
development for which it reports having access plans.
Responsible Manufacturing: Performs well. Reports environmental risk-

Appropriate Access: Performs strongly. Files its on-and off-patent

Stewardship: Middle-performing. It does not promote antibacterial and/or antifungal medicines to healthcare professionals outside France.
It supports a surveillance programme in France of which aggregatedresults are publicly shared. It reports comprehensive conflict of interest
mitigation for its educational programme. It does not adapt brochures or

50%

100%

Points33%

R&D

10/ 3073%

Manufacturing

11/ 1584%

Access21/ 2560%

Stewardship0%

12/ 2050%

100%

How Sanofi was evaluatedproducts for registration in access countries. Reports several strategies
to expand access and ensure continuous supply of its relevant products.

/ 90
54/

Performance by Research Area

management strategy for own sites and suppliers; quantifies discharge
levels at all own sites

Points60%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

packaging for patients.
● ● ● Scored●

Not scored

OPPORTUNITIES FOR SANOFICHANGES SINCE 2020

Expand breadth of R&D pipeline into more pathogens. Sanofi has antibacterial vaccines and med-

• Since 2020, Sanofi reports requesting its sup-icines in late-stage clinical development that target, e.g., S. pneumonia and M. tuberculosis. Sanofi

pliers to conduct risk assessments according

can expand the focus of its pipeline to target resistant pathogens for which R&D is limited, such as

to the guidelines of the AMR Industry AllianceCampylobacter spp. and H. pylori. It can do so by investing in in-house R&D, through acquisition or

including quantification of discharge levels

collaboration with other companies, or by joining existing public private partnerships.
Expand and tailor access and stewardship plans for late-stage R&D projects. Sanofi has both vac-against limits.
• In November 2019, Sanofi and Cyclamedcines and medicines in late-stage clinical development. It can improve access to these new prod-

launched the AnTRIbiotics campaign, whichucts, by developing plans for registration, affordability and sustainable supply. For example, for theirencourages the general public to bring expired

phase II vaccine, Skypac, Sanofi can develop equitable pricing plans that consider ability-to-pay andor unused antibiotics back to the pharmacy.

apply supply chain best practices including buffer and safety stocks and shortage mitigation strategies. In addition, Sanofi can expand its stewardship plans for its medicine R&D projects by getting
involved in comprehensive surveillance activities resistance trends information to their products aswell as other medicines often given alongside them in the long multidrug treatments required forthis disease, and to do it in relevant geographical regions where limited evidence is available.
Ensure compliance with antibacterial discharge limits at suppliers’ sites by tracking and publicly
disclosing progress and results specific to antibacterials for all sites. Sanofi can quantify discharge
levels at all suppliers’ sites and track compliance with set limits, as it does at own sites, and publicly
disclose the results. To provide clear evidence of its progress it can publicly report compliance at allsites. Disclosure of information, including the results of audits and antibacterial discharge levels of
its own sites and suppliers’ sites, is important. It can also publicly disclose the names and locationsof its suppliers and waste-treatment plants for increased transparency.
Expand registration of antibacterial and antifungal medicines. Sanofi can expand filing for registration of its off-patent antibiotics and antifungals listed on the 2021 WHO EML, such as colistin
and fosfomycin, to more countries, including low-income countries, with a high burden of disease.
Publicly share raw data from surveillance programme. Sanofi supports a national programme
focused on S. pneumoniae, the Observatoires Régionaux du Pneumocoque (ORP) programme,
managed by the National Reference Centre for Pneumococci (NRCP). Either Sanofi or the NRCP
can publicly share raw data from this surveillance programme.

130

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

SNFNet sales by business segment

Therapeutic areas: Cardiovascular diseases, Diabetes, Infectious diseases,

2019

Inflammatory & immune diseases, Oncology, Rare Diseases & Rare Blood

2020

disorders, Neurology.

0Business segments: Pharmaceuticals, Vaccines, Consumer healthcare
Product categories: Consumer health products, Generic medicines,
Innovative medicines, Vaccines
M&A since 2020: None in the antibacterial and/or antifungal sectors

10,000

Pharmaceuticals

25,7005,731 4,695

25,674

5,973 4,394

20,000

Vaccines

30,00040,00050,000mn EUR

40,00050,000mn EUR

Consumer Healthcare

SNF
Net sales by region
201912,756

9,082

14,2882020

13,465

9,151

13,425

10,00020,0000
United States

Europe30,000Rest of world

PIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 6 projects targeting pathogens in scope* (3 antibacterialMid-sized portfolio: At least 47 products: 33 antibacterial medicines; 11

medicines; 3 antibacterial vaccines).

antibacterial vaccines; 3 antifungal medicines

Development stages: 4 clinical projects, including the Phase II pneumo-

On-patent vaccines: 3 (Hexaxim®, Menactra®, Shan5™)

coccal conjugate vaccine (Skypac) candidate; and Shan6™, a Phase III hex-

Off-patent/generic medicines: 10 of 44 were selected for analysis* (amox-

avalent vaccine targeting among others H. influenzae and B. pertussis, for

icillin [A], cefotaxime [W], ceftriaxone [W], clotrimazole [F], colistin [R],which Sanofi has already obtained marketing authorisation.

Fosfomycin [R], isoniazid [T], metronidazole [A], nystatin [F], rifampicin

Novelty: 0 novel clinical-stage medicine projects.

[T])‘Critical’ and/or ‘urgent’ pathogens: 0 projects targeting ‘critical’ and/or

AWaRe medicines**: 7 Access group; 14 Watch group; 2 Reserve group‘urgent’ pathogens.

Anti-TB medicines**: 7Regulatory approvals: 1 approval. In May 2021 the Indian regulatory authorities approved Shan6™, a paediatric hexavalent vaccine targeting H. influ-

SNF
Pipeline for priority pathogens

enzae and B. pertussis.

3

3

0

10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

SNF
Products on the market
11
0

33 3
20

40

60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Investments in R&D

A.2.1 Small pipeline

for antituberculosis medicines. A new water

Sanofi reports to the Benchmark the amountThe company reports six projects targeting

dispersible formulation of rifapentine/isonia-

invested during 2019 and 2020 in R&D for anti-

pathogens in scope: three medicines and three

zid for improved dosing in latent tuberculosis inbacterial and antifungal medicines and/or vac-vaccines, all targeting bacterial pathogens. Out

children is in Phase II. In Phase III, rifapentine iscines for pathogens in scope. Specific invest-of the six projects, three are in clinical develop-

included in a trial aiming at optimising the treat-ment figures were provided under confiden-

ment and one received marketing approval.

ment of latent and active tuberculosis with atiality. As a proportion of its revenues, Sanofi

shorter and simpler dosing regimen.

reports lower R&D investments than other

A.2.2 No clinical-stage novel projects

companies assessed in this indicator. In abso-

Sanofi’s clinical-stage medicine pipeline con-A.2.3 Three vaccine candidates

lute terms, however, the amount it invests is thesists of two adaptive projects developing for-

Sanofi reports three vaccine projects in its pipe-

second largest.

mulations and optimising treatment regimens

line. It includes one innovative candidate in

Pipeline targeting priority pathogens: 6*** As at 24 September 2021
Discovery

Pre-clinical

Phase I

Phase II

Phase III

Approval♦ S. pneumonia (conjugate) vaccine (Skypac)

Rifapentine - New regimen: shorter treatment[M. tuberculosis]♦ Pediatric hexavalentvaccine DTP-HepB-Polio-Hib (Shan6™) [H.
influenzae, B. pertussis] [Indian regulatory
authorities/May-21]

Rifapentine/isoniazid additional formulation:
fixed-dose water-dispersible tablet for paediatric patients [M. tuberculosis]♦ Vaccine
DTP = Diphtheria, tetanus and pertussis
HepB = Hepatitis B
Hib = Haemophilus influenzae type B*** Includes 2 projects not shown in the ﬁgure: 1 project intechnical lifecycle and 1 project in Phase IV.

* See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
** Listed on the 2019 WHO EML.

131

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

Phase II of clinical development targeting S.

by WHO’s list of priority pathogens and/or char-tries† for three out of its four late-stage pro-pneumoniae (Skypac), and an adaptive vaccine

acterised as ‘urgent’ threats by the US Centersjects. Sanofi plans to apply for WHO prequali-

candidate targeting H. influenzae and B. pertus-

for Disease Control and Prevention (CDC).

fication for both of its vaccine projects (paedi-

sis: Shan6™.

atric DTP-HepB-Polio-Hib hexavalent vaccine
A.3

A.2.4 No candidates targeting critical and/or
urgent priorities

Access plans for late-stage projects

Shan6™, and pneumococcal conjugate vaccine

Sanofi has four projects in late-stage devel-

Skypac) to ensure access in GAVI-eligible coun-

opment: two tuberculosis medicines and twotries. Sanofi does not report stewardship activ-

Sanofi does not have any candidates in its R&D

vaccines.

ities for its late-stage antituberculosis medicine

pipeline targeting pathogens defined as ‘critical’

Sanofi has ongoing clinical trials in access coun-projects.

B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Environmental risk-management for own

ments it makes of external private waste-treat-

terial discharge from its own or suppliers’ sites

sites and suppliers; tracks compliancement plants. It does report auditing these plantsthat manufacture antibacterials.

with limits at own sites

which includes checking the suitability of tech-

Sanofi reports a strategy to minimise the envi-

nologies used for processing waste. It alsoronmental impact of wastewaters and solid

reports employing conservative measures for

waste from antibacterial manufacturing at

effluents sent to external private and public

its sites, including audits every three years. It

wastewater plants.

reports setting discharge limits in the receiv-

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

Sanofi reports that its own sites and suppliers
have a system to maintain high-quality antibac-

Publicly discloses some information on

terial production consistent with international

tured at its sites, based on PNECs to limit AMR,

environmental risk management and

GMP standards. This includes periodic risk-

as recommended by the AMR Industry Alliance.

commitment to setting limits

based audits and tracking of corrective and pre-ing environment for all antibacterials manufac-

B.2

Discharge levels are quantified at all sites using

Sanofi publishes some components of its envi-

ventive actions. Sanofi also requires its suppli-a mass balance approach, verified by chemicalronmental risk-management strategy. It is a

ers to audit their own suppliers. The Benchmark

analysis if applicable. It reports that compliancemember of the AMR Industry Alliance, whichfound no requests for official corrective actionof own sites with discharge limits is tracked.

publishes a list of recommended antibacte-from the FDA or EMA related to non-conformi-

rial discharge targets. Sanofi publishes its com-ties with cGMP at Sanofi’s own sites or any sub-bacterials APIs and drug products to follow sim-

mitment to setting these targets and assess-sidiaries that manufacture antibacterials.

ilar standards, including limits based on PNECs.

ing pharmaceutical levels in wastewaters. It pub-

It reports conducting on-site audits every 1-5

lishes information on the progress towards its

years. It also requests and reviews the discharge

risk-management strategy for pharmaceuti-

levels of its suppliers. It reports 103 of 117 sup-cals in the environment and HSE audits for pri-pliers’ sites, or 88% have been audited on vari-ority suppliers (including antibacterial suppliers).

ous HSE topics including AMR. As part of such

Sanofi does not publish: (1) the results of envi-

audits, suppliers are asked whether they haveronmental audits, conducted at its own sites, thequantified discharge levels but it is unclear how

sites of suppliers and/or external private andmany suppliers have done so.

public waste-treatment plants; (2) a list of these

Sanofi requires third-party suppliers of anti-

There is limited information on the require-C

suppliers and plants; or (3) the levels of antibac-

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries†
Sanofi is not eligible for indicators: C.1.1 and C.2.1.

Hexaxim® is followed by the meningococcal con-prices up to 45% lower than those offered in the

For more information, see Appendix VII.

jugate vaccine Menactra®, filed in 48 countries.

private sector.

Sanofi filed all its three relevant on-patent vacC.1.2 Filed to register off-patent/generic med-cines for registration in at least one LIC.

C.2.3 Several strategies to expand access to

C.2.2 Several strategies to expand access to

Sanofi performs above average, with accessoff-patent/generic medicines for registration in

off-patent/generic medicines

strategies reported for all its three relevant

access countries. Its most widely filed relevant

Sanofi performs above average, with accesson-patent vaccines. It expands access in accessproduct is the antifungal metronidazole, filed instrategies reported for five of its 10 relevant

countries through equitable pricing, tenders

48 access countries. Five of its relevant products

off-patent/generic medicines. It expands accessand public or private partnerships. Sanofi has a

are filed in less than ten access countries. Fourto its off-patent/generic medicines in accesstiered pricing policy where price is defined byof its relevant products are filed for registration

countries through a voluntary licensing agree-

the channel of distribution and countries’ GNI

in at least one LIC.

ment, donations and tenders. In 2020, Sanofi

per capita. It partners with UNICEF to provide

coordinated the donation of 9,300 packs of

Shan5™ at a defined price. Sanofi provides evi-

metronidazole for emergency kits preparation

dence of patient reach and geographic reach forand 55,000 packs of amoxicillin in Colombia. In

some of its reported approaches. In 2020, it esti-

Sanofi performs above average, filing all its three

2020, it supplied more than 9 mn packs of iso-mates to have reached more than 5 mn people

relevant on-patent vaccines for registration inniazid and more than 1.2 mn packs of rifampicin

worldwide with Hexaxim®.

access countries. Its most widely filed relevant

containing regimens through a government

vaccine is Hexaxim®, filed in 54 access countries.

tender for tuberculosis in South Africa, withicines in 13 access countries on average
Sanofi performs above average, filing all its 10

C.1.3 Filed to register on-patent vaccines in 40
access countries on average† 102 low- and middle-income countries
where better access to medicine is mostneeded.

on-patent vaccines132

Antimicrobial Resistance Benchmark 2021

C.3

Access to Medicine Foundation

Several strategies to ensure continuous

Sanofi reports four capacity building or tech-supplynology transfer initiatives, in India, Nigeria andSanofi performs above average, with strate-

Vietnam. To mitigate against substandard andgies reported in all four areas assessed. Sanofi

falsified products, Sanofi has an anti-counterfeit-

ensures accurate demand planning and data

ing coordination network, a security department

sharing by having a monthly process for supply

to detect online illicit sales and a central labora-

planning with a 36-month time horizon. Sanofi

tory of counterfeit analysis.

has a “zero out-of-stock” objective with shortterm (up to 36 months) and long-term (36months to 5-10 years) forecasts. Sanofi mitigates against shortage risks by keeping buffer
stocks. It produces some of its APIs in-houseand ensures dual sourcing for all other APIs.

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

reports that it partly decouples incentives forin place for its educational programmesales agents from sales volumes of this product.

C.7

Active in one AMR surveillance programme; openly publishes aggregatedresults

Sanofi performs strongly in conflict of inter-

Sanofi engages in marketing practices thatest (COI) mitigation for the one AMR-related

aim to address the appropriate use of its anti-

Sanofi funds a national programme managed byeducational programme for HCPs assessedbacterial and/or antifungal medicines. Its mar-the National Reference Centre for Pneumococciby the Benchmark. The programme has all

keting materials reflect emerging resistance(NRCP) with the French Regional Pneumococcal

three COI mitigation strategies looked for bytrends and/or include treatment guidelines

Observatories. It is focused on S. pneumoniae

the Benchmark: (1) content is developed inde-for healthcare professionals: for pristinamycin

in France and has been running since 2000.

pendently from its marketing department; (2)(Pyostacine®).

Only the aggregated results are shared by NRCP

participants are not provided financial or material incentives (as it is a website); and (3) a policyof not using branded materials.

through peer-reviewed open-access journal
C.6

Does not report adapting brochures and/articles.

or packaging to facilitate appropriate
use by patients

C.5

Engages in sales and marketing practices

Sanofi does not report adapting brochures and/to address appropriate useor packaging to facilitate the appropriate use of

Sanofi performs above average in sales prac-

its antibacterial and/or antifungal medicines bytices. It does not deploy any sales agents to pro-patients.

mote its antibacterial and/or antifungal medicines to healthcare professionals outside ofFrance. However, for its sales in France, which
are only for pristinamycin (Pyostacine®), Sanofi

133Antimicrobial Resistance Benchmark 2021

SNG

Overall Performance
2020

2021

63% 58%▼

Access to Medicine Foundation

Shionogi & Co, Ltd
Large R&D-based pharmaceutical company
Stock exchange: TSE • Ticker: 4507 • HQ: Osaka, Japan • Employees: 5,233

SNG
PERFORMANCE
Shionogi performs average overall in its evaluated Research Areas

Performance in the Benchmark

0%compared to the other large research-based pharmaceutical companies
in scope.
R&D: Shionogi performs well in R&D. Eight of its 11 projects target
critical and/or urgent pathogens. For the first time Shionogi has a
vaccine in their pipeline. Shionogi is working on improving access andstewardship of its antibacterial cefiderocol.
Responsible Manufacturing: Shionogi leads. Reports comprehensiveof strategy and compliance

Stewardship: Performs well. It fully decouples incentives for sales
agents from sales volumes. It publicly shares aggregated results of its
surveillance programmes. It reports comprehensive conflict of interest
mitigation for its educational programmes. It adapts brochures forpatients.

50%

100%

Points70%

R&D

21/ 3093%

Manufacturing

14/ 15

4%

Access

1/ 25

80%

Stewardship
0%50%

16/ 20100%

How Shionogi was evaluatedAppropriate Access: Performs low. Its relevant on- and off-patentproducts are not available in access countries.

/ 90
52/

Performance by Research Area

environmental risk-management strategy for own sites and suppliers;
co-leads in compliance with limits at own sites; leads in public disclosure

Points58%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR SHIONOGICHANGES SINCE 2020

Expand breadth of R&D pipeline and depth of R&D access and stewardship plans. Shionogi• In response to an opportunity from the 2020

has one of the most diverse pipelines across all large research-based companies in the AMR

AMR Benchmark, in July 2021, Shionogi

Benchmark. It can expand the focus of its pipeline to target resistant pathogens for which R&D isentered into a collaboration with the Global

limited, such as Campylobacter spp. and H. pylori. For its recently approved cefiderocol (Fetroja®/

Antibiotic Research and Development

Fetcroja®), Shionogi engages with generic medicines manufacturers and access-related organisa-

Partnership (GARDP) and the Clinton

tions such as GARDP and the Clinton Health Access Initiative to increase affordability and availabil-

Health Access Initiative (CHAI) to accelerate

ity. Shionogi can intensify these engagements to reach more patients and countries. Shionogi canaccess, including in LMICs, to the antibiotic

continue to build towards a comprehensive surveillance programme to ensure cefiderocol is not
used excessively.

cefiderocol.
• In October 2020, Shionogi expanded invest-

Expand registration to cefiderocol (Fetroja®/ Fetcroja®) in access countries. Shionogi can file cefi-

ments into vaccine development through aderocol (Fetroja®/ Fetcroja®) for registration in access countries. Further, to accelerate the availabil-licensing partnership agreement with HanaVax

ity of cefiderocol in access countries Shionogi can consider voluntary non-exclusive licensing, com-

for research, development, manufacturing, dis-passionate use programmes and public/private partnerships.

tribution and commercialisation of their S.

Expand adaptations to brochures and packaging to consider more patient needs. Shionogi adapts
brochures to take account of paediatric use to support the appropriate use of cefcapene pivoxil

pneumoniae nasal vaccine candidate.
• In its 2020 Environmental Report, Shionogi(Flomox®) by patients. It can further adapt its brochures and packaging of all antibacterial and anti-

discloses compliance with limits of its own andfungal medicines to consider local languages, literacy levels, environmental conditions and patient

suppliers’ sites, some details of audit results

adherence to treatment.

and some names and/or locations of its suppli-

Publicly share raw data from surveillance programmes. Shionogi runs the multinational
SIDERO-WT programme, which is focused on resistance against antibacterials targeting Gram-ers and sole waste contractor.
• In 2020, Shionogi started to support thenegative bacteria. It can publicly share raw data from this surveillance programme, following

SENTRY programme for the surveillance ofthrough on commitments to share this with the AMR Register in 2021. Additionally, either Shionogi

cefiderocol. The results are shared publicly via

or the managing partners should publicly share raw data from the other surveillance programmes it

open-access journal articles and the SENTRY

is involved in.

website.

134

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

SNGRevenue by business segment

Therapeutic areas: Infectious diseases, Psycho-neurological diseases

2019

Business segments: Prescription drugs

2020

Product categories: Generic medicines, Innovative medicines, Vaccines

An Shionogi Company Ltd

297,177
0

M&A since 2020: In July 2020, Shionogi entered into agreement with Ping
An Life Insurance of China, Ltd. to establish of a joint venture called Ping

333,371

100,000

200,000

300,000

400,000

Prescription drugs

500,000
mn JPY

SNG
Revenue by region
109

2019
95

2020
0
Japan

31
25

100

200
bn JPY

Rest of world

PIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 11 projects targeting pathogens in scope* (8 antibacterial

Comparatively small portfolio: At least 8 products: 8 antibacterial

medicines; 1 antibacterial vaccine; 2 antifungal medicines).

medicines

Development stages: 5 discovery programmes for antifungals, antituber-On-patent medicine: 1 (cefiderocol)

culosis and antibacterial candidates; 2 preclinical projects including an anti-

Off-patent/generic medicines: 7 of which 2 were selected for analysis*

body against P. aeruginosa and a vaccine for S. pneumoniae; and 1 Phase II(cefcapene [W], flomoxef [W])adaptive project.

AWaRe medicines**: 2 Access group; 5 Watch group

Novelty: 0 novel clinical-stage medicine projects.
‘Critical’ and/or ‘urgent’ pathogens: 8 projects, cefiderocol (Fetroja®/
Fetcroja®) and its adaptations target CRAB, CRE and CRPA. Furthermore,
Shionogi has discovery/preclinical projects targeting C. auris and P.
aeruginosa.
Regulatory approvals: 3 approvals. In November 2019, cefiderocol (Fetroja®/Fetcroja®) was approved by the FDA for the treatmentof complicated urinary tract infections (cUTIs), including pyelonephri-

SNG
Pipeline for priority pathogens
01
0rial pneumonia (HABP/VABP). In April 2020 the EMA approved cefider-

2
10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

SNG
Products on the market

tis. In September 2020, the FDA approved the supplemental indication
for the treatment of hospital-acquired and ventilator-associated bacte-

8

8
0

10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

ocol (Fetroja®/Fetcroja®) for the treatment of gram-negative bacterial
infections.

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Highest relative investment in R&D

invested USD 74.22 mn in R&D for antibacterial

other companies who reported investments toShionogi discloses to the Benchmark its R&D

and antifungal medicines and vaccines in 2019

the Benchmark.. Shionogi has pledged USD 20

investments during 2019 and 2020 in antibac-

and 2020. Shionogi invests the highest propor-

mn to the AMR Action Fund over the next ten

terial and antifungal medicines and/or vaccinestion of its revenues in R&D in this area and theyears.

for pathogens in scope. Shionogi reports that it

third highest absolute amount compared to the

Pipeline targeting priority pathogens: 11 As at 24 September 2021
Discovery

Pre-clinical

Antituberculosis
programme 1

Antibody [P. aeruginosa]

Antituberculosis
programme 2♦ S. pneumoniae vaccine

Antifungal
programme 1
Antifungal
programme 2
Antibacterial
programme 3* See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
** Listed on the 2019 WHO EML.

Phase I

Phase II
Fetroja®/Fetcroja® additional population:
paediatricPhase III

ApprovalCefiderocol (Fetroja®/
Fetcroja®)[FDA; Nov-19] cUTI
[Enterobacteriaceae][EMA; Apr-20]
Gram-negative bacterial
infections[FDA; Sep-20] HABP/
VABP [Enterobacteriaceae]♦ Vaccine
cUTI = Complicated urinary tract infection
HABP = Hospital-acquired bacterial pneumonia
VABP = Ventilator-associated bacterial pneumonia

135

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

A.2.1 Medium-sized diverse pipeline

the extension of its indication to treat children.

The company reports 11 projects targeting path-

Cefiderocol does not meet any of WHO’s innova-

ogens in scope: ten medicines and one vaccine,

tiveness criteria.

nine targeting bacterial pathogens and two tar-

A.3

Plans to improve access and stewardshipfor cefiderocol

Shionogi has four projects in its late-stage pipeline, all related to different indications of thegeting fungal pathogens. Out of the 11 projects,

A.2.3 Newly active in vaccine development

same compound, cefiderocol, first marketed infive are in discovery stage, two are in preclinical

Shionogi reports one innovative vaccine projectDecember 2019.

development, one is in clinical development andin its pipeline. It consists of a preclinical vaccine

Shionogi reports having an ongoing Global

three received marketing approval during thecandidate against S. pneumoniae developed inCompassionate Use programme for cefidero-

period of analysis.

collaboration with HanaVax Inc.

col. It is discussing a potential technology trans-

A.2.2 No clinical-stage novel projects

A.2.4 Investing in early stage programmes tar-fer agreement with generic medicine manufacgeting critical and/or urgent priorities

Shionogi’s clinical-stage medicine pipeline con-turers to extend access to cefiderocol to other
territories. It is also building partnerships withsists of one innovative R&D medicine, cefider-

Shionogi has eight projects targeting pathogens

not-for-profit organisations to build a systemocol, a siderophore cephalosporin antibacterial

defined as ‘critical’ by WHO’s list of priority path-to support stewardship of cefiderocol. Shionogi

for the treatment of multi-drug resistant infec-

ogens and/or characterised as ‘urgent’ threats

reports plans to conduct surveillance of cefider-tions. Cefiderocol (Fetroja®/ Fetcroja®) obtainedby the US Centers for Disease Control andocol. Shionogi applied for the inclusion of cefi-

marketing approval for the treatment of com-

Prevention (CDC). Cefiderocol, which accounts

derocol in the WHO’s EML and suggested includ-plicated urinary tract infections (cUTIs), includ-for four of these projects, targets several MDR

ing it in the Reserve (AWARE) category.

ing pyelonephritis, from the FDA in November

gram-negative pathogens such as A. bauma-

2019, and for HABP/VABP in September 2020.

nii and Carbapenem-resistant/ESBL-resistant

In April 2020, it received approval from theEnterobacteriaceae. Shionogi is carrying out

EMA for the indication of gram-negative bacte-

several discovery and preclinical programmes

rial infections. Cefiderocol is in Phase II trials fortargeting P. aeruginosa and C. auris.

B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Comprehensive environmental risk-management for own sites and suppliers;

Shionogi expects its only external private

flomoxef (Flumarin®), doripenem (Doribax®) andsulfamethoxazole/trimethoprim (Bakuta®), aretracks compliance with limits at own

waste-treatment plant to comply with its gen-compliant with discharge limits. It also publishes

sites and supplierseral environmental standards. It audits this planta table listing its antibacterials in scope, their

Shionogi reports a comprehensive strategy toevery year which includes the suitability of tech-connection to own sites and suppliers, and which

minimise the environmental impact of waste-nologies used for processing waste and pro-are compliant with discharge limits. Further, itwaters and solid waste from antibacterial man-tocols for preventing contamination. All solid

publishes where five of its suppliers in scope

ufacturing at its sites, including audits every fivewaste and wastewater sent to this plant is set toare located (Japan and India) and the respective

years. It reports setting discharge limits in the

be incinerated.

products supplied by each. The name of its only

limits.

external private waste-treatment plant in scope

receiving environment for all antibacterials manufactured at its site, based on PNECs to limit
AMR, as recommended by the AMR Industry
Alliance, or the EMA. It also reports quantify-

B.2

Publicly discloses information on envi-

is also disclosed.

ronmental risk management; aggregatedaudit results and compliance with limits

B.3

System in place to maintain production
quality for own and suppliers’ sites; noing discharge levels at its site using a mass bal-

Shionogi leads in public disclosure of its envi-

ance approach, verified by chemical analysis ifronmental risk-management strategy. It pub-requests for official corrective action

applicable. Its sole manufacturing site in scope

lishes some information on audit results, based

Shionogi reports that its own sites and suppliers

is reported to be fully compliant with discharge

on its ERM strategy, and covers wastewater

have a system to maintain high-quality antibac-

limits.

management, solid waste management and dis-terial production consistent with international

Shionogi requires third-party suppliers ofcharge limits. It is a member of the AMR Industry

GMP standards. This includes periodic risk-

antibacterials to follow the same standards,

Alliance, which publishes a list of recommended

based audits and tracking of corrective and pre-including limits based on PNECs. It reports

antibacterial discharge targets. It publicly dis-

ventive actions. Shionogi also requires its suppli-

conducting on-site audits every five years. It

closes that all 5 antibacterials manufactured at

ers to audit their own suppliers. The Benchmark

requests and reviews the discharge levels of its

its own site are compliant with discharge limits.

found no requests for official corrective action

suppliers. It also reports five out of nine supplier

In addition, it is publicly disclosed that five out

from the FDA or EMA related to non-conform-sites have quantified discharge levels and three,of nine supplier sites have quantified discharge

ities with cGMP at Shionogi’s own sites or any

or 33%, of those are compliant with discharge

levels and three, or 33%, of those, which supply

subsidiaries that manufacture antibacterials.

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Shionogi is not eligible for indicators: C.1.3 andnegative bacteria when there are few treatment

treat several bacterial infections, in one accessC.2.3. For more information, see Appendix VII.

options available. It was approved by the FDA in

country (China).

2019 . Cefiderocol is newly included in the WHO
C.1.1

No filings for relevant on-patent

22nd EML (2021) as a ‘Reserve’ group antibiotic

medicines

effective against multi-drug resistant bacteria.

Shionogi’s performance is low as it has not yet
filed its relevant on-patent medicine in accesscountries. Its relevant on-patent medicine is

C.1.2 Limited filings for relevant off-patent
medicines

the antibiotic cefiderocol (Fetroja®/Fetcroja®),

Shionogi’s performance is low. It filed its off-pat-

used to treat infections caused by aerobic Gram-ent antibiotics flomoxef and cefcapene, used to*** 102 low- and middle-income countries where better access to medicine ismost needed.

136

Antimicrobial Resistance Benchmark 2021

C.2.1 No access strategy for relevant on-pat-

Access to Medicine Foundation

C.2.2 Expanding access to off-patent/genericent medicine

medicines

in July 2021, GARDP identified flomoxef as apotential treatment option for neonatal sepsis.

Shionogi’s performance is low as it does not

Shionogi’s performance is low as it does notreport strategies to expand access to its relevant

provide access to its two relevant off-patent/

C.3

on-patent medicine in access countries during

generic antibacterial medicines, flomoxef andShionogi’s performance is low as it does not yet

the period of analysis. However, in July 2021,

cefcapene, in access countries. These two med-

make its relevant products available in access

Shionogi, GARDP and CHAI announced a MOU toicines did not meet all regulatory requirements

countries.

accelerate access to cefiderocol in low- and mid-because their respective clinical trials were con-dle-income countries.

ducted prior to the ICH guidelines. Shionogi does

No supply in access countries

not actively promote these medicines. However,C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

antibacterial and/or antifungal medicines. Its

in place for its educational programmesmarketing materials reflect emerging resist-

Shionogi performs strongly in conflict of interest

ance trends and/or include treatment guide-(COI) mitigation for the five AMR-related edu-

lines for healthcare professionals: for cefiderocol

Shionogi is active in multiple AMR surveil-

cational programmes for HCPs assessed by the(Fetroja®/Fetcroja®), doripenem (Finibax®) andlance programmes. It runs the multinational

Benchmark. To mitigate COI for one programme,

flomoxef (Flumarin®).

SIDERO-WT programme, which is focused on

it provides financial resources to an independ-

C.7

Active in multiple AMR surveillance programmes; openly publishes aggregatedresults

resistance against Gram-negative bacteria in
Makes one type of brochure and/or

13 countries and has been running since 2014.

gramme. The remaining four programmes havepackaging adaptation to facilitate appro-

Shionogi only shares the aggregated results

all three COI mitigation strategies looked for by

priate use by patients

through peer-reviewed open-access journal arti-

ent third party (Radio Nikkei) to develop the pro-

C.6

the Benchmark: (1) content is developed inde-

Shionogi adapts brochures to facilitate thecles, however, within 2021, it is planning to sharependently from its marketing department; (2) aappropriate use of cefcapene pivoxil (Flomox®)

the raw data on the AMR Register, an open-ac-

pledge not to provide financial or material incen-

by patients. Shionogi is middle-performing incess data platform. For the remaining pro-tives to participants; and (3) it does not use

this measure, taking account of paediatric use.

grammes, the aggregated results are sharedbranded materials.

It has created a brochure that is easy to under-

through peer-reviewed open-access journal arti-

stand using simple illustrations, which is tailoredcles, as well as on an open-access data platform

Fully decouples incentives for sales

to the treatment of children to improve paedi-

for the SENTRY programme (a programme man-agents from sales volumes, and engages

atric use.

aged by JMI laboratories).

C.5

in marketing practices to address appropriate use
Shionogi performs strongly in sales practices.
It reports that it fully decouples incentives forsales agents from sales volumes of its antibacterial and/or antifungal medicines.
Shionogi engages in marketing practices
that aim to address the appropriate use of its

137

Antimicrobial Resistance Benchmark 2021

ABT

Overall Performance
2020

2021

53% 69%▲

Access to Medicine Foundation

Abbott Laboratories
Generic medicine manufacturer
Stock exchange: NYSE • Ticker: ABT • HQ: Chicago, IL, US • Employees: 109,000

ABT
PERFORMANCE
Abbott performs well overall in its evaluated Research Areas compared

Performance in the Benchmark

0%

to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Performs well. Reports comprehensive
environmental risk-management strategy for own sites and suppliers;
quantifies discharge levels at all own sites.
Appropriate Access: Middle-performing. Files some of its off-patent/
generic medicines for registration in access countries. Reports somestrategies to expand access and ensure continuous supply of its relevant

incentives for sales agents from sales volumes for an anti-infective,

R&D

programmes. It adapts packaging for patients.

50%

100%

Points

0%

0/ 0

73%

Manufacturing

11/ 1553%

Access

8/ 15

80%

Stewardship
0%50%

12/ 15100%

How Abbott was evaluatedhowever it does not decouple such incentives for its other products.
It reports broad conflict of interest mitigation for its educational

/ 45
31/

Performance by Research Area

product.
Stewardship: Performs well. It ran a pilot where it fully decoupled

Points69%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR ABBOTTCHANGES SINCE 2020

Request and review discharge levels of all suppliers and increase public disclosure on environ-• In 2021, Abbott introduced a new contract

mental risk management. Abbott can expand its environmental risk management requirements totemplate for suppliers of APIs and drug prod-

all suppliers by fully implementing its supplier contract templete which outlines specific provisions

ucts with clauses that specifically requirefor AMR. Abbott currently requests and reviews discharge levels for only a subset of its suppliers.

implementation of AMR standards.

Abbott can also publicly disclose more information on how it manages environmental risk related to• In response to an opportunity from the 2020

antibacterial manufacturing. It can publish information on its progress in implementing the strategy,

AMR Benchmark, Abbott ran a new pilot in

the limits it sets, and the results of the audits of own and suppliers’ sites including antibacterial dis-which it fully decoupled incentives for sales

charge levels.

agents from sales volumes of an anti-infective

Expand registration and ensure availability of antibacterial and antifungal medicines. Abbott can
expand registration of its antibiotics and antifungals listed on the 2021 WHO EML, such as gen-in India for three months.
• Abbott is funder and member of the con-tamicin, itraconazole and tigecycline, to more countries, including low-income countries, with a highsortium VALUE-Dx. VALUE-Dx is the firstburden of disease. Further, it can expand equitable access in countries where medicines have been

Innovative Medicines Initiative project initiatedregistered.

by six in vitro diagnostic companies who work

Fully decouple incentives for sales agents from sales volumes. Abbott ran a pilot in India where itwith 20 non-industry partners to combat AMR

fully decoupled incentives for sales agents from sales volumes of an anti-infective for three months.
It can expand this practice to more countries where it markets antibacterial and/or antifungal medi-

and improve patient outcomes.
• Since 2020, Abbott has adapted packaging ofcines and to more relevant products.

eight of its antibacterial medicines, including

Comprehensively mitigate COI for educational programmes. Abbott organises medical educa-

amoxicillin and azithromycin, to take accounttion programmes for healthcare professionals on responsible use of antimicrobial medicines. It canof adherence to treatment, literacy and pae-

ensure that branded materials are not used in any educational programmes, as is now the case fordiatric use to facilitate the appropriate use ofsome.

such medicines by patients.

138

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

ABTNet sales by business segment

Therapeutic areas: Cardiovascular, Diabetes care, Gastro intestinal/immu-

2019 4,486

nity health, Infectious disease (Diagnostic, Covid-19), Metabolic disorders,

2020 4,303

7,647

10,8050

10,00020,000

Pain/central nervous system, Respiratory, Women’s health.
Business segments: Established pharmaceutical products, Nutritional
Product categories: Diagnostics, Generic medicines, Medical devices,
M&A since 2020: None in the antibacterial and/or antifungal sectors

7,713

12,23957

11,78766

30,000Established Pharmaceutical Products
Nutritional Products
Diagnostic Products

products, Diagnostic products, Medical devices
Vaccines

7,409

40,00050,000mn USD

40,00050,000mn USD

Medical Devices
Other

ABT
Net sales by region
11,3982019

11,534

13,0222020
012,58010,000

United StatesJapan
The Netherlands

20,00030,000GermanyIndia
All other countries

China
Switzerland

PORTFOLIO for pathogens in scope
Comparatively large portfolio: At least 85 products: 75 antibacterial medi-

ABT
Products on the market

cines; 3 antibacterial vaccines; 7 antifungal medicines
Off-patent/generic medicines: 10 of 85 were selected for analysis* (amoxicillin/clavulanic acid [A], amphotericin b [F], cefixime [W], clarithromycin

3
0

75 7
20

40

60

80

100

120

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine[W], clofazimine [T], colistin [R], gentamicin [A], itraconazole [F], linezolid[T], tigecycline [R])AWaRe medicines**: 16 Access group; 20 Watch group; 3 Reserve groupAnti-TB medicines**: 10

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Abbott is
not evaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
Comprehensive environmental risk-man-

Abbott expects external private waste-treat-agement for own sites and suppliers;

ment plants to comply with its general environ-tracks compliance with limits at own

mental standards. It audits these plants at least

sites

every five years (based on risk) which includes

and levels of antibacterial discharge from its
own or suppliers’ sites.
B.3

System in place to maintain production

Abbott reports a comprehensive strategy tochecking the suitability of technologies used

minimise the environmental impact of waste-

for processing waste and protocols for prevent-requests for official corrective action

waters and solid waste from antibacterial man-ing contamination. It also employs conservative

Abbott reports own sites and suppliers have aufacturing at its sites, including audits every

measures for effluents sent to external private

system to maintain high-quality antibacterial

three years. It reports setting discharge limits

and public wastewater treatment plants.

production consistent with international GMP

in the receiving environment for all antibacteri-quality for own and suppliers’ sites; nostandards. This includes periodic risk-based
Limited publicly available information on

audits and tracking of corrective and preven-limit AMR, as recommended the AMR Industry

environmental risk management

tive actions. Abbott also requires its suppliers to

Alliance. Discharge levels are quantified using

Abbott publishes some components of its envi-

audit their own suppliers. The Benchmark founda mass balance approach, verified by chemicalronmental risk-management strategy, with-no requests for official corrective action fromanalysis if applicable. It reports tracking compli-

out specific references to AMR. It does publish

the FDA or EMA related to non-conformities

ance with discharge limits of own sites.

having a programme in place to assess and min-with cGMP at Abbott’s own sites or any subsidi-

imise the impact of discharges, from own andaries that manufacture antibacterials.

als manufactured at its sites, based on PNECs to

Abbott requires third-party suppliers of anti-

B.2

bacterials to follow the same standards, includ-suppliers’ sites manufacturing APIs, on the envi-

ing limits based on PNECs. It reports conducting

ronment. Abbott does not publish: (1) the results

on-site audits every 3-5 years. It requests andof environmental audits, conducted at its own

reviews the discharge levels of its suppliers. A

sites, the sites of suppliers and/or external pri-

subset of its suppliers’ sites report to have quan-vate and public waste-treatment plants; (2) a list

tified discharge levels.

of these suppliers and plants; or (3) the limits* See Appendix VII for information about
eligibility criteria for products.
** Listed on the 2019 WHO EML.

139

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Abbott is not eligible for indicators: C1.1, C1.3,

Abbott reports two simplified treatment regi-

C.2.1 and C.2.3. For more information, seemens examples in Bolivia, India, and Peru. It esti-

Appendix VII.

mates its simplified treatment regimen containing clarithromycin to reach 5,000 cumulative

C.1.2 Filed to register 8 of 10 relevant off-pat-patients per year in Peru and Bolivia.

ent/generic medicines in 8 access countries on average

C.3

Several strategies to ensure continuous
supplyAbbott has an average performance, filing eightof its ten relevant off-patent/generic medi-

Abbott has an average performance, with strat-cines for registration in eight access countries

egies reported in all four areas assessed. It

on average. Its most widely filed relevant prod-ensures accurate demand planning and data

uct is the antibiotic clarithromycin filed in 58

sharing by having a monthly rolling forecast

access countries. Seven of its relevant productswith a 24-months horizon. Abbott mitigatesare filed in less than ten access countries. One ofagainst shortage risks by keeping a buffer stock

its relevant products is filed for registration in atfor critical APIs and finished products. It has

least one LIC.

a dual-sourcing strategy for its strategic APIs.
Abbott reports one technology transfer initiative

C.2.2 Limited information on strategies toof its drug product unit operations to a third-

expand access to off-patent/genericparty drug manufacturer. To mitigate against

medicines

substandard and falsified products, Abbott uses

Abbott has an average performance as it reports

packaging features, conducts employee’s train-

limited information on how it expands access toings, and tests potential falsified products in a

its ten relevant off-patent/generic medicines.

dedicated laboratory.

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Broad COI mitigation strategies in placevent the inappropriate use of its antibacterialon the packaging of eight antibacterial paediat-for its educational programmes

and/or antifungal medicines.

ric suspensions that directs to a video explaining

Abbott performs well in conflict of interest

Abbott engages in marketing practices that

how to use them appropriately.

(COI) mitigation for the five AMR-related edu-

aim to address the appropriate use of its anti-

cational programmes for HCPs assessed bybacterial and/or antifungal medicines. Its mar-C.7

the Benchmark. To mitigate COI for three pro-keting materials reflect emerging resistance

As a generic medicine manufacturer, Abbott isgrammes, it provides financial resources totrends and/or include treatment guidelines for

not assessed in this indicator but its activities inindependent third parties (APUA, Medscape,healthcare professionals: for clarithromycin.

AMR surveillance are reported. The Benchmark

BSAC and the University of Dundee) to develop

AMR Surveillancenotes that Abbott is active in two AMR surveilMakes three types of brochure and/lance programmes. It runs the national ARISE

COI mitigation strategies looked for by theor packaging adaptations to facilitate

programme, which is focused on regional sen-

Benchmark: (1) content is developed inde-appropriate use by patients

sitivity indices at a state level on hospital- andthe programme. One programme has all three

C.6

pendently from its marketing department;

Abbott adapts packaging to facilitate the appro-

community-acquired infections in India since(2) a pledge not to provide financial or mate-

priate use of its antibacterial medicines by

January 2019. Abbott only shares the data col-rial incentives to participants; and (3) it does

patients. Abbott performs strongly in this meas-

lected in this programme through a data plat-

not use branded materials. The remaining pro-ure, taking account of adherence to treatment,

form in a restricted manner. Moreover, thegramme has two of three COI mitigation strat-

literacy and paediatric use. It adapts the package

CANWARD programme is a national programmeegies looked for by the Benchmark: it is unclear

size of clarithromycin in eight countries to a fullmanaged by the Canadian Antimicrobial

whether branded materials are being used.

treatment course of either a 7-, 10-, or 14-day

Resistance Alliance with support from Abbott,treatment. Moreover, Abbott has dose marking

among others. Only the aggregated results

Engages in sales and marketing practices

on the packaging of cefixime in India to improve

are shared through an open-access data plat-to address appropriate use

patient adherence to treatment. Further, it

form, as well as through peer-reviewed journal

Abbott performs above average in sales prac-

includes a QR code on the packaging of amoxi-

articles.

tices. It ran a pilot in 2021 where it fully decou-

cillin that directs patients to information on thepled incentives for sales agents from sales vol-appropriate use and the course of treatment toumes of an anti-infective in India for three

improve adherence to treatment. Additionally,

months. However, outside of this pilot Abbott

Abbott adapts packaging for antibacterial medi-

does not report whether it decouples incentives

cines in India by including pictograms to support

for sales agents from sales volumes to help pre-literacy challenges. Finally, it includes a QR code

C.5*** 102 low- and middle-income countries where better access to medicine ismost needed.

140

Antimicrobial Resistance Benchmark 2021

ALK

Overall Performance
2020

2021

14% 20%▲Access to Medicine Foundation

Alkem Laboratories Ltd
Generic medicine manufacturer
Stock exchange: NSE • Ticker: ALKEM • HQ: Mumbai, India • Employees: 14,331

ALK
PERFORMANCE

Performance in the Benchmark

Alkem performs low overall in its evaluated Research Areas whenenvironmental risk-management strategy but without a specific aim to
limit AMR.
Appropriate Access: Performs low. Discloses no information onregistration filings, expanding access or ensuring continuous supply for
its off-patent/generic medicines.

packaging for patients.

50%

100%

Performance by Research Area
R&D

Points

0%

0/ 0

33%

Manufacturing

5/ 15

20%

Access

3/ 15

Stewardship

0/ 10
0%

Stewardship: Performs low. It does not report decoupling incentives
for sales agents from sales volumes. It does not adapt brochures or

/ 40
8/

0%

compared to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Performs low. Reports a general

Points20%

Overall score

50%

100%

How Alkem was evaluated

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR ALKEM

CHANGES SINCE 2020

Develop an AMR-specific environmental risk-management strategy and increase public disclo-

No changes are reported for Alkem.

sure. Alkem reports a commitment to manufacture its products in an environmentally responsible
manner without specifying whether AMR is taken into account. The company can develop an AMR
strategy for its own manufacturing sites, the sites of suppliers and external private waste-treatment
plants, based on the guidelines of the AMR Industry Alliance. This includes setting limits and quantifying discharge levels to track compliance. Moreover, Alkem can publish information on how it manages environmental risk related to antibacterial manufacturing to curb AMR. The company currently
publishes limited information.
Expand registration and ensure availability of antibacterial and antifungal medicines. Alkem can
expand registration and ensure equitable access of its antibiotics and antifungals listed on the 2021
WHO EML, such as cefotaxime and tigecycline, to more countries, including low-income countries,
with a high burden of disease. It can improve transparency on where its medicines are registeredand made available.
Apply responsible sales practices for antibacterial and antifungal medicines. Alkem can apply
responsible sales practices for antibacterial and antifungal medicines by not deploying sales agents.
Alternatively, it can fully decouple incentives for sales agents from sales volumes of such medicines.

* All companies were assessed based ondata submitted to the Benchmark in thecurrent and previous periods of analysis, as well as information the companies
have made publicly available, or that areaccessible through other sources. For
the 2021 Benchmark, Alkem declined
to submit data to the Antimicrobial
Resistance Benchmark.

141

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Access to Medicine Foundation

SALES AND OPERATIONS

ALK
Total income by business segment

Therapeutic areas: Anti-diabetes, Anti-infective, Cardiac, Dermatology,

2020*

Gastro-intestinal, Pain/analgesics, Neuro/CNS.

2021*

Business segments: Pharmaceuticals

83,443.6
88,650.1

0Product categories: Generic medicines

20,00040,00060,000100,000
mn INR*Financial year: April 2020 - March 2021

Pharmaceuticals

M&A since 2020: None in the antibacterial and/or antifungal sectors

80,000

ALK
Total income by region
56,062

2020*

58,2092021*
020,000India

United States

40,00021,99924,66560,00080,000100,000
mn INR
Other international markets*Financial year: April 2020 - March 2021

PORTFOLIO for pathogens in scopeMid-sized portfolio: At least 52 products: 49 antibacterial medicines; 3

ALK
Products on the market

antifungal medicines
Off-patent/generic medicines: 10 of 52 were selected for analysis**(amoxicillin [A], amoxicillin/clavulanic acid [A], caspofungin [F], cefixime

49 3
0

20

40

60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine[W], cefotaxime [W], colistin [R], isoniazid [T], itraconazole [F], linezolid[T], tigecycline [R])AWaRe medicines***: 5 Access group; 18 Watch group; 3 Reserve groupAnti-TB medicines***: 2

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Alkem is
not evaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
No AMR-specific environmental risk

audits, whether conducted at its own sites, theEMA related to non-conformities with cGMP atmanagement strategy

sites of suppliers or external private and public

Alkem’s own sites or any subsidiaries that manu-

Alkem states a general commitment to manufac-

waste-treatment plants; (2) a list of these sup-facture antibacterials.

ture its products in an environmentally responsi-

pliers and plants; or (3) the limits and levels of

ble manner, supported by a management systemantibacterial discharge from its own or suppli-that includes periodic impact assessments. It

ers’ sites.

is unclear how the strategy takes AMR into
account or aims to minimise the environmental impact of wastewaters and solid waste fromantibacterial manufacturing at its own sites,

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

third-party suppliers of antibacterials or external

Alkem reports that its own sites and suppliers

private and public waste-treatment plants.

have a system to maintain high-quality antibacterial production consistent with international

B.2

Limited publicly available information on

GMP standards. This includes periodic risk-based

environmental risk management

audits and tracking of corrective and preventive

Alkem publishes limited information on its

actions. There is limited information on whether

approach to environmental risk-management,

Alkem requires its suppliers to audit their own

without specific references to AMR. It does

suppliers. The Benchmark found no requests

not publish: (1) the results of environmental

for official corrective action from the FDA or** See Appendix VII for information about
eligibility criteria for products.
*** Listed on the 2019 WHO EML.

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C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries†
Alkem is not eligible for indicators: C.1.1, C.1.3,

C.3

Appendix VII.

No information on strategies to ensure
continuous supply

C.2.1 and C.2.3 For more information, see

Alkem’s performance is low as it discloses noinformation on how it ensures the continuous

C.1.2 No information on registration filings foroff-patent/generic medicines

supply of its relevant products to access countries, beyond India.

Alkem’s performance is low. It reports no evidence of filing its ten relevant off-patent/generic
medicines for registration in access countries,
beyond India.
C.2.2 No information on strategies to expand
access to off-patent/generic medicines
Alkem’s performance is low as it discloses noinformation on how it expands access to its ten
relevant off-patent/generic medicines, beyond
India. It does not provide evidence of patientreach and geographic reach.

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Educational Stewardship Activities

icines as its marketing materials do not reflect

There is no information regarding Alkem’s

emerging resistance trends or include treatment

involvement in AMR-related educational pro-

guidelines for healthcare professionals to raisegrammes aimed at healthcare professionals andawareness of AMR and address appropriate use.

it is therefore not eligible for this indicator as
there is no conflict of interest mitigation to be

C.6

Does not report adapting brochures and/or packaging to facilitate appropriate

assessed.

use by patients
C.5

Does not report sales or marketing prac-

Alkem does not report adapting brochures and/tices that aim to address appropriate useor packaging to facilitate the appropriate use of

Alkem performs low in sales practices. It does

its antibacterial and/or antifungal medicines by

not report whether it decouples incentives forpatients.

sales agents from sales volumes to help preventthe inappropriate use of its antibacterial and/or

C.7

antifungal medicines.

As a generic medicine manufacturer, Alkem is

AMR Surveillance

Alkem does not report to engage in market-

not assessed in this indicator nor does it reporting practices that aim to address the appropriate

any involvement in AMR surveillance activities.

use of its antibacterial and/or antifungal med-† 102 low- and middle-income countries
where better access to medicine is mostneeded.

143

Antimicrobial Resistance Benchmark 2021

AUR

Overall Performance
2020

2021

31% 71% ▲Access to Medicine Foundation

Aurobindo Pharma Ltd
Generic medicine manufacturer
Stock exchange: NSE • Ticker: AUROPHARMA • HQ: Hyderabad, India • Employees: 23,000

AUR
PERFORMANCE
Aurobindo is the leader among the generic medicines manufacturers in

Performance in the Benchmark

0%

scope and performs well in its evaluated Research Areas.
Responsible Manufacturing: Performs well. Reports environmental riskmanagement strategy for own sites and suppliers; co-leads in reporting
compliance with limits at own sites.
Appropriate Access: Middle-performing. Files its off-patent/generic
medicines for registration in access countries. Reports some strategies
to expand access and ensure continuous supply of its relevant product.

comprehensive conflict of interest mitigation for its educational

/ 45
32/

50%

100%

Performance by Research Area
R&D

Points

0%

0/ 0

67%

Manufacturing

10/ 1560%

Access

9/ 15

87%

Stewardship0%

Stewardship: Performs strongly. It does not promote antibacterial
and/or antifungal medicines to healthcare professionals. It reports

Points71%

Overall score50%

13/ 15100%

How Aurobindo was evaluatedprogramme. It adapts brochures for patients.
A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR AUROBINDOCHANGES SINCE 2020

Increase public disclosure on environmental risk management. Aurobindo publishes information• Since 2020, Aurobindo has extended the envi-

on some of the components of its general environmental risk-management strategy. It can publish

ronmental risk management strategy require-more information on how it manages environmental risk related to antibiotic discharge in to envi-

ments of its own sites to its suppliers.

ronment to curb AMR. While Aurobindo reports that all its own sites are compliant with set limits,• Since 2020, Aurobindo reports that all its own

it can provide clear evidence by publicly disclosing its progress in implementing the strategy andsites that manufacture antibacterials are com-

by publishing the audit results of own and suppliers’ sites, including antibacterial discharge levels if
applicable.

pliant with discharge limits.
• Aurobindo reports that it fully decouples

Expand access and ensure adequate supply of antibacterial and antifungal medicines in more

incentives for sales agents from sales volumes

access countries. Aurobindo has a Day-1 generic policy by which it introduces a generic product asin emerging markets to help prevent the inap-

soon as the patent on a brand expires for the EU and USA. It can expand access to its generic anti-

propriate use of its antibacterial medicine. It

biotics and antifungals listed on the 2021 WHO EML to more products and countries, allowing forsells antibacterial and antifungal medicines

generic options to be made available in access countries as soon as the originator’s patent expires.

only through tenders in Europe and the US.

Expand adaptations to brochures and packaging to consider more patient needs. In order to support the appropriate use of its antibacterial and/or antifungal medicines by patients, Aurobindo
adapts brochures to take account of local languages. It can further adapt its brochures and packaging to consider literacy levels, paediatric use, environmental conditions and patient adherence totreatment.

144

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SALES AND OPERATIONS

AUR
Total income by business segment

Therapeutic areas: Anti-allergies, Antibiotics, Anti-diabetics, Anti-retroviral,

2020*

Cardio-vascular (CVS), Central nervous system (CNS), gastroenterology.

2021*

Business segments: Pharmaceuticals (including APIs and formulations)0

Product categories: Generic medicines, Biosimilars

230,985.1
247,746.2
100,000

200,000

300,000
mn INR*Financial year: April 2020 - March 2021

Pharmaceuticals

M&A since 2020: In February 2020, Aurobindo finalised acquisition of certain Profectus BioSciences Inc assets, including preventative and therapeutic R&D assets to develop vaccine for infectious diseases, for USD 11.29 mn
and created a new subsidiary called Auro Vaccines LLC.

AUR
Total income by region
2020*

116,782.6

2021*

121,174.9

050,000India

United States

100,000

72,767.6
81,221.6

150,000

Europe200,000

250,000
300,000
mn INR
Rest of world*Financial year: April 2020 - March 2021

PORTFOLIO for pathogens in scopeMid-sized portfolio: At least 39 products: 32 antibacterial medicines; 2antibacterial vaccines; 5 antifungal medicines
Off-patent/generic medicines: 6 of 39 were selected for analysis* (amoxicillin [A], amoxicillin/clavulanic acid [A], cefuroxime [W], ciprofloxacin [W],fluconazole [F], terbinafine [F])

AUR
Products on the market
2
0

32 5
20

40

60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

AWaRe medicines**: 11 Access group; 18 Watch group; 2 Reserve groupAnti-TB medicines**: 1

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Aurobindo
is not evaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
Environmental risk-management for own

regulatory standards. It reports auditing the pri-sites and suppliers; tracks compliancevate plants on a yearly basis which includes

with limits at own sites

B.3

System in place to maintain production
quality for own and suppliers’ sites; regu-

checking the suitability of technologies used forlator requested official corrective action

Aurobindo reports a strategy to minimise theprocessing waste and protocols for preventing

Aurobindo reports that its own sites and suppli-

environmental impact of wastewaters and solid

contamination.

ers have a system to maintain high-quality anti-

waste from antibacterial manufacturing at its

bacterial production consistent with internaPublicly discloses some information ontional GMP standards. This includes periodic

reports setting discharge limits for all antibacte-environmental risk managementrisk-based audits and tracking of corrective andrials manufactured at its sites, based on PNECs

Aurobindo publishes some components of its

preventive actions. There is limited informa-

to limit AMR, as recommended by the AMR

environmental risk-management strategy. Thistion on whether Aurobindo requires its suppli-

Industry Alliance. It also reports quantifying dis-

includes disclosure of the ongoing implemen-

ers to audit their own suppliers. In September

charge levels at all sites using a mass balancetation of necessary processes to deactivate

2019, an FDA drug quality inspection identified

approach, supported by chemical analysis for

API residues in wastewater. Since 2019, it is a

non-conformities with cGMP at one of the com-beta-lactams and cephalosporins. All its 15 sites,

member of the AMR Industry Alliance, which

pany’s sites that manufactures antibacterialsof which 4 are ZLD, are reported to be compliant

publishes a list of recommended antibacte-(Polepally, Mahaboob Nagar, India), resulting inwith discharge limits.

rial discharge targets. Aurobindo publishes that

official requests for corrective action. Aurobindo

Aurobindo requires third-party suppliers

mass balance estimations of antibiotics are con-reports that the issue of non-conformities withof antibacterials to follow the same standards,

ducted. The corresponding results or the dis-cGMP have since been resolved with no impact

including audits every five years. It reports pro-charge levels themselves are not published.

on business continuity, but the regulatory status

curing around 1% of its antibacterial API volume

Aurobindo also does not publish: (1) the results

remains as is because of delays to FDA inspec-from 2 supplier sites, which are both ZLD sites.

of environmental audits, whether conducted attions due to the COVID-19 pandemic.

No antibacterial drug products are procured

its own sites, the sites of suppliers or externalfrom suppliers.

private and public waste-treatment plants; (2) asites, including audits at least every five years. It

Aurobindo requires external private andB.2

list of these suppliers and plants.

public waste-treatment plants to follow local* See Appendix VII for information about
eligibility criteria for products.
** Listed on the 2019 WHO EML.

145

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C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Aurobindo is not eligible for indicators: C.1.1,

tributors. Between April 2020 and March 2021,

icines. To mitigate against substandard and fal-

C.1.3, C.2.1 and C.2.3. For more information, see

Aurobindo estimates to have reached 600,000

sified products, it uses security features suchAppendix VII.

patients in Vietnam with its amoxicillin/clavu-

as tamper-proof stickers, hot-glue sealing tech-lanic acid generic version.

niques, self-destructing packing materials andC.1.2 Filed to register off-patent/generic medicines in 19 access countries on average

serialisation.
C.3

Some strategies to ensure continuous
supplyAurobindo performs above average, filing all its
six relevant off-patent/generic medicines for

Aurobindo has an average performance, withregistration in 19 access countries on average.

strategies reported in all four areas assessed.

Its most widely filed relevant product is amoxi-

It ensures accurate demand planning and data

cillin/clavulanic acid filed in 35 access countries.

sharing by having a monthly rolling forecast.

Two of its relevant products are filed in less than

Aurobindo has a direct-selling model where

10 access countries. Five of its relevant products

demand is directly generated by its customers or

are filed for registration in at least one LIC.

driven by tenders. Aurobindo mitigates against
shortage risks by keeping a buffer stock for its

C.2.2 Some strategies to expand access to

key starting material, APIs and finished prod-

off-patent/generic medicines

ucts. It reports manufacturing more than 99%

Aurobindo has an average performance. It aimsof its API in-house. Aurobindo’s manufacturing

to expand access to its off-patent/generic med-facilities are located in India. It supplies APIs to

icines in access countries through afforda-

low- and middle-income countries and aims toble prices, tenders and direct sales to its dis-

improve their capacity to produce finished med-C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

mote such medicines to healthcare profession-in place for its educational programmeals, the company is not eligible to be assessed on

Aurobindo performs strongly in conflict of inter-marketing materials.

est (COI) mitigation for the one AMR-related
educational programme for HCPs assessed

C.6

Makes one type of brochure and/or
packaging adaptation to facilitate appro-by the Benchmark. The programme has all

priate use by patients

three COI mitigation strategies looked for by
the Benchmark: (1) content is developed inde-

Aurobindo adapts brochures to facilitate thependently from its marketing department; (2) aappropriate use of amoxicillin/clavulanic acid bypledge not to provide financial or material incen-

patients. It is middle-performing in this meas-

tives to participants; and (3) a policy of not using

ure, taking account of language. Aurobindo hasbranded materials.

translated package inserts for amoxicillin/clavulanic acid in Vietnamese.

C.5

Does not promote its antibacterial and/or antifungal medicines

C.7

AMR Surveillance

Aurobindo performs strongly in sales practices.

As a generic medicine manufacturer, Aurobindo

It does not deploy any sales agents to promote

is not assessed in this indicator nor does it report

its antibacterial and/or antifungal medicines toany involvement in AMR surveillance activities.

healthcare professionals. Since Aurobindo does
not develop or use marketing materials for antibacterial and/or antifungal medicines to pro-*** 102 low- and middle-income countries where better access to medicine ismost needed.

146

Antimicrobial Resistance Benchmark 2021

CPL

Overall Performance
2020

2021

70% 60%▼Access to Medicine Foundation

Cipla Ltd
Generic medicine manufacturer
Stock exchange: NSE • Ticker: CIPLA • HQ: Mumbai, India • Employees: 25,672

CPL updated 2nov
PERFORMANCE
Cipla performs above average overall in its evaluated Research Areas

Performance in the Benchmark

0%when compared to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Performs well. Reports environmental riskmanagement strategy for own sites; initial risk assessment of suppliers
ongoing.
Appropriate Access: Middle-performing. Filed its on-patent medicine in
India. Files some of its off-patent/generic medicines for registration inaccess countries. Reports some strategies to ensure continuous supply

from sales volumes for >99%. It reports comprehensive conflict of

R&D

50%

100%

Points

0%

0/ 0

67%

Manufacturing

10/ 1540%

Access

10/ 2587%

Stewardship
0%50%

13/ 15100%

How Cipla was evaluatedinterest mitigation for its educational programmes. It adapts brochures
and packaging for patients.

/ 55
33/

Performance by Research Areaof its relevant product.
Stewardship: Performs strongly. It decouples incentives for sales agents

Points60%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR CIPLACHANGES SINCE 2020

Expand environmental risk-management strategy to include suppliers and ensure compliance• As part of the 3-year strategy (2020-2023),

with limits. Cipla tracks compliance with discharge limits it set for its own manufacturing sites.

Cipla will submit and launch plazomicin in India

It can quantify discharge levels at all suppliers’ sites and track compliance with limits, and pub-and other countries, as well as explore multi-

licly disclose the results. It can also publicly disclose the names and locations of its suppliers andwaste-treatment plants for increased transparency.

ple opportunities to out-license the product.
• Since 2020, Cipla is in the process of assess-

Expand registration antibacterial medicines to more access countries and ensure adequate

ing all its suppliers related to the risk of AMR,

supply. Cipla can expand registration of its antibiotics and antifungals listed on the 2021 WHO EML,

including requesting data from suppliers onsuch as itraconazole and levofloxacin to more countries, including low-income countries and ensure
adequate supply. To ensure adequate supply, Cipla can promote capacity building and technology
transfer initiatives in access countries, to improve access to its medicines.

discharge levels.
• Since 2020, Cipla is no longer a member ofthe AMR Industry Alliance.

Fully decouple incentives for sales agents from sales volumes. Cipla links part of its sales agents’• In June 2020, Cipla withdrew its EMA appli-

incentives to sales volumes. It can fully decouple incentives for sales agents from sales volumes ofcation for a marketing authorisation of pla-

antibacterial and antifungal medicines again.

zomicin (Zemdri®), to treat complicated urinary tract infection, due to lack of financial
viability.

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Access to Medicine Foundation

SALES AND OPERATIONSCPLRevenue by business segment

Therapeutic areas: Cardiovascular diseases, Central nervous system,

2020*

Dermatology, Diagnostics, Gastrointestinal, Infectious diseases, Metabolic

2021*

disorders, Oncology, Ophthalmology, Orthopaedics, Respiratory diseases,

0

Urology, Women’s Health.

169,586.7
188,782.4
50,000

Pharmaceuticals

Business segments: Pharmaceuticals, New ventures
Product categories: Biosimilars, Consumer health products, Generic medi-

100,000

200,000
mn INR*Financial year: April 2020 - March 2021

New Ventures

150,000

CPL
Revenue by regioncines, Innovative medicines, Respiratory devices.

67,405.6

2020*

M&A since 2020: None in the antibacterial and/or antifungal sectors

0
India

38,738.2

77,357.32021*

50,000
United States

43,111.9

40,914 23,030
100,000

50,294.6

200,000
mn INR
Rest of world*Financial year: April 2020 - March 2021

South Africa

150,000

PORTFOLIO for pathogens in scopeMid-sized portfolio: At least 59 products: 46 antibacterial medicines; 13
antifungal medicines

CPL
Products on the market
0On-patent medicine: 1 (plazomicin)
Off-patent/generic medicines: 9 of 58 were selected for analysis* (amox-

0

46
20

40

13
60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

icillin [A], amoxicillin/clavulanic acid [A], ciprofloxacin [W], colistin [R], fluconazole [F], Fosfomycin [R], itraconazole [F], levofloxacin [W], linezolid[T])
AWaRe medicines**: 5 Access group; 15 Watch group; 8 Reserve groupAnti-TB medicines**: 3

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Cipla is notevaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
Environmental risk-management includ-

34 of 57 supplier sites, or 60%, are fully assessed

own sites, the sites of suppliers or external pri-

ing limits for own sites; tracks compli-

but it is unclear how many of the 34 have quanti-

vate and public waste-treatment plants; (2) a list

ance with limits at own sites

fied discharge levels. Complete assessment of allof these suppliers and plants; or (3) the limits

suppliers is expected by March 2022.

and levels of antibacterial discharge from its

Cipla reports a strategy to minimise the environmental impact of wastewaters and solid

There is limited information on the require-

waste from antibacterial manufacturing at its

ments Cipla makes of external private and publicsites, including audits. It reports setting dis-waste-treatment plants, in terms of environmen-

charge limits in the receiving environment for all

tal strategy and antibacterial discharge limits.

antibacterials manufactured at its sites, based

Cipla reports that it requests flow rates fromon PNECs to limit AMR, as recommended bycommon effluent treatment plants to accurately

Cipla reports that its own sites and suppliers

the AMR Industry Alliance. Discharge levels are

determine dilution factors and mass balance

have a system to maintain high-quality antibac-

quantified using a mass balance approach, veri-

calculations.

terial production consistent with international

fied by chemical analysis if applicable. It reports

own or suppliers’ sites.
B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

GMP standards. This includes periodic riskPublicly discloses some information on

based audits and tracking of corrective and pre-and two, or 20%, of those are compliant withenvironmental risk management andventive actions. Cipla also requires its suppli-

discharge limits. It also reports that the levels of

AMR risk identification of own sites

ers to audit their own suppliers. The Benchmark

70% of all antibacterials are quantified and 100%

Cipla publishes some components of its environ-found no requests for official corrective action

is expected by March 2022.

mental risk-management strategy. It publishes

from the FDA or EMA related to non-conform-

Cipla will require third-party suppliers ofthat the risk of AMR at all own sites is assessed

ities with cGMP at Cipla’s own sites or any sub-antibacterials to follow similar standards, includ-and priority sites are implementing responsible

sidiaries that manufacture antibacterials.

ing limits based on PNECs, after it completes thepractices related to AMR. It also publishes thatongoing initial assessments of all its 57 suppliers.

risk assessments of its supplier sites are ongo-

It requests and reviews discharge levels of its

ing. Cipla does not publish: (1) the results ofsuppliers as part of the assessments. It reports

environmental audits, whether conducted at its

three of 10 sites have quantified discharge levels* See Appendix VII for information about
eligibility criteria for products.
** Listed on the 2019 WHO EML.

B.2

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C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Cipla is not eligible for indicators: C.1.3 and C.2.3.

LIC.

Q-TIB, a fixed dose combination used in tuber-

For more information, see Appendix VII.

culosis prevention for people living with HIV, in
C.2.1 Expanding access to on-patent

C.1.1

Registration filings for relevant on-patent medicines

medicines

seven access countries including Haiti, Rwanda
and Uganda.

Cipla ’s performance is low as its on-patent med-

Cipla’s performance is low as it filed its newly

icine, plazomicin, (Zemdri®) is not yet marketed

acquired on-patent medicine, the reserve anti-in access countries.

biotic plazomicin (Zemdri®) used to treat com-

C.3

Some strategies to ensure continuous
supplyCipla has an average performance with strateC.2.2 Some strategies to expand access togies reported in three of four areas assessed.

off-patent/generic medicines

It ensures accurate demand planning and data

Cipla has an average performance. It reports

sharing by having a 12-month rolling forecast

several examples to demonstrate the number

and conducting long-term demand planning (upof people who benefitted from its eligible med-

to five years). Cipla mitigates against shortage

Cipla has an average performance, filing eight oficines in India and South Africa during therisks by keeping safety stocks and securing suf-

its nine relevant off-patent/generic medicines

COVID-pandemic peak. For example, Cipla’s

ficient APIs stocks. Cipla does not report capac-

for registration in six access countries on aver-colistin is available in 500 Indian hospitals andity building and technology transfer initiatives.

age. Its most widely filed relevant product is thewas used to treat 20,000 Indian patients per

To mitigate against substandard and falsified

antifungal fluconazole, filed in 21 access coun-month. In South Africa, Cipla estimates to haveproducts, Cipla uses an automated Track&Tracetries. Six of its relevant products are filed in lessprovided access to azithromycin to 280,000

system and product or primary packaging

than 10 access countries. Three of its relevant

patients. In 2020 and 2021, Cipla participated inserialisation.

products are filed for registration in at least one

a tender to distribute more than 1 mn tablets ofplicated urinary tract infections, in one accesscountry (India).
C.1.2 Filed to register off-patent/generic medicines in 4 access countries on average

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

aim to address the appropriate use of its anti-

C.7

in place for its educational programmes

bacterial and/or antifungal medicines. Its mar-

As a generic medicine manufacturer, Cipla is not

Cipla performs strongly in the analysis of its

keting materials reflect emerging resistanceassessed in this indicator but its activities in AMR

top five AMR-related educational programmes

trends and/or include treatment guidelines

surveillance are reported. The Benchmark notes

for healthcare professionals in conflict of inter-for healthcare professionals: for colistin andthat Cipla funds a surveillance programme in theest (COI) mitigation. All five programmes haveitraconazole.

US focused on resistance to plazomicin and has

all three COI mitigation strategies looked for by

AMR Surveillance

been running since 2018. The programme is an
Makes two types of brochure and/FDA postmarketing requirement and data col-pendently from its marketing department; (2)or packaging adaptations to facilitatelection is not complete, therefore data is notparticipants are not provided financial or mate-appropriate use by patients

yet shared publicly. However, Cipla reports thatthe Benchmark: (1) content is developed inde-

C.6

rial incentives; and (3) a policy of not using

Cipla adapts brochures and packaging to facili-

aggregated results are shared and presented atbranded materials.

tate the appropriate use of itraconazole, amo-international infectious disease conferences.

rolfine, oxiconazole and fosfomycin trometamol
C.5

Engages in sales and marketing practices

by patients. Cipla performs well in this meas-

to address appropriate useure, taking account of language and adherence

Cipla performs above average in sales practices.

to treatment. It provides packages and leaflets

It reports that it partly decouples incentives forfor these products with QR codes that direct

sales agents from sales volumes of its antibacte-patients to information on antifungal resist-rial and/or antifungal medicines. Its percentage

ance in eight to ten regional languages in India.

of variable pay linked to sales volumes is <1% andThis information aims to improve adherence tosales targets are set at the national level.

treatment.

Cipla engages in marketing practices that*** 102 low- and middle-income countries where better access to medicine ismost needed.

149

Antimicrobial Resistance Benchmark 2021

FRK

Overall Performance
2020

2021

55% 63%▲

Access to Medicine Foundation

Fresenius Kabi AG
Generic medicine manufacturer
Stock exchange: XFRA • Ticker: FRE (Fresenius SE & Co KGaA)* • HQ: Bad Homburg, Germany • Employees: 40,519

FRK
PERFORMANCE
Fresenius Kabi performs above average overall in its evaluated Research

Performance in the Benchmark

0%

Areas when compared to the other generic medicine manufacturers inscope.
Responsible Manufacturing: Middle-performing. Reports environmental
risk-management strategy for own sites; limited information on whether
AMR and discharge limits are taken into account.
Appropriate Access: Middle-performing. Files some of its off-patent/
generic medicines for registration in access countries. Reports some

Stewardship: Performs well. It decouples incentives for sales agents

R&D

50%

100%

Points

0%

0/ 0

60%

Manufacturing

9/ 15

53%

Access

8/ 15

80%

Stewardship
0%

50%

8/ 10
100%

How Fresenius Kabi was evaluatedfrom sales volumes by using tender sales for most sales. It reports broad
conflict of interest mitigation for its educational programmes.

/ 40
25/

Performance by Research Area

strategies to expand access and ensure continuous supply of its relevant
products.

Points63%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR FRESENIUS KABICHANGES SINCE 2020

Integrate AMR in environmental risk-management strategy and increase public disclosure.

• Fresenius Kabi increased the number of regis-

Fresenius Kabi reports an environmental risk management strategy that includes auditing processes

tration filings in access countries for eight out

and recently became a member of the AMR Industry Alliance. The company can integrate AMR inof 10 of its relevant off-patent/generic anti-

its strategy for its own manufacturing sites, the sites of suppliers and external private waste-treat-bacterial and antifungal medicines, compared

ment plants, based on the guidelines of the AMR Industry Alliance. This includes setting limits andto four out of 10 in 2020, meeting the oppor-

quantifying discharge levels to track compliance. Moreover, Fresenius Kabi can publish informa-tunity provided in the 2020 Benchmark. Theytion on how it manages environmental risk related to antibacterial manufacturing to curb AMR. The

also increased registration to seven accesscompany currently publishes limited information.

countries on average from four on average

Expand availability and ensure continuous supply of antibacterial and antifungal medicines tosince 2020.

more access countries. Fresenius Kabi expands access through direct selling contracts or tenders• In 2020, Fresenius Kabi became a member ofand reports a set of cost-containment measures. It also reports to ensure accurate demand plan-

the AMR Industry Alliance stating a commit-

ning and data sharing. Fresenius Kabi can ensure equitable access and adequate supply of its antibi-ment to apply its corresponding guidelines forotics and antifungals listed on the 2021 WHO EML in more access countries. For example, Fresenius

manufacturing going forward.

Kabi can build on capacity or mitigate against shortages by working with several API suppliers.
Expand registration of antibacterial and antifungal medicines. Fresenius Kabi reports developing
generic IV formulations that are ready to launch directly after the patents of the branded products
expire. It can apply this policy in access countries and register its antibiotics and antifungals listedon the 2021 WHO EML, (e.g. daptomycin and caspofungin), in more countries, including in low-income countries with a high burden of disease.

* Fresenius Kabi AG is a business segmentof Fresenius SE & Co. KGaA

150

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONSFRKSales by business segment

Therapeutic areas: Anaesthesia, Critical illness, Fluid management,

2019

Liver insufficiency, Maldigestion / malabsorption, Oncology, Paediatrics,

2020

Transfusion medicine.

6,919
6,976
0

Business segments: Fresenius Kabi

2,000

4,000

6,000

8,000

10,000mn EUR

8,000

10,000mn EUR

Fresenius Kabi

Product categories: Biosimilars, Generic medicines, Medical devices
M&A since 2020: None in the antibacterial and/or antifungal sectors

PORTFOLIO for pathogens in scope

FRK
Sales by region (Fresenius Kabi)
2019

2,313

2,424

2020

2,458

2,376

0

2,000

EuropeNorth America

2,182
2,142

4,000

6,000

Emerging markets

FRK
Products on the market

Mid-sized portfolio: At least 51 products: 48 antibacterial medicines; 3 antifungal medicines
Off-patent/generic medicines: 10 of 51 were selected for analysis** (azt-

0
0

48 3
20

40

60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

reonam [R], caspofungin [F], clindamycin [A], daptomycin [R], fluconazole[F], isoniazid [T], linezolid [T], meropenem [W], metronidazole [A], piperacillin/tazobactam [W])AWaRe medicines***: 16 Access group; 22 Watch group; 5 Reserve groupAnti-TB medicines***: 3

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Fresenius
Kabi is not evaluated in this Research Area.

B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Environmental risk-management for own

nal private and public waste-treatment plants, inpliers and plants; or (3) the levels of antibacterialsites; questionnaire-based assessments

terms of environmental strategy, audits and anti-

discharge from its own or suppliers’ sites.

of all suppliers

bacterial discharge limits and levels. It reports

Fresenius Kabi reports a strategy to minimise

external waste disposal companies are regularly

the environmental impact of wastewaters andaudited but exact audit parameters are definedsolid waste from antibacterial manufacturinglocally by each site.

at its sites, including audits every 1-4 years. It

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

Fresenius Kabi reports own sites and suppliers
Publicly discloses some information on

have a system to maintain high-quality antibac-

in 2020 and plans to set discharge limits andenvironmental risk management

terial production consistent with international

quantify levels at its sites in the near future.

Fresenius Kabi publishes some components

GMP standards. This includes periodic risk-basedof its environmental risk-management strat-

audits and tracking of corrective and preven-ments that Fresenius Kabi makes of third-party

egy, without specific references to AMR. It does

tive actions. It also reviews, as part of its exter-

suppliers of antibacterials with respect to AMR.

publicly disclose that non-recyclable hazardous

nal audit process, the results of audits that sup-It reports conducting a questionnaire-based CSR

waste including antibiotics is mainly incinerated.

pliers conducted with their own suppliers. The

assessment of all suppliers which includes ques-

Since 2020, it is a member of the AMR Industry

Benchmark found no requests for official cor-

tions on how antibacterial waste is processed

Alliance, which publishes a list of recommended

rective action from the FDA or EMA related toby suppliers. It does not report requiring suppli-

antibacterial discharge targets. Fresenius Kabi

non-conformities with cGMP at Fresenius Kabi’s

ers to set discharge limits or quantify discharge

does not publish: (1) the results of environmental

own sites or any subsidiaries that manufacturelevels.

audits, whether conducted at its own sites, theantibacterials.

became a member of the AMR Industry Alliance

There is limited information on the require-

B.2

There is also limited information on thesites of suppliers or external private and public

requirements Fresenius Kabi makes of exter-

waste-treatment plants; (2) a list of these sup-** See Appendix VII for information about
eligibility criteria for products.
*** Listed on the 2019 WHO EML.

151

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries†
Fresenius Kabi is not eligible for indicators: C.1.1,

C.2.2 Some strategies to expand access to

Details were provided under the basis of confi-

C.1.3, C.2.1 and C.2.3. For more information, see

off-patent/generic medicines

dentiality. It conducts internal or external audits

Fresenius Kabi has an average performance. Itof its suppliers, ensures compliance to the ISO

expands access to its off-patent/generic med-and GMP standards, evaluates its supply perfor-

icines in access countries through direct sales

mance through KPIs and has a Supplier Codecontracts or tenders. Fresenius Kabi reports aof Conduct. Fresenius Kabi reports, subject toFresenius Kabi has an average performance,

set of cost-containment measures applied on

confidentiality, where it produces antibiotics

filing eight of its 10 relevant off-patent/genericits generic medicines, leading to lower prices. It

in low- and middle-income countries. To mit-

medicines for registration in seven access coun-provides some evidence of patient reach. Details

igate against substandard and falsified prod-

tries on average. Its most widely filed relevant

were provided under the basis of confidentiality.

ucts, Fresenius Kabi has implemented a Global

Appendix VII.
C.1.2 Filed to register off-patent/generic medicines in 7 access countries on average

product is the antifungal metronidazole filed in
21 access countries. Seven of its relevant prod-

Serialisation Program.
C.3

Some strategies to ensure continuous
supplyucts are filed in less than ten access countries.
Two of its relevant products are filed for regis-

Fresenius Kabi has an average performance, withtration in at least one LIC.

strategies reported in all four areas assessed.
It ensures accurate demand planning and data
sharing and mitigates against shortages risks.

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Broad COI mitigation strategies in placetices that aim to address the appropriate use offor its educational programmes

its antibacterial and/or antifungal medicines. Its

Fresenius Kabi performs well in conflict of inter-marketing materials include emerging resistanceest (COI) mitigation for the five AMR-related

trends and/or include treatment guidelines foreducational programmes for HCPs assessed

healthcare professionals: for a range of its intra-by the Benchmark. Four programmes have all

venous antibacterial medicines used in intensive

three COI mitigation strategies looked for bycare units.

the Benchmark: (1) content is developed independently from its marketing department; (2) aC.6

pledge not to provide financial or material incen-

Stewardship-Oriented Adaptations forPatients

tives to participants; and (3) a policy of not using

Fresenius Kabi is not eligible for this indicator

branded materials. The remaining programme

as its medicines are administered by healthcare

has two COI mitigation strategies: the con-professionals in the hospital setting so there istent is developed by Fresenius Kabi’s marketing

no need to adapt brochures and/or packaging todepartment.

facilitate the appropriate use of its antibacterial
and/or antifungal medicines by patients.

C.5

Engages in sales and marketing practices
to address appropriate use

C.7

AMR SurveillanceFresenius Kabi performs above average in sales

As a generic medicine manufacturer, Fresenius

practices. It reports that it sells most of its anti-

Kabi is not assessed in this indicator nor does

bacterial and/or antifungal medicines throughit report any involvement in AMR surveillance

hospital tenders and does not have sales incen-

activities.

tives linked to the sales volume of these tenders.
Fresenius Kabi engages in marketing prac-† 102 low- and middle-income countries
where better access to medicine is mostneeded.

152

Antimicrobial Resistance Benchmark 2021

HNH

Overall Performance
2020

6%

2021

15% ▲

Access to Medicine Foundation

Hainan Hailing Chemipharma Corp Ltd
Generic medicine manufacturer
Stock exchange: Privately held • Ticker: N/A • HQ: Haikou, China • Employees: 600

HNH
PERFORMANCE

Performance in the Benchmark

Hainan Hailing performs low overall in its evaluated Research Areas

environmental risk-management strategy but without a specific aim to
limit AMR.
Appropriate Access: Performs low. Discloses no information onregistration filings, expanding access or ensuring continuous supply for
its off-patent/generic medicines.

packaging for patients.

50%

100%

Performance by Research Area
R&D

Points0%

0/ 0Manufacturing

20%

3/ 15

Access20%

3/ 15

Stewardship

0/ 10
0%

Stewardship: Performs low. It does not report decoupling incentives
for sales agents from sales volumes. It does not adapt brochures or

/ 40
6/

0%

when compared to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Performs low. Reports a general

Points15%

Overall score

50%

100%

How Hainan Hailing was evaluated

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR HAINAN HAILINGCHANGES SINCE 2020

Develop an AMR-specific environmental risk-management strategy and increase public dis-

No changes are reported for Hainan Hailing.

closure. Hainan Hailing reports a commitment to manufacture its products in an environmentally responsible manner without specifying whether AMR is taken into account. The company candevelop an AMR strategy for its own manufacturing sites, the sites of suppliers and external private
waste-treatment plants, based on the guidelines of the AMR Industry Alliance. This includes setting
limits and quantifying discharge levels to track compliance. Moreover, Hainan Hailing can publish
information on how it manages environmental risk related to antibacterial manufacturing to curb
AMR. The company currently publishes limited information.
Expand registration and ensure availability of antibacterial and antifungal medicines. Hainan
Hailing can expand registration and ensure equitable access of its antibiotics and antifungals listedon the 2021 WHO EML, such as cefepime and ceftazidime, to more countries, including low-income
countries. It can improve transparency on where its medicines are registered and made available.
Apply responsible sales practices for antibacterial and antifungal medicines. Hainan Hailing canapply responsible sales practices for antibacterial and antifungal medicines by not deploying sales
agents. Alternatively, it can fully decouple incentives for sales agents from sales volumes of such
medicines.

* All companies were assessed based ondata submitted to the Benchmark in thecurrent and previous periods of analysis, as well as information the companies have made publicly available, or thatare accessible through other sources.
For the 2021 Benchmark, Hainan
Hailing declined to submit data to the
Antimicrobial Resistance Benchmark.

153

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

HNH
Revenue by business segment

Therapeutic areas: Antifungal, Anti-infective, Angyomyocardiac, Anti-

2019

Data not disclosed

diabetics, Gastrointestinal, Nervous system

2020

Data not disclosed

Business segments: Pharmaceuticals
Product categories: Generic medicines
M&A since 2020: None in the antibacterial and/or antifungal sectors

HNH
Revenue by region
2019

Data not disclosed

2020

Data not disclosed

PORTFOLIO for pathogens in scope

HNH
Products on the market

Mid-sized portfolio: At least 43 products: 41 antibacterial medicines; 2 anti-

0fungal medicines

0

41 2
20

40

60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

Off-patent/generic medicines: 8 of 43 were selected for analysis** (amoxicillin [A], amoxicillin/clavulanic acid [A], caspofungin [F], cefepime [W],ceftazidime [W], faropenem [R], luliconazole [F], rifandine [T])AWaRe medicines***: 11 Access group; 25 Watch group; 1 Reserve groupAnti-TB medicines***: 1

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Hainan
Hailing is not evaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
No AMR-specific environmental

audits, whether conducted at its own sites, theties with cGMP at Hainan Hailing’s own sites or

risk-management strategy

sites of suppliers or external private and public

any subsidiaries.

Hainan Hailing states a general commitment

waste-treatment plants; (2) a list of these sup-to manufacture its products in an environmen-

pliers and plants; or (3) the limits and levels oftally responsible manner, supported by a dis-

antibacterial discharge from its own or suppli-

charge monitoring system to ensure complianceers’ sites.

with local regulations. It is unclear how the strategy takes AMR into account or aims to minimise

B.3

System in place to maintain production

the environmental impact of wastewaters andquality for own sites; limited information

solid waste from antibacterial manufacturing at

on suppliers; no requests for official cor-

its own sites, third-party suppliers of antibacte-rective action

rials or external private and public waste-treat-

Hainan Hailing reports that its own sites havement plants.

a system to maintain high-quality antibacterial
production consistent with international GMP

B.2

Limited publicly available information on

standards. There is limited information on audits,

environmental risk management

corrective actions and on how the company

Hainan Hailing publishes limited information

ensures that its suppliers uphold quality stand-on its approach to environmental risk-manage-

ards comparable to its own. The Benchmark

ment, without specific references to AMR. It

found no requests for official corrective action

does not publish: (1) the results of environmental

from the FDA or EMA related to non-conformi-** See Appendix VII for information about
eligibility criteria for products.
*** Listed on the 2019 WHO EML.

154

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries†
Hainan Hailing is not eligible for indicators: C.1.1,

C.2.2 No information on strategies to expand

C.1.3, C.2.1 and C.2.3 For more information, seeaccess to off-patent/generic medicines

Appendix VII.
C.1.2 No information on registration filings foroff-patent/generic medicines
Hainan Hailing’s performance is low, as it reports

C.3

No information on strategies to ensure
continuous supply

Hainan Hailing’s performance is low, as it dis-Hainan Hailing’s performance is low, as it dis-closes no information on how it expands accesscloses no information on how it ensures the con-to its eight relevant off-patent/generic med-tinuous supply of its relevant products to access

icines, beyond China. It does not provide evi-countries, beyond China.

dence of patient and geographic reach.

no evidence of filing its eight relevant off-patent/generic medicines for registration in accesscountries, beyond China.

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Educational Stewardship Activities

keting practices that aim to address the appro-

C.7

There is no information regarding Hainan

priate use of its antibacterial and/or antifun-

As a generic medicine manufacturer, Hainan

Hailing’s involvement in AMR-related educational

gal medicines as its marketing materials do not

Hailing is not assessed in this indicator nor does

programmes aimed at healthcare profession-reflect emerging resistance trends or include

it report any involvement in AMR surveillanceals and it is therefore not eligible for this indica-treatment guidelines for healthcare profes-

activities.

tor as there is no conflict of interest mitigation

sionals to raise awareness of AMR and address

to be assessed.

appropriate use.

C.5

C.6

Does not report sales or marketing practices that aim to address appropriate use

Hainan Hailing performs low in sales practices.

AMR Surveillance

Does not report adapting brochures and/or packaging to facilitate appropriate
use by patients

It does not report whether it decouples incen-

Hainan Hailing does not report adapting bro-tives for sales agents from sales volumes to help

chures and/or packaging to facilitate the appro-

prevent the inappropriate use of its antibacterial

priate use of its antibacterial and/or antifungal

and/or antifungal medicines.

medicines by patients.

Hainan Hailing does not report to engage in mar-

† 102 low- and middle-income countries
where better access to medicine is mostneeded.

155

Antimicrobial Resistance Benchmark 2021

SUN

Overall Performance
2020

11%

2021

47%▲

Access to Medicine Foundation

Sun Pharmaceutical Industries Ltd
Generic medicine manufacturer
Stock exchange: NSE • Ticker: SUNPHARMA • HQ: Mumbai, India • Employees: 36,000

SUN
PERFORMANCESun Pharma performs average overall in its evaluated Research Areas

Performance in the Benchmark

0%when compared to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Performs low. Reports a generalenvironmental risk-management strategy but without a specific aim to
limit AMR.
Appropriate Access: Middle-performing. Files its off-patent products inaccess countries. Discloses some strategies to expand access and ensure
continuous supply of its off-patent products.

conflict of interest mitigation for its educational programme. It adapts

/ 45
21/
50%

100%

Performance by Research Area
R&D

Points

0%

0/ 0

33%

Manufacturing

5/ 15

47%

Access

7/ 15

60%

Stewardship0%

Stewardship: Middle-performing. It does not report decoupling
incentives for sales agents from sales volumes. It reports comprehensive

Points47%

Overall score

9/ 15

50%

100%

How Sun Pharma was evaluatedbrochures and/or packaging for patients.
A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR SUN PHARMACHANGES SINCE 2020

Develop an AMR-specific environmental risk-management strategy and increase public disclo-

No changes are reported for Sun Pharma.

sure. Sun Pharma reports a commitment to manufacture its products in an environmentally responsible manner without specifying whether AMR is taken into account. It reports having one owned
manufacturing site, which employs Zero Liquid Discharge (ZLD) treatment processes. The company
can develop an AMR strategy for its own site and suppliers, based on the guidelines of the AMR
Industry Alliance. This includes setting limits and quantifying discharge levels to track compliance.
Sun Pharma can publish information on how it manages environmental risk related to antibacterial
manufacturing. The company publishes limited information about this.
Expand availability and ensure conitinuous supply of antibacterial and antifungal medicines tomore access countries. Sun Pharma can ensure equitable access and adequate supply of its antibiotics and antifungals listed on the 2021 WHO EML (e.g. the antifungal itraconazole and the reserve
antibiotic tigecycline) in more access countries. For example, Sun Pharma can ensure accurate
demand planning and data sharing, build on capacity or mitigate against shortages by working withseveral API suppliers.
Apply responsible sales practices for antibacterial and antifungal medicines. Sun Pharma canapply responsible sales practices for antibacterial and antifungal medicines by not deploying sales
agents. Alternatively, it can fully decouple incentives for sales agents from sales volumes of such
medicines.

156

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

SUN
Total income by business segment

Therapeutic areas: Anti-infectives, Cardiology, Dental, Dermatology,

2020*

Diabetology, Gastroenterology, Gynaecology, Nephrology, Neurology,

2021*

Nutritionals, Oncology, Ophthalmology, Orthopaedic, Psychiatry,

328,375
334,9810

Respiratory, Urology

100,000

200,000

400,000
mn INR*Financial year: April 2020 - March 2021

Pharmaceuticals

Business segments: Pharmaceuticals
Product categories: Consumer health products, Generic medicines,

SUN
Total income by region

Innovative medicines2020*

101,863

109,387

61,9732021*

109,498

103,564

64,053

M&A since 2020: None in the antibacterial and/or antifungal sectors

0
India

PORTFOLIO for pathogens in scope

300,000

100,000
United States

200,000

50,03054,277300,000

400,000
mn INR
Emerging markets
Rest of world*Financial year: April 2020 - March 2021

SUN
Products on the market

Mid-sized portfolio: At least 52 products: 44 antibacterial medicines; 8antifungal medicines
Off-patent/generic medicines: 8 of 52 were selected for analysis* (amoxi-

0
0

44
20

40

8
60

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

cillin [A], amoxicillin/clavulanic acid [A], ciprofloxacin [W], colistin [R], itraconazole [F], levofloxacin [W], nystatin [F], tigecycline [R])AWaRe medicines**: 9 Access group; 19 Watch group; 3 Reserve group

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Sun
Pharma is not evaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
No AMR-specific environmental risk
management strategy; ZLD at own site

B.2

Limited publicly available information on
environmental risk management

B.3

System in place to maintain production
quality for own sites; no requests forofficial corrective action

Sun Pharma reports a commitment to manufac-

Sun Pharma publishes limited information on its

ture its products in an environmentally responsi-

approach to environmental risk-management,

Sun Pharma publicly discloses that its own

ble manner, supported by a management system

without specific references to AMR. It pub-site has a system, including audits, to maintainthat includes periodic audits. It is unclear how

lishes that any manufacturing site that manu-

high-quality antibacterial production, consist-

the strategy takes AMR into account or aims tofactures antibiotics is qualified as ZLD. It does

ent with international GMP standards. It reports

minimise the environmental impact of waste-

not publish: (1) the results of environmental

auditing its suppliers on quality standards aswaters and solid waste from antibacterial man-audits, whether conducted at its own site, thewell. There is limited information on how correc-

ufacturing at its own site, third-party suppli-

sites of suppliers or external private and public

tive actions are implemented and tracked. The

ers of antibacterials or external private andwaste-treatment plants; (2) a list of these sup-Benchmark found no requests for official cor-public waste-treatment plants. Sun Pharma does

pliers and plants; or (3) the limits and levels ofrective action from the FDA or EMA related toreport that its sole site that manufactures anti-

antibacterial discharge from its own or suppli-

non-conformities with cGMP at Sun Pharma’s

bacterials is ZLD implying that no liquid waste isers’ sites.

own sites or any subsidiaries that manufacture

discharged into the environment from this site. It

antibacterials.

also reports that any antibacterial residue fromZLD is sent for incineration.

* See Appendix VII for information about
eligibility criteria for products.
** Listed on the 2019 WHO EML.

157

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Sun Pharma is not eligible for indicators: C.1.1,

low-income countries such as Chad, Nepal andtives. It mitigates against falsified and substand-C.1.3, C.2.1 and C.2.3. For more information, see

Syria. In 2020, Sun Pharma estimates to haveard medicines by reporting any suspicion ofAppendix VII.

provided access to its amoxicillin/clavulanic

counterfeit to the approriate regulatory author-

acid to 890,000 patients in 19 access countries,

ities. It uses a ‘Track and Trace’ technology toincluding Cameroon, Myanmar, and Peru.

prevent the sale of counterfeit medicines andC.1.2 Filed to register off-patent/generic medicines in 8 access countries on average
Sun Pharma has an average performance, filingto ensure the authenticity of its products. Sun
C.3

all its 8 relevant off-patent/generic medicines

Some strategies to ensure continuous

Pharma has a dedicated task force in place tosupplytrain filed forces to identify counterfeits.

for registration in 8 access countries on aver-

Sun Pharma has an average performanceage. Its most widely filed relevant product is thewith strategies reported in three of four areas

antibiotic amoxicillin/clavulanic acid filed in 22

assessed. It reports complying with good man-access countries. Four of its relevant products

ufacturing practices when producing API and

are filed for registration in at least one LIC.

drug products. Sun Pharma works towards product accessibility by ensuring regular supply of its

C.2.2 Some strategies to expand access to

products and having a robust distribution net-

off-patent/generic medicines

work in India, where it supplied its medicines to

Sun Pharma has an average performance. It

more than 500,000 pharmacies in urban andreports providing access to its antibiotics andrural areas in 2020. Sun Pharma does not report

antifungals to 45 access countries, of which

capacity building and technology transfer initia-C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

appropriate use of its antibacterial and/or anti-

C.7

in place for its educational programmes

fungal medicines as its marketing materials do

As a generic medicine manufacturer, Sun

Sun Pharma performs strongly in conflict of

not reflect emerging resistance trends or include

Pharma is not assessed in this indicator nor doesinterest (COI) mitigation for the five AMR-

treatment guidelines for healthcare profes-

it report any involvement in AMR surveillance

related educational programme for HCPs

sionals to raise awareness of AMR and address

activities.

assessed by the Benchmark. To mitigate COI

appropriate use.

AMR Surveillance

for all five programmes, it provides financial resources to independent third parties (DocMode, KOL International Academy,
Mediquest and Mindsync) to develop the
programmes.

C.6

Makes two types of brochure and/or packaging adaptations to facilitate
appropriate use by patients

Sun Pharma adapts brochures and/or packaging to facilitate the appropriate use of amoxicil-

C.5

Does not report sales or marketing prac-

lin/clavulanic acid by patients. Sun Pharma per-tices that aim to address appropriate use

forms well in this measure, taking account of

Sun Pharma performs low in sales practices. It

language and adherence to treatment. It has cre-does not report whether it decouples incentives

ated a QR code which directs to information on

for sales agents from sales volumes to help pre-how to take the product appropriately translated

vent the inappropriate use of its antibacterial

in ten regional languages in India. It also adapts

and/or antifungal medicines.

packaging to include information on AMR and

Sun Pharma does not report to engage in

how to take the product appropriately.

marketing practices that aim to address the*** 102 low- and middle-income countries where better access to medicine ismost needed.

158

Antimicrobial Resistance Benchmark 2021

TEV

Overall Performance
2020

2021

63% 60%▼Access to Medicine Foundation

Teva Pharmaceutical Industries Ltd
Generic medicine manufacturer
Stock exchange: NYSE • Ticker: TEVA • HQ: Petah Tikva, Israel • Employees: 40,216

TEV
PERFORMANCE

Performance in the Benchmark

Teva performs above average overall in its evaluated Research Areas0%

when compared to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Middle-performing. Reports environmental
risk-management strategy for own sites; tracks compliance with limits at
own sites.
Appropriate Access: Middle-performing. Files some of its relevant
products (off-patent generic medicines) for registration in accesscountries. Reports some strategies to expand access and ensure

Points60%

Overall score

/ 40
24/

50%

100%

Performance by Research Area
R&D

Points

0%

0/ 0

60%

Manufacturing

9/ 15

47%

Access

7/ 15

80%

Stewardship0%

continuous supply of its relevant product.
Stewardship: Performs well. It does not promote antibacterial and/or

50%

8/ 10
100%

How Teva was evaluatedantifungal medicines to healthcare professionals. It adapts packaging forpatients.

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR TEVACHANGES SINCE 2020

Ensure compliance with antibacterial discharge limits at suppliers sites by tracking and publicly• In its 2020 Environmental, Social anddisclosing progress and results specific to antibacterials for all sites. Teva can set limits and quan-

Governance (ESG) Progress Report, Teva pub-tify discharge levels to track compliance at all suppliers’s sites, as it does at its own sites, and pub-

licly commits to meet existing AMR Industry

licly disclose the results. Teva reports the goal to audit half of all supplier sites by end of 2030. Teva

Alliance commitments to minimise antimicro-

can also publish information on how it manages environmental risk related to antibacterial manu-bial discharges from its own operations andfacturing. The company currently publishes limited information.
Expand registration of antibacterial and antifungal medicines. Teva can expand registration of its
antibiotics and antifungals listed on the 2021 WHO EML, such as cefalexin, colistin and nystatin, to

supply chain by 2030.
• Teva pledged an unknown amount to the AMR
Action Fund

more countries, including low-income countries.
Ensure continuous supply of antibacterial and antifungal medicines. Teva mitigates against shortage risks, e.g., by maintaining a flexible safety stock management process and keeping buffer stocks.
It can implement several strategies to mitigate against shortage risks in access countries, e.g., build
local manufacturing capacity and transfer technology into access countries.
Expand adaptations to brochures and packaging to consider more patient needs. In order to support the appropriate use of its antibacterial and/or antifungal medicines by patients, Teva adapts
brochures to take account of local languages. It can further adapt its brochures and packaging to consider literacy levels, paediatric use, environmental conditions and patient adherence totreatment.

159

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONSTEVNet revenues by business segment

Therapeutic areas: Migraine/headache/pain, Neurodegenerative condi-

2019

tions and movement disorders, Oncology, Respiratory

2020

Business segments: North America, Europe, International Markets

8,447
0

Product categories: Biosimilars, Generic medicines, Innovative medicines
M&A since 2020: None in the antibacterial and/or antifungal sectors

8,542

2,246

4,757

2,154

10,000

North America

Europe20,000mn USDInternational Markets

TEV
Net revenues by region
2019

8,542

4,795

2,246

2020

8,447

4,757

2,154

0
North America

5,000

10,000EuropeInternational markets

PORTFOLIO for pathogens in scope

TEV
Products on the market

Comparatively large portfolio: At least 137 products: 115 antibacterial med-0

icines; 22 antifungal medicines

4,795

0

115
50

100

22
150

15,00020,000mn USD● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

Off-patent/generic medicines: 10 of 137 were selected for analysis*(amoxicillin [A], azithromycin [W], cefalexin [A], ciprofloxacin [W], clotrimazole [F], colistin [R], daptomycin [R], ethambutol [T], isoniazid [T],nystatin [F])AWaRe medicines**: 21 Access group; 43 Watch group; 5 Reserve groupAnti-TB medicines**: 4

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Teva is notevaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
Environmental risk-management for own

charge levels.

sites and plans implementation at sup-lished. Teva also does not publish: (1) the results

Teva expects external public and privateof environmental audits, whether conducted at

waste treatment plants to comply with its gen-its own sites, the sites of suppliers or external

Teva reports a strategy to minimise the environ-eral environmental standards. There is limited

private and public waste-treatment plants; or (2)mental impact of wastewaters and solid waste

information on the requirements Teva makes

a list of these suppliers and plants.

from antibacterial manufacturing at its sites,of external private and public waste-treatment

including audits every three years. It reports set-plants, in terms of audits and antibacterial dis-ting discharge limits in the receiving environ-charge limits and levels.

plier sites

B.3

System in place to maintain production
quality for own and suppliers’ sites; regulator requested official corrective action

ment for all antibacterials manufactured at its
Publicly discloses some information on

Teva reports that its own sites and suppliers

mended by the AMR Industry Alliance. Discharge

environmental risk management andhave a system to maintain high-quality antibac-

levels are quantified using a mass balance

quantifying discharge levels at own sites

terial production consistent with internationalsites, based on PNECs to limit AMR, as recom-

B.2

approach. It reports 22 of 32 sites have quanti-

Teva publishes some components of its envi-

GMP standards. This includes periodic risk-

fied discharge levels and 10, or 31%, are compli-

ronmental risk-management strategy. It is abased audits and tracking of corrective and pre-ant with discharge limits.

member of the AMR Industry Alliance, which

ventive actions. There is limited information on

publishes a list of recommended antibacte-

whether Teva requires its suppliers to audit theirers of antibacterials to follow similar standards.

rial discharge targets. Teva publicly commits to

own suppliers. In January 2020, an FDA drug

It reports a goal to audit 50% of all >250 suppli-quantifying discharge levels at 20 of its 34 own

quality inspection identified non-conformities

ers by the end of 2030.*** It does not yet requiresites that manufacture antimicrobials by the end

with cGMP at one Actavis site (a Teva subsidiary

suppliers to set discharge limits or quantify dis-of 2020.† The levels themselves are not pub-in Davie, FL, USA) producing antibacterial drug

Teva started requiring third-party suppli-* See Appendix VII for information about
eligibility criteria for products.
** Listed on the 2019 WHO EML.
***After period of analysis, Teva reported
that the number of suppliers is updated

to ~150.
†Discrepancy with number of sites in B.1 is

explained by Teva’s submission data for
the Benchmark being more up to datethan publicly available data.

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Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

products, resulting in an official request for corrective action. Teva reports that the oral antibacterial products manufactured at this site were
not impacted by the observations and that thesite is taking corrective actions.

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries‡
Teva is not eligible for indicators: C.1.1, C.1.3, C.2.1

access in access countries through donations

Planning (ERP) system. It reports keeping buffer

and C.2.3. For more information, see Appendix

and tenders. In 2020, Teva, together with its

stocks. Teva does not report capacity build-VII.

partners, reports having donated more than 17

ing and technology transfer initiatives. To mit-

mn units of antibiotics and antifungals to accessigate against substandard and falsified prod-

countries. In Malawi, Teva is partnering withucts, Teva directly donates its medicines to cer-

Global HOPE and Direct Relief, to donate anti-

tified partners and uses security features such as

Teva has an average performance, filing three of

biotics for pediatric immunosuppressed cancer

serialisation.

its 10 relevant off-patent/generic medicines forpatients. The initiative aims to treat 4,000 new

registration in three access countries on aver-patients in Malawi over the next five years. Teva

age. Its most widely filed relevant product isparticipates to the GDF and IDA Foundation

the antibacterial azithromycin, filed in 19 accessglobal tenders for tuberculosis, to provide line-

countries. Two of its relevant products are filed

zolid to all GDF eligible countries.

C.1.2 Filed to register off-patent/generic medicines in 3 access countries on averagein less than ten access countries. One of its relevant product (azithromycin) is filed for registra-

C.3

Some strategies to ensure continuous
supplytion in seven LICs.

Teva has an average performance, with stratC.2.2 Some strategies to expand access toegies reported in three of four areas assessed.

off-patent/generic medicines

Teva mitigates against shortage risks by main-

Teva has an average performance, with accesstaining a certain volume of products ready to

strategies reported for three of its ten relevant

donate. Teva has a flexible safety stock man-off-patent/generic medicines. It aims to expand

agement process within its Enterprise Resource

C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Educational Stewardship Activities

C.6

Makes one type of brochure and/or
packaging adaptation to facilitate appro-

There is no information regarding Teva’s involve-

priate use by patientsment in AMR-related educational programmes
aimed at healthcare professionals and it isTeva adapts packaging to facilitate the appro-

therefore not eligible for this indicator as there ispriate use of azithromycin, linezolid and pyri-no conflict of interest mitigation to be assessed.

doxine by patients. Teva is middle-performing inthis measure, taking account of language. The

C.5

Does not promote its antibacterial and/packaging contains information translated into

or antifungal medicines

English, Spanish, French and/or Portuguese.

Teva performs strongly in sales practices. It does
not deploy any sales agents to promote its anti-

C.7

bacterial and/or antifungal medicines to health-As a generic medicine manufacturer, Teva is notcare professionals. Since Teva does not develop

assessed in this indicator nor does it report any

or use marketing materials for antibacterial and/involvement in AMR surveillance activities.

AMR Surveillanceor antifungal medicines to promote such medicines to healthcare professionals, the company is not eligible to be assessed on marketing materials.

‡ 102 low- and middle-income countries
where better access to medicine is mostneeded.

161

Antimicrobial Resistance Benchmark 2021

VTR

Overall Performance
2020

2021

53% 67% ▲Access to Medicine Foundation

Viatris Inc
Generic medicine manufacturer
Stock exchange: NASDAQ • Ticker: VTRS • HQ: Canonsburg, PA, US • Employees: 45,000

VTR
PERFORMANCE
Viatris performs well overall in its evaluated Research Areas compared

Performance in the Benchmark

0%

to the other generic medicine manufacturers in scope.
Responsible Manufacturing: Performs well. Reports environmental riskmanagement strategy for own sites and suppliers; co-leads in reporting
compliance with limits at own sites.
Appropriate Access: Performs strongly. Files some of its on- and offpatent products for registration in access countries. Reports several
strategies to expand access and ensure continuous supply of its relevant

healthcare professionals, however it does not decouple sales incentives

R&D

adapt brochures or packaging for patients.

50%

100%

Points0%

0/ 0Manufacturing73%

11/ 15

Access72%

18/ 2553%

Stewardship
0%

8/ 15

50%

100%

How Viatris was evaluatedfrom sales volumes for its other products. It reports comprehensive
conflict of interest mitigation for its educational programmes. It does not

/ 55
37/

Performance by Research Area

products.
Stewardship: Middle-performing. It does not promote two products to

Points67%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR VIATRISCHANGES SINCE 2020

Ensure compliance with antibacterial discharge limits at suppliers’ sites by tracking and pub-Viatris was formed on November 16, 2020

licly disclosing progress and results specific to antibacterials for all sites. Viatris can set limits andthrough the combination of Mylan and Upjohn, aquantify discharge levels to track compliance at all suppliers’ sites and it can publicly disclose thelegacy division of Pfizer.

results. Viatris can also publish information on how it manages environmental risk related to antibacterial manufacturing. To provide clear evidence of its progress it can publicly report compliance at all sites. Disclosure of information, including the results of audits and antibacterial discharge
levels of its own sites and suppliers’ sites, is important. It can also publicly disclose the names andlocations of its suppliers and waste-treatment plants for increased transparency.
Improve accessibility of pretomanid (Dovprela) and delamanid (Deltyba®). Viatris filed delamanid (Deltyba®) and pretomanid (Dovprela) for registration in seven and 23 access countries. It can
expand the availability of these MDR-TB treatments by filing for registration in more access countries, in particular the countries with a high burden of MDR-TB identified by the WHO, where it hascommercialisation rights. Accessibility can be improved through public/private partnerships, patient
assistance programmes and donations.
Expand registration of generic antibacterial and antifungal medicines. Viatris can expand registration of its generic antibiotics and antifungals listed on the 2021 WHO EML, such as linezolid, polymyxin B, and amphotericin b, to more countries, including low-income countries.
Fully decouple incentives for sales agents from sales volumes. Viatris does not promote pretomanid (Dovprela) and flucytosine. Viatris can expand this practice to all antibacterial and antifungal
medicines. Alternatively, it can fully decouple incentives for sales agents from sales volumes of all
antibacterial and antifungal medicines.
Adapt brochures and packaging. In order to support the appropriate use of its antibacterial and/or antifungal medicines by patients, Viatris can adapts its brochures and packaging to consider
local languages, literacy levels, paediatric use, environmental conditions and patient adherence totreatment.

162

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONSVTR
Revenue by business segment

Therapeutic areas: Cardiovascular, CNS and anesthesia, Dermatology,

2019

Diabetes and metabolism, Gastroenterology, Immunology, Infectious dis-2020

ease, Oncology, Respiratory and allergy, Women’s healthcare.

M&A since 2020: Viatris was formed on November 16, 2020 through the

2,000

4,000

1,723

1,195

8,000

130

1,854

10,000Emerging Markets
Other

126

12,000mn USDVTR
Revenue by region

combination of Mylan and Upjohn, a legacy division of Pfizer.

2019

8,240

2020

8,511
0

1,723
1,854

5,000

Developed markets
Greater China

PORTFOLIO for pathogens in scope

6,000

Developed Markets
Greater China
JANZ

markets

1,193

8,511
0

Business segments: Developed Markets, Greater China, JANZ, Emerging
Product categories: Biosimilars, Generic medicines, Innovative medicines

8,240

10,000JANZ
Emerging markets

15,000Other

20,000mn USDVTR
Products on the market

Comparatively large portfolio: At least 87 products: 72 antibacterial medicines; 15 antifungal medicines

00On-patent medicines: 2 (delamanid, pretomanid)

72
20

40

60

15
80

100

120

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

Off-patent/generic medicines: 9 of 85 were selected for analysis* (amoxicillin [A], amoxicillin/clavulanic acid [A], amphotericin b [F], flucytosine [F],isoniazid [T], linezolid [T], piperacillin/tazobactam [W], polymyxin B [R],vancomycin [W])AWaRe medicines**: 24 Access group; 34 Watch group; 1 Reserve groupAnti-TB medicines**: 5

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT

As a generic medicine manufacturer, Viatris is
not evaluated in this Research Area.

B
B.1

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)
Environmental risk-management for own

also requests and reviews the discharge levels ofor external private and public waste-treatmentsites and suppliers; tracks compliance

its suppliers as part of these audits. It is unclear

plants; (2) a list of these suppliers and plants; orwith limits at own sites

how many of the 35 suppliers are assessed so(3) the levels of antibacterial discharge from its

far and have quantified discharge levels.

own or suppliers’ sites.

Viatris reports a strategy to minimise the environmental impact of wastewaters and solid

There is limited information on the require-

waste from antibacterial manufacturing at its

ments Viatris makes of external private andsites, including audits every five years. It reports

public waste-treatment plants, in terms of strat-

setting discharge limits in the receiving environ-egy, audits and antibacterial discharge limits andment for all antibacterials manufactured at its

levels.

B.3

System in place to maintain production
quality for own and suppliers’ sites; norequests for official corrective action

Viatris reports that its own sites and suppliers

sites, based on PNECs to limit AMR, as recom-

have a system to maintain high-quality antibacPublicly discloses some information on

terial production consistent with international

levels are quantified at all sites using a mass

environmental risk management and

GMP standards. This includes periodic risk-balance approach. All its sites, or 100%, arequantifying discharge levels at own sites

based audits and tracking of corrective and pre-mended by the AMR Industry Alliance. Discharge

B.2

reported to be compliant with discharge limits.

Viatris publishes some components of its envi-

ventive actions. Viatris also requires its suppli-

It reports that eight of its sites that manufac-

ronmental risk-management strategy. It is a

ers to audit their own suppliers. The Benchmark

ture antibacterials are ZLD and that recycled

member of the AMR Industry Alliance, whichfound no requests for official corrective action

water was analysed for presence of antibacteri-

publishes a list of recommended antibacterial

from the FDA or EMA related to non-conformi-

als which was found to be zero.

discharge targets. Viatris publishes its commit-

ties with cGMP at Viatris’ own sites or any sub-ment to setting these targets. It also publicly dis-sidiaries that manufacture antibacterials.

Viatris requires third-party suppliers of antibacterials to follow the same standards, includ-

closes that all of its own sites have quantified

ing limits based on PNECs. It engaged with

antibacterial discharge levels. It does not publish:

EcoVadis to start an audit programme among its(1) the results of environmental audits, whether

top 35 antibiotic suppliers to assess AMR risk. It

conducted at its own sites, the sites of suppliers* See Appendix VII for information about
eligibility criteria for products.
** Listed on the 2019 WHO EML.

163

Antimicrobial Resistance Benchmark 2021

C

Access to Medicine Foundation

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Viatris is not eligible for indicators: C.1.3 andto its on-patent medicines in access coun-ings and supply reviews. Viatris mitigates against

C.2.3. For more information, see Appendix VII.

tries through public/private partnerships, dona-

shortage risks by keeping buffer stocks and con-tions, tenders and a named patient access pro-ducting supplier audits. It registers several of

Filed to register on-patent medicines ingramme. Viatris partners with the GDF–Stop TB

its products at multiple production sites, includ-15 access countries on averagePartnership to provide pretomanid at a global

ing in China, South Africa, and Zambia, ensuring

Viatris performs above average, filing its two rel-access price of USD 364 per treatment course

geographical diversification and dual sourcing.

evant on-patent medicines for registration in

to 150 countries. Viatris provides evidence ofViatris estimates 50% of its main products’ APIs

access countries. Its most widely filed relevant

patient reach and geographic reach for all its

or finished forms to be dually sourced. To miti-

product is the anti-tuberculosis medicine preto-

reported approaches. In 2019 and 2020, it pro-gate against sub-standard and falsified products,

manid, filed in 23 access countries, including fivevided 6,000 treatment courses of delamanid

Viatris has a dedicated infrastructure to moni-

LICs. Under its licensing agreement with Otsuka,

through a government tender in South Africa.

tor product safety and manage related efforts.

C.1.1

Viatris filed delamanid for registration in sevenThis includes, but is not restricted to, a prodC.2.2 Some strategies to expand access to

uct portfolio risk assessment process, analy-

off-patent/generic medicines

sis and market monitoring, a suspicious order

Viatris has an average performance. It reports

monitoring programme, and a product diversion

that it aims to expand access to its off-patent/

programme that includes anonymous report-

Viatris has an average performance, filing seven

generic medicines in access countries throughing mechanisms and a supplier code of conduct.

of its nine sample off-patent/generic medicines

equitable pricing and public/private partner-

Viatris uses security features such as serialisa-

for registration in seven access countries on

ships. For example, Viatris partnered withtion or 2D data matrix.

average. Its most widely filed relevant productstakeholders such as UNITAID, CHAI, and theis vancomycin, filed in 15 access countries. Six

Global Fund to provide flucytosine, prior toof its sample products are filed in less than 10

WHO-prequalification.

access countries.
C.1.2 Filed to register off-patent/generic medicines in 7 access countries on average

access countries. Five of its sample products are
filed for registration in at least one LIC.

C.3

Several strategies to ensure continuous

C.2.1 Several strategies to expand access to

Viatris performs above average, with strate-

supplyon-patent medicines

gies reported in all four areas assessed. Viatris

Viatris performs above average, with accessensures accurate demand planning and data

strategies reported for both its two relevant

sharing by having a 24-months horizon planningon-patent medicines. It aims to expand accessand daily, weekly, or monthly operational meet-C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

inappropriate use of such medicines.

share results in a peer-reviewed medical jour-in place for its educational programmes

Viatris does not report to engage in market-

Viatris performs strongly in conflict of interesting practices that aim to address the appropriate

Pretomanid Resistance Surveillance Program,(COI) mitigation for the five AMR-related edu-

use of its antibacterial and/or antifungal med-

which is focused on resistance against pretoma-

cational programmes for HCPs assessed by theicines as its marketing materials do not reflect

nid in eight countries until 2025. Once data col-Benchmark. To mitigate COI for one programme,

emerging resistance trends or include treatment

lection has been completed, Viatris intends toit provides financial resources to an independ-

guidelines for healthcare professionals to raise

share data with regulatory authorities and in aent third party (Omnicuris), which collaborated

awareness of AMR and address appropriate use.

peer-reviewed journal article.

nal. Moreover, Viatris runs the multinationalwith another independent organisation (ISCCM)
to develop the programme. The remaining four

C.6

Does not report adapting brochures and/or packaging to facilitate appropriate

programmes have all three COI mitigation strat-

use by patientsegies looked for by the Benchmark: (1) content
is developed independently from its marketing

Viatris does not report adapting brochures and/department; (2) a pledge not to provide financial

or packaging to facilitate the appropriate use ofor material incentives; and (3) it does not use

its antibacterial and/or antifungal medicines bybranded materials.

patients.

C.5

Engages in sales practices but does not

C.7

engage in marketing practices to address

As a generic medicine manufacturer, Viatris

appropriate use

is not assessed in this indicator but its activ-

AMR Surveillance

Viatris performs above average in sales prac-

ities in AMR surveillance are reported. The

tices. It does not deploy any sales agents to pro-Benchmark notes that Viatris is active in two

mote pretomanid and flucytosine to healthcare

AMR surveillance programmes. It supports theprofessionals. However, for the remaining anti-

national Data Development programme, which

bacterial and/or antifungal medicines it does not

is a retrospective study of antimicrobial resist-

report whether it decouples incentives for sales

ance in ICU patients in India and has been run-agents from sales volumes to help prevent thening since 2019. Viatris reports that it intends to*** 102 low- and middle-income countries where better access to medicine ismost needed.

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Antimicrobial Resistance Benchmark 2021

Appendices166

Appendix I: Analysis, scoring and review process

169

Appendix II: Limitations

170

Appendix III: Scoring guidelines

177

Appendix IV: Identifying best practices

178

Appendix V: Priority pathogens included
for analysis in R&D

179

Appendix VI: Access countries

180

Appendix VII: Appropriate Access:Product Scope and Definitions

181

Appendix VIII: Guide to Report Cards

185

Appendix IX: Figures

186

Appendix X: Definitions

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Antimicrobial Resistance Benchmark 2021

APPE N D IX I

Analysis, scoring and review process
PRO CESS FO R ANTI M I CRO B IAL

gle-INN components but with different doses inprojects up until 30 April 2021 (when the data

PO RTFO LI O ANALYS I S

one or more of the components, were consid-

collection period ended), with two exceptions:ered equivalent and aggregated. The Benchmark(1) for R&D indicators, the status of R&D pro-

The product portfolio database, including

also considered that different salts of the same

jects was monitored between 30 April 2021

medicines and vaccines, was constructed using

single-INN product or FDC component wereand 24 September 2021 and R&D products

information from various sources, including pro-considered equivalent and aggregated. On theapproved up to 24 September 2021 wereprietary data from IQVIA, public sources fromother hand, product modifications that resulted

included as approved products in the reportpharmaceutical companies and supplemented

in significantly different chemical/pharmaceuti-

cards. Of note, (1) no additional R&D projects(where relevant) with data from company sub-cal properties were considered non-equivalentor changes of phase happening after 30 April

missions. The Benchmark requested the compa-

to the original product (examples include ben-

2021 were accounted for in the analysis; (2) for

nies in scope to review, verify and provide addi-

zathine benzylpenicillin, a type of benzylpenicil-

stewardship indicators, such as C.4 and C.7, pro-tional data on their antibacterial and antifungallin). The Benchmark also considered that com-grammes active at some point during the period

portfolio for analysis. Companies were asked tobination products differing only in components

of analysis were included, regardless of theirlist each of their antibacterial or antifungal prod-that are not antimicrobials were equivalent andending date. Financial data from fiscal years

ucts’ International Nonproprietary Name (INN)

hence aggregated. Lastly, co-packaging of two

2019 and 2020 was used for analysis (the exact

and brand name(s).

products already marketed by a company (sin-date marking the fiscal year end varies amonggle-INN or FDC) did not count as an additional

companies).

All products on the market as of 30 April 2021
(when the data collection period ended) were

product. For the analysis combining companies’

eligible for inclusion in the descriptive analysis of

portfolios (in the portfolio analysis section of

Data review

the product portfolio. The research team verified

this report) no further data aggregation tookCompanies were asked to verify the accuracy ofwhether R&D projects included for analysis inplace, meaning a product with a given INN, mar-publicly sourced data and to provide additional

the R&D Research Area were approved between

keted by more than one company, was counted

necessary information. Prior to analysis, thethe date of submission and until 30 April 2021. If

as many times as the number of companies that

Benchmark team reviewed companies’ submis-

approved between those dates, the product wasmarket it. The purpose of this was to provide

sions for each of the Research Areas:

included in the company’s pipeline. R&D pro-an overview of the antibacterial and antifungal

Research & Development: R&D projects con-jects with market approval dates after the end

market.

sisting of antibacterial and antifungal medi-of the period of analysis on 30 April 2021 andInformation regarding whether or not thecines and vaccines were included for the over-until 24 September 2021 (the time period during

product was listed on the WHO Model List of

all pipeline. R&D projects eligible for scoring

which the status of R&D projects was moni-

Essential Medicines (EML) was also verified by

had to target at least one of the pre-defined

tored by the Benchmark) were not added to thethe research team. This final product portfolio,

priority pathogens (see Appendix V). R&D pro-company’s marketed product portfolio. In someincluding 1521 products, was compared to thejects were classified as innovative or adapted.

instances, companies did not submit their entire

21st WHO EML, published in 2019, to assess the

Adapted R&D projects do not involve a new

antibacterial and antifungal portfolio during thenumber of products on this list. For a productchemical or biological entity (NCE or NBE);

data collection period. Products not submitted

to be considered by the Benchmark as a part ofinnovative R&D projects involve either an NCE

may include products with different INNs as wellthe EML, the INN, the specific formulation andor NBE. New medicines in clinical develop-

as products with the same INN but marketed

strength had to be listed on the EML (chap-

ment were further classified as novel when

under different brand names (e.g. in different

ter 6 anti-infectives and chapter 19.3 vaccines).

they fulfilled one or more of the following

countries/regions). For companies that did not

Antibacterial medicines on the EML were further

criteria, defined by WHO in its 2020 analy-

participate in the Benchmark’s survey, the ini-grouped according to the Access, Watch andsis of the antibacterial clinical and preclinicaltially pre-populated database was used for all

Reserve (AWaRe) classification. Antituberculosis

development pipeline¹: (a) it represents a new

descriptive product portfolio analyses.

medicines were classified as: antituberculo-

chemical class; (b) it aims at a new target; (c)To ensure products were within scope and eli-sis medicines. Products that could be linked toit has a new mode of action; (d) it displays nogible for analysis – i.e. antibacterial and antifun-

an EML product via a Square box were treatedcross-resistance with existing antimicrobials.

gal medicines and vaccines for human use, boththe same way as products that were mentioned

After final submission and any necessary clari-systemic and topical– and that there were noon the EML and all alternatives listed were also

fications with the companies, all R&D projects

duplicate products within a company’s submis-

included in the product portfolio database.

were evaluated according to a standardised

sion, the research team reviewed and validated
companies’ submitted portfolios. For analyses atprocedure.
SU M MARY O F TH E SCO R I N G PRO CESS

the individual company level, product data was

Responsible Manufacturing: the Benchmark

aggregated at the INN level, since these wereCompanies were assessed and scored by therequested companies to share their policies

used to showcase the different active antibac-

Benchmark in three Research Areas: Researchon the manufacturing of antibacterial APIs andterial and antifungal ingredients that the com-

& Development, Responsible Manufacturing anddrug products. Information on environmen-

pany marketed (formulations, doses, routes ofAppropriate Access and Stewardship, with eachtal risk management was requested for com-administration or brand names were not differ-area composed of several indicators. Due to thepany's own sites, suppliers’ sites and external

entiated). INN-level aggregation was performed

variation between companies in scope, not all

private and public waste treatment plants. The

both in the case of products with a single INN

indicators were applicable to every company, as

Benchmark further requested whether any ofand fixed-dose combinations (FDCs) composed

shown in the Indicators and Scoring Eligibility

the sites or plants set limits on antibacterialof two or more single-INN elements – there-

table in this Appendix.

discharge and quantified the discharge levels

fore, two FDCs containing, e.g., the same sin-

The Benchmark included ongoing/active

to determine compliance with limits. The qual-

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Antimicrobial Resistance Benchmark 2021

ity of manufacturing was evaluated for not justa wide range of information sources including

drug products but also APIs at the sites of thecompany verification, independent reports andcompany's own and suppliers’ sites. Any GMP

databases or documents from WHO, other mul-

non-conformities at manufacturing sites weretilateral organisations and Non-Governmental

identified by reviewing public databases ofOrganisations. For currency conversion to USD,

the FDA and EMA. For transparency indicatorexchange rates on the website x-rates.com were

B.2, the research team reviewed companies’

used.

public information on, e.g., corporate websites,

Final scoring of the companies was the result

annual reports and corporate social responsi-

of a multi-tiered analysis and quality assurance

bility reports.

process. The quality assurance process included
both systematic verification of scoring con-Appropriate Access: the Benchmark

sistency and spot-checking. For each indicator,

requested companies to share their accesspreliminary scoring results were used to makeand stewardship policies for antibacterials andadjustments in scoring guidelines to ensure max-

antifungals for the Research Area on Access,imum variability of final results.

specifically the indicators Registration (C.1.1,
C.1.2, C.1.3) and Expanding Access (C.2.1, C.2.2.,

Review process

C.2.3.). The Benchmark examined on- andFollowing clarification and cross-check of com-

off-patent medicines and vaccines separately.

pany scores, the research team wrote the var-

The on-patent antibacterial and antifungal

ious sections of the Benchmark report. Eachmedicines and vaccines were derived from the

Research Area was reviewed by at least one

product portfolio as described above and were

externally appointed expert advisors. In addi-

verified by the companies The selection oftion to this, an external editorial review of theoff-patent products (antibacterial and antifun-

Benchmark report was performed.

gal medicines) was based on each company’s
two highest volume sales data globally and in

M E TH O D O LO GY D E VE LO PM E NT

21 low-income markets, which were provided
by IQVIA Midas® based on sales data fromTo develop the methodology for the 2021

2017. These products were derived from the

Antimicrobial Resistance Benchmark, the2019 EML and were divided into six catego-

Foundation applied its proven process for build-ries. Three categories were based on the 2019

ing consensus on the role of pharmaceutical

WHO AWaRe Classification of Access, Watch,companies in tackling global health priorities.

and Reserve and two categories were forStrategic guidance was provided by an Expert

Antifungal and Anti-Tuberculosis medicines.

Committee for the Benchmark, an independent

Companies’ policies and strategies for thesebody of experts, from top-level academic cen-on- and off patent medicines and vaccinestres, donor governments, local governments inwere then analysed in the various access-re-low- and middle-income countries, investors, andlated indicators.

companies. The Expert Committee met in July
2020 to review proposals for the scope, struc-Stewardship: up to five: (a) educational stew-

ture, and analytical approach of the Benchmark.

ardship activities; (b) AMR surveillance pro-

Their recommendations helped identify ways

grammes; and (c) stewardship-oriented adap-

forward where disagreement or uncertainty

tations for patients were evaluated by theexisted regarding areas of research.

Benchmark for each company. In addition,
the Benchmark evaluated sales and market-

The Expert Committee members

ing practices that aim to address the appro-

Hans Hogerzeil (Chair)

priate use of the company’s antibacterial and

Gregory Frankantifungal medicines. Finally, the Benchmark

Sudarshan Jain

collected data around general AMR education

Joakim Larsson

for patients and the sharing of consumption

Marc Mendelson

data with public health authorities for report-

Mirfin Mpundu

ing purposes.

Maria Larsson Ortino
Sarah Paulin (Observer)

Scoring
All indicators were scored from zero to five andStakeholders by groupweighted equally. When scoring a company on

Discussions were held with representatives of aa quantitative indicator, such as financial invest-

wide range of organisations, a list of which canments or R&D pipeline size, the corresponding

be found in the methodology report for the 2021

number was first scaled across all companies in

Antimicrobial Resistance Benchmark, available

scope for scoring.

for download at www.amrbenchmark.org.

When a given indicator was not applicable toa company, the company’s maximum attainable
score in the corresponding Research Area wasdecreased by an amount equal to the number ofmaximum points attainable in that indicator.
Scoring was carried out based on data from

1. WHO. (2021). 2020 antibacterial agents in clinical andpreclinical development: an overview and analysis.
Retrieved from: https://www.who.int/publications/i/
item/9789240021303

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I N D I C ATO RS AN D SCO R I N G E LI G I B I LIT Y

IN SCOPE FOR R&D

FOR RMA1 A2.1 A2.2 A2.3 A2.4 A3

IN SCOPE FOR AA

FOR STW

B1

B2

B3 C1.1 C1.2 C1.3 C2.1 C2.2 C2.3 C3

C4

C5

C6

C7

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Cipla

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Fresenius Kabi

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Sun Pharma

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Teva

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Generic medicine manufacturers

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Large research-based pharmaceutical

off-patent/generic medicines were eligible

companies were eligible for scoring in every

for indicators C.1.2 and C.2.2. All companies

research area, with a few exceptions. Generic

supplying on-patent antibacterial and antifungal

medicine manufacturers were eligible for

vaccines were eligible for indicators C.1.3 andscoring in the RM, AA and STW research

C.2.3. In line with the external stakeholder

areas but not in R&D, as their main focus isconsensus defined by the Foundation, genericthe manufacturing of generic products. Large

medicine manufacturers were not eligible forresearch-based pharmaceutical companies andscoring in indicator C.7 AMR Surveillance as theygeneric medicines manufacturers were eligible

have thus far had a limited role in such activities.

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to specific Appropriate Access indicators basedon the products in their respective portfolio: allcompanies supplying on-patent antibacterial
and antifungal medicines were eligible forindicators C.1.1 and C.2.1. All companies supplying

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APPE N D IX I I

Limitations
In this section we cover the main limitations

priority pathogen in phase II or more advanced

information on discovery and preclinical stage

faced in the Benchmark. All limitations, method-of clinical development and with an anti-infec-

projects was often obtained from company sub-ological, process or otherwise will be reviewed

tive product portfolio. Generic medicine manu-

missions. Both sets of information were usedby the Foundation when undertaking future

facturers were also selected based on whether

for analysis and scoring. Hence, the comprehen-

Benchmarks.

they are a large vendor of active pharmaceuticalsiveness and level of detail available in publicingredients (APIs). The Benchmark findings onsources and in the data submitted by the compa-

G E N E R AL M E TH O D O LO G I C AL

this category of companies should therefore benies are thus limiting factors in the Benchmark

LI M ITATI O N S

taken in this context.

analysis. Furthermore, some information was

Depending on the research area being ana-

submitted by companies on the basis of confi-

As in any survey, main limitations relate to cover-lysed, different company types might be included

dentiality, thus making the Benchmark’s ability

age, sampling, non-responder and measurementin the analysis. For instance, within the R&D

to analyse and report conclusions across several

biases. To the extent possible, the Benchmark

research area, indicators on the pipeline areindicators challenging.

research team worked to minimise the impact

applicable to large research-based pharmaceuti-of these biases in the final results. On cover-cal companies but not to generic medicine man-age and representativeness, we attempted toufacturers. Both company types are quite differ-ensure that coverage of our survey represented

ent with vastly different business models. In theas much as possible the wider antimicrobial

Benchmark analysis, we adjusted for these var-industry players with relevant activities acrossiations between company types, company size,

the three Research Areas. The criteria used toand company portfolio whenever relevant andselect companies for the Benchmark is out-

possible. Further, the Benchmark provides key

lined in detail in our Methodology Report 2020.

information about companies’ antibacterial andCompanies are sometimes unwilling or unable toantifungal business in several sections of thedisclose data, or, if they do, may do so only par-report, which readers should take into accounttially. For example, the content of R&D projects

as important context when interpreting theand pricing information may be treated more

Benchmark findings.

cautiously by companies.

Different factors may affect companies’
capacity for reporting information. Some companies have submitted only a selection of their

APPLI C AB I LIT Y O F FI N D I N GS

antibacterial and antifungal business to the
Benchmark. Hence, the data presented in the

Disease and product scopes“Portfolio Analysis” section of this report and on

The outputs analysed in this study and the The

individual company report cards may not nec-

outputs analysed in this study and the findings

essarily represent their entire portfolio result-generated from it relate only to the disease anding in a potential underreporting of the number

product scopes as outlined in the Antimicrobialof essential medicines on the 2019 WHO EML.

Resistance Benchmark Methodology 2020. The

Different companies also use different nomen-

2021 Benchmark will focus on bacterial andclature and have different ways of categorising

fungal infections, particularly those identified as

information. For example, when calculating theparticular threats due to resistance, called pri-value of antibacterial and antifungal R&D invest-

ority pathogens, as determined by WHO andments or revenue from antibacterial and antifun-

the CDC for the R&D research area. For thegal sales, such disaggregated data might not be

Responsible Manufacturing research area, thereadily available. In an effort to minimise variabil-

focus through stakeholder and expert review

ity in interpretation and ensure data consistency,

committee consensus was to focus on compa-

a glossary of definitions was published in the

ny’s initiatives and activities around antibacterial

Benchmark Methodology Report 2020.

APIs and drug products. The Appropriate Accessresearch area assessed included companies’

Data Availability

antibacterial and antifungal medicines and vac-

As in all survey methodologies, the data of thecines. The Stewardship research area assessed

Benchmark is dependent on company sub-antibacterial and antifungal medicines.

missions as the source data as well as on data
available in the public domain. To mitigate any

Company comparability

reporting bias and for scoring purposes, every

Among the large research-based pharmaceuti-

effort was made to triangulate company-submit-

cal companies and generic medicine manufac-

ted data by verifying it against public sources,

turers, companies were selected based on theirsuch as company annual reports, WHO reports,

antibacterial sales volume or value of their sales.

and clinical trial registries. Insofar triangulation

Large research-based pharmaceutical com-

was not possible, data submitted by the com-panies were also selected for their antibacte-panies was used for scoring. For example, in the

rial pipelines that have at least one antibacte-

R&D research area, while clinical stage projects

rial medicine or vaccine candidate targeting a

could be verified with publicly available data,

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APPE N D IX I I IScoring guidelinesA

RESEARCH & DEVELOPMENT

A .1

R& D I NV E STM E NTS
R&D investments (including in-kind) dedicated to the development of antibacterial and antifungal medicines andvaccines targeting pathogens in scope during fiscal years 2019 and 2020.
3-5 The percentage of the company’s revenue derived from pharmaceuticals (and vaccines if activein vaccine development) that it then invests (spends) in the development of antibacterial and/or
antifungal medicines and/or vaccines targeting pathogens in scope.​
This number is scaled across all companies that disclose their investments.
2

The company invests in R&D and it does not disclose. The company also pledges funds to the
AMR Action Fund or it supports AMR R&D indirectly with considerable funds.

1

The company does not invest in-house in R&D AMR projects, but it pledges funds to the AMR
Action Fund or it supports AMR R&D indirectly with considerable funds.

0

The company does not invest in the development of antibacterial and antifungal medicines andvaccines for medicines in scope directly or indirectly.

N/A Generic medicine manufacturers are not scored in this indicator.
A . 2 .1

PI PE LI N E S I Z E
The size of a company’s R&D pipeline targeting priority pathogens, including antibacterial and antifungal medicines andvaccines (new chemical/biological entities and adaptations) developed in-house or through collaborations.
1-5

The sum of medicines and vaccines projects in development, or having received approval during
the period of analysis, that target pathogens in scope.​
This number is scaled across all companies and scored.

0

The company has no relevant R&D activity within the scope of this indicator.

N/A Generic medicine manufacturers are not scored in this indicator.
A.2.2

N OVE LT Y O F PI PE LI N E
The novelty of new investigational clinical antibacterial and antifungal medicines targeting priority pathogens that thecompany is developing (in-house or through collaborations). A new product candidate in development is defined as
containing at least one new component (entity) not previously approved.
5

The company has more than 1 innovative medicine project in clinical development described in
the WHO’s ‘Antibacterial agents in clinical and preclinical development’ as fulfilling any of the innovativeness criteria.

4

The company has at least 1 innovative medicine project in clinical development described in the
WHO’s ‘Antibacterial agents in clinical and preclinical development’ as fulfilling any of the innovativeness criteria.​Criteria is extended to antifungals.

3

The company has more than one innovative medicine project in clinical development.

2

The company has at least 1 innovative medicine project in clinical development.

1

The company has only adaptive projects in clinical development.

N/A The company does not have any medicine project in clinical development.
Generic medicine manufacturers are not scored in this indicator.
A.2.3

VACCI N ES I N TH E PI PE LI N E
The number of vaccines that the company is developing for priority pathogens in scope (in-house or throughcollaborations).
5

The company has a large vaccine pipeline, (n ≥ 10), mostly focused on new projects that contain atleast one new biological component (entity) not previously approved.

4

The company has a medium-sized vaccine pipeline, (n ≥ 5 to n < 10), mostly focused on new projects that contain at least one new biological component (entity) not previously approved.

3

The company has a small vaccine pipeline, (n < 5), and at least half (≥50%) of the pipeline isfocused on new projects that contain at least one new biological component (entity) not previously approved.

2

The company has a small vaccine pipeline, (n < 5), and at least half (≥50%) of the pipeline isfocused on adaptive projects (i.e. projects that do not include a new biological entity).

N/A The company is not engaged in vaccine development and therefore has no relevant​R&D activity
within the scope of this indicator.
Generic medicine manufacturers are not scored in this indicator.

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A . 2 .4

PROJ EC TS TARG E TI N G CR ITI C AL PR I O R ITI ES
The number of projects that target a ‘critical’ pathogen (as defined by WHO) and/or ‘urgent’ pathogen (as defined by
the CDC). These pathogens include carbapenem-resistant (CR) Acinetobacter spp., C. auris, C. difficile, CR or ESBLproducing Enterobacteriaceae, drug-resistant N. gonorrhoeae and CR P. aeruginosa.
5

The company has 8 or more projects with unique candidates/combinations targeting critical/
urgent priorities.

4

The company between 4 and 7 projects with unique candidates/combinations targeting critical/
urgent priorities.

3

The company has 3 projects with unique candidates/combinations targeting critical/urgent
priorities.

2

The company has 2 projects with unique candidates/combinations targeting critical/urgent
priorities.

1

The company has 1 project targeting critical/urgent priorities

0

The company does not have projects targeting critical/urgent priorities.

N/A Generic medicine manufacturers are not scored in this indicator.
A.3

ACCESS AN D STE WAR DS H I P PL AN N I N G
The proportion of late-stage antibacterial and antifungal R&D projects targeting priority pathogens, for which thecompany provides information about having plans in place for 1) access in countries in scope and where burden of disease is higher; and 2) stewardship on a global scale. This indicator applies to late-stage R&D projects in Phase II and III
of clinical development (developed in-house or through collaborations) and recently approved products.
5

The company has a large late-stage pipeline with comprehensive portfolio-wide policies and project-specific access and stewardship (as applicable) plans for all relevant projects. Plans include
clear access-oriented policies across the company’s portfolio with elements such as the intention
to file for registration in ‘access countries’, ensuring the breadth of access components incorporate considerations for affordability and supply, engaging in surveillance, and using evidence fromlocal patterns of disease and/or resistance to inform all activities.

4"The company has comprehensive and project-specific access and stewardship (as applicable) plans for all late-stage medicines and vaccines.
OR
The company has a large late-stage pipeline with company-wide access and stewardship commitments and some project-specific plans that reflect the company’s access-oriented intentions."

3

The company has project-specific access and stewardship (as applicable) plans in place for all of
its late-stage projects.

2

The company has at least one late-stage project with a project-specific access (for medicines andvaccines) and/or stewardship (for medicines) plan.

1

The company has general commitments or policies in place to develop access and/or​stewardship plans for late-stage R&D projects, but the company provides no clear evidence of such plans
being applied to existing late-stage R&D candidates.

0

The company reports having neither access nor stewardship plans or commitments for its latestage R&D candidates.

N/A The company does not have any late-stage projects and is therefore not in scope for this indicator.
Generic medicine manufacturers are not scored in this indicator.
B
B .1

RESPONSIBLE MANUFACTURING
E NVI RO N M E NTAL R I S K- MANAG E M E NT STR ATEGY
The company has an environmental risk-management (ERM) strategy to minimise the environmental impact of manufacturing discharge of antibacterials that includes:(i) implementation of waste-treatment practices for both liquid and solid antibacterial-containing wastes taking AMR
risk into account(ii) on-site auditing of compliance with the strategy(iii) setting of antibacterial discharge limits based on predicted no-effect concentrations (PNECs) for resistance selection(iv) monitoring/quantification of the levels of antibacterials discharged in wastewaters to assess and manage risk that
limits are surpassed
The points above apply to the company’s:(a) owned and/or operated manufacturing sites(b) third-party suppliers of antibacterial active pharmaceutical ingredients (APIs) and/or drug products(c) external privately-owned* or public waste-treatment plants
Elements (i) to (iv) define the depth of the strategy and elements (a) to (c) define its breadth. There are a total of
12 elements, corresponding to the 12 combinations of 4 depth elements with 3 breadth elements. In the case ofwaste-treatment plants, depth elements (iii) and (iv) were merged for the scoring process, resulting in a maximum
total of 11 elements assessed by the Benchmark. Each element was considered fully, partially or not met and assigned
1, 0.5 or 0 points, respectively. Points were summed to obtain the final score. Some elements were not applicable to allcompanies which was accounted for in final scoring.

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5

The company demonstrates an ERM strategy that covers 8.5 or more of the applicableindicator elements.

4

The company demonstrates an ERM strategy that covers 7-8 of the applicable indicator elements.

3

The company demonstrates an ERM strategy that covers 5-6.5 of the applicable indicator elements.

2

The company demonstrates an ERM strategy that covers 3-4.5 of the applicable indicator elements.

1

The company demonstrates an ERM strategy that covers 0.5-2.5 of the applicable indicator elements.

0

The company demonstrates an ERM strategy that covers 0 of the applicable indicator elements.
* Off-site plants that are more than 50% owned by private parties, which may or may not include
the company itself.

B.2

D I SCLOSU R E O N E NVI RO N M E NTAL R I S K MANAG E M E NT
The company publishes the following elements:(a) components of its ERM strategy to minimise environmental impact of wastewaters and solid waste from antibacterial manufacturing(b) results of strategy audits at the company’s manufacturing sites, third-party sites manufacturing antibacterial APIs
and drug products and/or external private waste-treatment plants(c) identities of third parties manufacturing antibacterial APIs and drug products and/or of external private
waste-treatment plants(d) levels (concentrations) of antibacterial discharge and discharge monitoring/quantification(e) limits set for antibacterial discharge, along with methodological and evidential bases*.
5

The company publishes 5 of the 5 indicator elements.

4

The company publishes 4 of the 5 indicator elements.

3

The company publishes 3 of the 5 indicator elements.

2

The company publishes 2 of the 5 indicator elements.

1

The company publishes 1 of the 5 indicator elements.

0

The Benchmark found none of the indicator elements published in the company’s website,annual report, or CSR/EHS reports.
* Discharge limits published on the AMR Industry Alliance website were also considered
for this element in the 2021 Benchmark, despite not qualifying as disclosure via an official individual company source.

B.3

MAN U FAC TU R I N G H I G H - Q UALIT Y ANTI BAC TE R IAL S
The company makes commitments, has systems in place and promotes initiatives to ensure, maintain and/or improve
the production of high-quality antibacterial APIs and drug products at its own and suppliers' manufacturing sites, in amanner consistent with the international standards developed and accepted by recognised national and international
authorities.
To accomplish this, the company reports having a quality system that meets the following five elements:(1) it is consistent with international standards such as FDA, EU and/or WHO Good Manufacturing Practice (GMP) at all
own and/or suppliers' sites.
(2) it includes quality monitoring procedures at own and suppliers' sites, e.g. periodic auditing(3) it includes a system for implementation and tracking of corrective and preventive actions at own and suppliers'
sites(4) it includes a requirement of its suppliers in scope to conduct periodic on-site audits of their own suppliers' sites(5) the authorities above, as applicable, have not publicly reported GMP non-conformities at companies’ own sites orsites of wholly-owned direct subsidiaries, during the period of analysis
Regarding the fourth element, after publication of the Methodology on 06 October 2020, this element was added tothe scoring process to assure high-quality manufacturing deeper into the supply chain.
Regarding the fifth element, the Benchmark considered non-conformities* to be either (a) inspections with a resultof ‘Official Action Indicated’ (OAI) as made publicly available in the FDA’s Inspection Classification Database underthe ‘Drug Quality Assurance’ project area, or (b) non-compliance reports found in the EMA EudraGMP database, bothreferring to inspections with end date within the period of analysis, 22 June 2019 to 30 April 2021, inclusive. Databases
were last consulted on 22 October 2021.
5

The company reports having a quality system that meets 5 of the 5 indicator elements.

4

The company reports having a quality system that meets 4 of the 5 indicator elements.

3

The company reports having a quality system that meets 3 of the 5 indicator elements.

2

The company reports having a quality system that meets 2 of the 5 indicator elements.

1

The company reports having a quality system that meets 1 of the 5 indicator elements.

0

The company demonstrates no information on a quality system that meets any of the 5
indicator elements.
* It was sometimes not possible to determine whether the sites affected by non-conformities produced antibacterials. Such non-conformities were nevertheless taken into
account in the Benchmark assessment, since they suggest potential risks regarding how
the companies’ reported quality system (usually covering all sites) is being implemented
at sites producing antibacterials.

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C
C .1 .1

APPROPRIATE ACCESSR EG I STR ATI O N O F O N - PATE NT ANTI BAC TE R IAL AN D ANTI FU N GAL M E D I CI N ES
Companies are assessed according to the average number of access countries in which on-patent antibacterial andantifungal medicines have been filed for registration.
5

The company files its on-patent medicines for registration in >40 access countries on average.

4

The company files its on-patent medicines for registration in 11-40 access countries on average.

3

The company files its on-patent medicines for registration in 6-10 access countries on average.

2

The company files its on-patent medicines for registration in 1-5 access countries on average.

1

The company has on-patent medicines that have been filed in at least one access country, but files
them in less than one access country on average or there is little information available.

0
C .1 . 2

The company has on-patent medicines, but there is no evidence of filing in access countries.

R EG I STR ATI O N O F O FF- PATE NT/G E N E R I C ANTI BAC TE R IAL AN D ANTI FU N GAL PRO D U C TS
Companies are assessed according to the average number of access countries in which eligible off-patent/generic antibacterial, antifungal, and anti-tuberculosis medicines have been filed for registration.
5

The company files its eligible off-patent products for registration in >40 access countries on
average.

4

The company files its eligible off-patent products for registration in 11-40 access countries on
average.

3

The company files its eligible off-patent products for registration in 6-10 access countries on
average.

2

The company files its eligible off-patent products for registration in 1-5 access countries on
average.

1

The company has eligible off-patent products that have been filed in at least one access country,
but files them in less than one access country on average or there is little information available.

0

The company has eligible off-patent products, but there is no evidence of filing in accesscountries.

C .1 . 3

R EG I STR ATI O N O F O N - PATE NT ANTI BAC TE R IAL AN D ANTI FU N GAL VACCI N ES
Companies are assessed according to the average number of access countries in which on-patent antibacterial andantifungal vaccines have been filed for registration.
5

The company files its on-patent vaccines for registration in >40 access countries on average.

4

The company files its on-patent vaccines for registration in 11-40 access countries on average.

3

The company files its on-patent vaccines for registration in 6-10 access countries on average.

2

The company files its on-patent vaccines for registration in 1-5 access countries on average.

1

The company has on-patent vaccines that have been filed in at least one access country, but files
them in less than one access country on average or there is little information available.

0
C . 2 .1

The company has on-patent vaccines, but there is no evidence of filing in access countries.

E XPAN D I N G ACCESS TO O N - PATE NT ANTI BAC TE R IAL AN D ANTI FU N GAL M E D I CI N ES
Companies are assessed on the access strategies they use to expand access to and ensure affordability of their on-patent antibacterial and antifungal medicines in access countries. Each access strategy reported by a company is assessedagainst five main elements:(a) Access strategy: the company reports a clear, well-described, and detailed access strategy, either at product level
or on a wider scale.
(b) Pricing strategy: the company considers ability to pay when setting the price of its on-patent medicines and indicates what factors are taken into account to address ability to pay (e.g., socio-economic and/or demographic factors).
(c) Evidence of geographic reach: the company reports on the geographic scope of its access strategy.
(d) Evidence of patient reach: the company reports on the number of patients reached by its access strategy in accesscountries.
(e) Acknowledgment of access needs and commitment to expand access: the company acknowledges the accessneeds in access countries and demonstrates commitment to expand access to its on-patent medicines to more people
in more countries.
1-5

Each of the five elements was assigned between 0 and 2 points.
The points were summed, and the total was brought to a score out of 5 to get the final score.
For example, the company received a maximum score of 5 if it met all the above elements: the company takes a proactive approach and demonstrates willingness to reach more
people with its medicines in access countries, including those with a high disease burden. The
company uses and combines a range of strategies. Access strategies are clear, well described,
and detailed – specifying patient reach and geographic reach, and considering ability to
pay where appropriate.

0

The company reports no evidence of providing access to its on-patent medicines inaccess countries.

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C.2.2

E XPAN D I N G ACCESS TO O FF- PATE NT/G E N E R I C ANTI BAC TE R IAL AN D ANTI FU N GAL PRO D U C TS
Companies are assessed on the access strategies they use to expand access to their eligible off-patent/generic medicines in access countries. Each access strategy reported by a company is assessed against four main elements:(a) Access strategy: the company reports a clear, well-described, and detailed access strategy, either at product level
or on a wider scale.
(b) Evidence of geographic reach: the company reports on the geographic scope of its access strategy.
(c) Evidence of patient reach: the company reports on the number of patients reached by its access strategy in accesscountries.
(d) Acknowledgment of access needs and commitment to expand access: the company acknowledges the accessneeds in access countries and demonstrates commitment to expand access to its off-patent/generic medicines tomore people in more countries.
1-5

Each of the five elements was assigned between 0 and 2 points. The points were summed, andthe total was brought to a score out of 5 to get the final score.
For example, the company received a maximum score of 5 if it met all the above elements: thecompany takes a proactive approach and demonstrates willingness to reach more people with its
medicines in access countries, including those with a high disease burden. The company uses andcombines a range of strategies. Access strategies are clear, well described, and detailed – specifying patient reach and geographic reach.

0

The company reports no evidence of providing access to its off-patent/generic products
in access countries.

C.2.3

E XPAN D I N G ACCESS TO O N - PATE NT ANTI BAC TE R IAL AN D ANTI FU N GAL VACCI N ES
Companies are assessed on the access strategies they use to expand access to and ensure affordability of their on-patent antibacterial and antifungal vaccines in access countries. Each access strategy reported by a company is assessedagainst five main elements:(a) Access strategy: the company reports a clear, well-described, and detailed access strategy, either at product level
or on a wider scale.
(b) Pricing strategy: the company considers ability to pay when setting the price of its on-patent vaccines and indicateswhat factors are taken into account to address ability to pay (e.g., socio-economic and/or demographic factors).
(c) Evidence of geographic reach: the company reports on the geographic scope of its access strategy.
(d) Evidence of patient reach: the company reports on the number of patients reached by its access strategy in accesscountries.
(e) Acknowledgment of access needs and commitment to expand access: the company acknowledges the accessneeds in access countries and demonstrates commitment to expand access to its on-patent vaccines to more people inmore countries.
1-5

Each of the five elements was assigned between 0 and 2 points. The points were summed, andthe total was brought to a score out of 5 to get the final score.
For example, the company received the maximum score of 5 if it met all the above elements: thecompany takes a proactive approach and demonstrates willingness to reach more people with its
medicines in access countries, including those with a high disease burden. The company uses andcombines a range of strategies. Access strategies are clear, well described, and detailed – specifying patient reach and geographic reach, and considering ability to pay where appropriate.

0
C.3

The company reports no evidence of providing access to its on-patent vaccines in access countries.

E N SU R I N G CO NTI N U O US SU PPLY
Companies are assessed according to four main elements representing areas they can engage in to ensure the continuous supply of their products: demand planning and data sharing, shortage mitigation, capacity building and technology
transfers and substandard and falsified medicines mitigation.
(a) Demand planning and data sharing: The company ensures accurate demand planning and data sharing, including thestakeholders and the frequency with which it informs them about its demand plans.
(b) Shortage mitigation strategies: The company employs strategies to mitigate shortage risks including whether there
is a buffer stock; whether the company audits its stock; whether there is a dedicated task force to manage the supply
chain and prevent shortages; and whether the company promotes API supplier diversity, including risk mitigation forAPIs with single suppliers.
(c) Capacity Building and technology transfers: The company promotes capacity building and technology transfer initiatives for the manufacturing of antibacterial and antifungal products, mentioning where these initiatives are implemented and demonstrating how they strengthen supply chain in the access countries.
(d) Substandard and falsified medicines mitigation: The company employs strategies to mitigate the circulation of substandard and falsified medicines.
1-5

Each of the four elements was assigned between 0 and 7 points. The points were summed, andthe total was brought to a score out of 5 to get the final score.

0

The company reports no evidence of ensuring the continuous supply of its medicines or vaccines
in access countries.

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C
C .4

STEWARDSHIPE D U C ATI O NAL STE WAR DS H I P AC TIVITI ES
The company has a clear strategy to ensure that any conflict of interest (COI) is mitigated in its (support of) antibacterial and antifungal stewardship educational activities directed at healthcare professionals. To mitigate COI, the company provides an unrestricted grant to an independent third party to develop the educational activity, or if it is developed in-house, the company ensures COI is mitigated through an independent review of the educational activity by athird party such as an accreditation body.
5

The company engages in AMR-related educational programmes aimed at healthcare professionals (HCPs) with comprehensive conflict of interest (COI) mitigation* for all of its programmes (upto five programmes total).

4

The company engages in AMR-related educational programmes aimed at HCPs with comprehensive COI mitigation* for the majority (more than half) of its programmes (up to five programmes
total).

3

The company engages in AMR-related educational programmes aimed at HCPs with comprehensive COI mitigation* for the minority (less than half) of its programmes (up to five programmes
total).
OR
The company engages in AMR-related educational programmes aimed at HCPs with some COI
mitigation for its programmes (up to five programmes total). Some COI mitigation refers toincluding any of the three of the Benchmark’s defined COI mitigation strategies.**0

The company engages in AMR-related educational programmes aimed at HCPs without any COI
mitigation.

N/A The company does not engage in AMR-related educational programmes aimed at HCPs and istherefore not eligible for assessment of COI mitigation for such programmes.
* Comprehensive COI mitigation can be done either by:(1) providing an unrestricted grant to an independent third party to develop the programme; or(2) if developed in-house, ensuring an independent evaluation of the programme (e.g. by receiving
accreditation or by a review committee);or(3) implementing all three of the Benchmark’s defined COI mitigation strategies.**** The three COI mitigation strategies are: (a) ensuring that the content and speaker selection
is independent from the marketing department; (b) pledging not to provide financial or material
incentives to participants; and (c) ensuring there are no branded products or materials in the content of the programme.
C.5

R ES PO N S I B LE PRO M OTI O NAL PR AC TI CESResponsible promotional practices when engaging with healthcare professionals include sales practices that aim toavoid overselling of antibacterials and antifungals by either not promoting such products or by decoupling incentives
for sales agents from sales volumes. In addition, the company adapts its marketing materials to include AMR trends
and guidelines for healthcare professionals.
5• The company does not promote any of its antibacterial and/or antifungal medicines to healthcare professionals (e.g. by not deploying sales agents or by only participating in tenders for thesales of such medicines).
• The company fully decouples incentives for sales agents from sales volumes for all of its antibacterial and/or antifungal medicines AND reflects emerging resistance trends and/or treatment
guidelines for healthcare professionals (HCPs) in its marketing materials. Full decoupling means
there is no variable pay in sales agents’ total pay linked to sales volumes.

4

The company reflects emerging resistance trends and/or treatment guidelines for HCPs in its
marketing materials AND fulfils at least one of the following points:• The company does not promote at least one antibacterial and/or antifungal medicine OR does
not promote such medicines in some geographies to HCPs (e.g. by not deploying sales agents orby only participating in tenders for the sales of such medicines).
• The company fully decouples incentives for sales agents from sales volumes for at least one
antibacterial and/or antifungal medicine OR fully decouples incentives for sales agents fromsales volumes for such medicines in some geographies. Full decoupling means there is no variable pay in sales agents’ total pay linked to sales volumes.
• The company partly decouples incentives for sales agents from sales volumes for 98% and for allof its antibacterial and/or antifungal medicines in all geographies. Partial decoupling means (partof) the variable pay in sales agents’ total pay is based on sales volumes.

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3

• The company reflects emerging resistance trends and/or treatment guidelines for HCPs in its
marketing materials.
• The company does not promote at least one antibacterial and/or antifungal medicine OR does
not promote such medicines in some geographies to HCPs (e.g. by not deploying sales agents orby only participating in tenders for the sales of such medicines).
• The company fully decouples incentives for sales agents from sales volumes for at least one
antibacterial and/or antifungal medicine OR fully decouples incentives for sales agents fromsales volumes for such medicines in some geographies. Full decoupling means there is no variable pay in sales agents’ total pay linked to sales volumes.
• The company partly decouples incentives for sales agents from sales volumes for all of its antibacterial and/or antifungal medicines in all geographies. Partial decoupling means (part of) the
variable pay in sales agents’ total pay is based on sales volumes.

0

The company does not report engaging in practices that aim to address the appropriate use of
its antibacterial and/or antifungal medicines, either regarding its sales practices or its marketing
materials.
Bullet points refer to OR situations.

C .6

STE WAR DS H I P - O R I E NTE D ADAPTATI O N S FO R PATI E NTS
The company adapts its brochures and/or its packaging to facilitate the appropriate use of antibacterial and antifungal
products by patients. The company considers the needs of the patient population, including language, literacy, and paediatric use (if relevant). In addition, the company aims to improve adherence to treatment and considers local environmental conditions to preserve the effectiveness.
5

The company adapts its brochures and/or packaging to take account of all patient needs: language, literacy levels, paediatric use*, adherence to treatment and environmental conditions.

4

The company adapts its brochures and/or packaging to take account of at least two patientneeds: language, literacy levels, paediatric use*, adherence to treatment and/or environmental
conditions.

3

The company adapts its brochures and/or packaging to take account of only one patient need:language, literacy levels, paediatric use*, adherence to treatment or environmental conditions.

0

The company does not adapt its brochures and/or packaging to facilitate the appropriate use of
its antibacterial and/or antifungal medicines by patients.

N/A The company only sells antibacterial and/or antifungal medicines that are administered by healthcare professionals rather than by patients and is therefore not eligible for assessment of adaptations to facilitate appropriate use by patients.
* Adaptations for paediatric use are only assessed if the company has any products in its portfolio for paediatric use.
C .7

AM R SU RVE I LL AN CE
The company has, supports, and/or contributes to antibacterial and antifungal surveillance programmes to track resistance to pathogens, and shares such data publicly.
5

The company publicly shares* raw data of at least one AMR surveillance programme.

4

The company shares raw data of at least one AMR surveillance programme on a data platform in a
restricted manner.

3

The company publicly shares* aggregated results of at least one AMR surveillance programme.

2

The company does not publicly share* raw data or aggregated results of its AMR surveillance
programme(s).

0The company does not report any involvement in AMR surveillance programmes.

N/A The company is involved in AMR surveillance programme(s) but its data collection is not yet completed and is therefore not eligible for data sharing.
Generic medicine manufacturers are not assessed in this indicator as they have a limited role in
AMR surveillance activities.
* Publicly sharing surveillance data can be done through open-access data platforms or peer-reviewed open-access journal articles.

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APPE N D IX IV

Identifying best practices
The diffusion of best practices is one of the

PRO CESS

Benchmark’s mechanisms for supporting
the pharmaceutical industry in curbing AMR.

To determine which of the company’s prac-

Recognising those companies piloting or scal-

tices would be highlighted as best practice, theing up unique industry policies or initiatives is an

Foundation’s research team evaluated all aspects

important way of acknowledging those compa-

of company practices, compiling those that met

nies prepared to stand out from peers.

the criteria used for the purpose of scoring withadditional standards for each Research Area,

B EST PR AC TI CE S

where necessary. Practices that met these outlined criteria were reviewed and finalised by theBest practices are ones that can be accepted

Foundation’s senior management with additionalas being the most effective way of achieving a

input from experts in the corresponding field,

desired end, relative to what the industry is cur-when required.

rently doing in that area and what stakeholder
expectations are. It can also be described as abenchmark. Best practices are not new practices– they have already been conceived of, appliedand proven to meet at least some of the following criteria:• Sustainability;• Replicability;• Alignment with external standards/stakeholder expectations;• Proven effectiveness.
In different areas of analysis (for example, in
Research & Development vs. in Appropriate
Access) how a best practice is identified may
be different. A best practice need not be uniqueamongst companies. A best practice might bean example of a ‘gold standard’ of practice; abest-in-class policy; or a strategy, programme,
product initiative or group of behaviours closelyaligned with stakeholder expectations. Bestpractices should be considered as the exemplar of positive practices in the corresponding research area in comparison to those of theother companies that submitted data within thecurrent period of analysis. These best practices
are identified based on evidence of progress
submitted in the data collection period and verified with public information and through consultation with experts, where appropriate.

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APPE N D IX V

Priority pathogens included for analysis in R&D
In the Research & Development Research Area, the Benchmark will assess

Indicator A.2.4 of the Benchmark will assess companies’ projects targetingthe size and public health value of a company’s pipeline of investigational

the most critical priorities in these lists, i.e. targeting the pathogens classi-

antibacterial and antifungal medicines and vaccines. The disease scope

fied by the CDC and WHO as “Urgent” or “Critical”, respectively.

for the 2021 AMR Benchmark includes the pathogens, with their specificresistance profiles, from the priority pathogens lists published by World
Health Organization (WHO)1 and the Centers for Disease Control andPrevention (CDC)2 (see full list below).

Pathogen

WHO Priority List1

Resistance profile

CriticalCarbapenem

CDC Biggest Threats2

Resistance profile

BAC TE R IA
Acinetobacter spp.
Bordetella pertussis
Campylobacter spp.

High

Fluoroquinolones

Clostridioides difficile
Enterobacteriaceae*

UrgentCarbapenem

Watch

Drug-resistantSerious

Drug-resistantUrgentCriticalCarbapenem

UrgentCarbapenem

Extended-Spectrum

Serious

Extended-Spectrum

ß-Lactamase (ESBL)Enterococcus faecium

High

Vancomycin (VRE)

Haemophilius influenzae type b (Hib)

Medium

Ampicillin

Helicobacter pylori

High

Clarithromycin

Mycobacterium tuberculosis

R&D priority

Enterococcus spp.

Serious

Mycoplasma genitalium
Neisseria gonorrhoeae

ß-Lactamase (ESBL)High

Cephalosporins

Vancomycin (VRE)

Serious

Drug-resistant

Watch

Drug-resistantUrgentDrug-resistantSeriousMultidrug-resistantFluoroquinolones
Pseudomonas aeruginosa

CriticalCarbapenem

Salmonella spp.

High

Fluoroquinolones(MDR)
Salmonella non-typhoidal &Serious

Drug-resistant

serotype typhi
Shigella spp.

MediumFluoroquinolones

Serious

Drug-resistant

Staphylococcus aureus

High

Methicillin

Serious

Methicillin (MRSA)

Vancomycinintermediate andresistant
Streptococcus (group A)

Concerning

Erythromycin

Streptococcus (group B)

Concerning

Clindamycin

Serious

Drug-resistantAzole-resistant

Streptococcus pneumoniae

MediumPenicillin-nonsusceptible

FU N G I
Aspergillus fumigatus

Watch

Candida auris

UrgentCandida spp.

SeriousR E FE R E N CE S
1 WHO. (2017). Global priority list of antibiotic-resistant bacteria to guideresearch, discovery, and development of new antibiotics.
2 U.S. Centers for Disease Control and Prevention (CDC). (December2019). Antibiotic resistance threats in the United States, 2019.

Drug-resistant* Enterobacteriaceae has been renamed to Enterobacterales.

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APPE N D IX VI

Access countries
List of countries covered by access metrics forthe 2021 Antimicrobial Resistance Benchmark –102 countries

E A ST A S IA & PACI FI C

Honduras

LMIC

Congo, Dem. Rep.

Cambodia

LMIC

MexicoHIDBCCongo, Rep.

China

HIDBC

Nicaragua

LMIC

Côte d’Ivoire

LMIC

Indonesia

LMIC

Paraguay

HIHDC

Equatorial Guinea

MHDC

Kiribati

LMIC

Peru

HIDBC

Eritrea

Suriname

HIHDC

Ethiopia

Korea, Dem. People’s Rep.

LIC

LIC
LMIC

LIC
LIC

Lao PDR

LMIC

Micronesia, Fed. Sts.

LMIC

M I D D LE E A ST & N O RTH AFR I C A

Gambia, The

Mongolia

LMIC

Djibouti

LMIC

Ghana

Myanmar

LMIC

Egypt, Arab Rep.

LMIC

GuineaLIC

Papua New Guinea

LMIC

Iraq		

MHDC

Guinea-Bissau

LIC

Philippines

LMIC

Morocco

LMIC

Kenya

LMIC

Solomon Islands

LMIC

Syrian Arab Republic

LIC

Lesotho

LMIC

Thailand

HIDBC

Tunisia

LMIC

Liberia

LIC

Timor-Leste

LMIC

Palestine, State /Madagascar

LIC

TuvaluLDC

West Bank and Gaza

LMIC

Malawi

LIC

Vanuatu

LMIC

Yemen, Rep.

LIC

Mali

Vietnam

LMIC

Gabon

Mauritania
SO UTH A S IAE U RO PE & CE NTR AL A S IA

Afghanistan

Georgia

LMIC

KosovoLMIC

Kyrgyz Republic

LMIC

Moldova

LMIC
LIC

Tajikistan

Mozambique

HIHDC
LIC
LMIC

LIC
LMIC
LIC

LIC

Namibia

Bangladesh

LMIC

Niger

LIC

BhutanLMIC

Nigeria

LMIC

India

LMIC

RwandaMaldives

HIHDC

São Tomé and Príncipe

MHDC

LIC
LMIC

Nepal

LIC

SenegalLIC

Turkmenistan

HIHDC

Pakistan

LMIC

Sierra Leone

LIC

UkraineLMIC

Sri Lanka

LMIC

Somalia

Uzbekistan

LMIC

South Africa
SU B -SAHAR AN AFR I C ASouth Sudan

LIC
MHDC
LIC

L ATI N AM E R I C A & C AR I B B E AN

AngolaBelize

HIHDC

Benin

Bolivia, Plurinat. State

LMIC

Botswana

BrazilHIHDC

Burkina Faso

LIC

Togo

LIC

Colombia

HIHDC

BurundiLIC

UgandaLIC

Dominican Republic

HIHDC

Cabo Verde

LMIC

ZambiaLMICEl Salvador

LMIC

Cameroon

LMIC

Zimbabwe

Guatemala

MHDC

Central African Republic

LIC

Guyana

MHDC

Chad

LIC

Comoros

LIC

Haiti

LIC

LMIC

Sudan

LMIC

LIC

Swaziland

LMIC

HIHDC

Tanzania

LIC

LIC

Table legend
LIC		

Low-income country, World Bank income classifications (June 2018)

LMIC

Lower middle-income country, World Bank income classifications (June 2018)

LDC

Least Developed Country, UN ECOSOC LDC list (March 2018)

LHDC

Low Human Development Country, UNDP Human Development Indices and Indicators (September 2018)

MHDC

Medium Human Development Country, UNDP Human Development Indices and Indicators (September 2018)

HIHDC

High Inequality in Human Development Country, UNDP Human Development Indices and Indicators (September 2018)

HIDBC

High Infectious Disease Burden Country, IHME Global Burden of Disease Study 2017 Results

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APPE N D IX VI I

Appropriate Access: Product Scope and Definitions
PRO D U C T SCO PE AN D E LI G I B LE

DonationsTiered Pricing Policy

I N D I C ATO RS[Working definition, used for analysis][Working definition, used for analysis]

A short- or long-term donation of products

Tiered pricing, also known as differential pric-

based on the expressed needs of a country.

ing, refers to when differing classes of buyers are

Donations may be made in emergency situations,charged different prices for the same product. In• Top 2 off -patent products by sales volume

such as conflict and natural disasters, or may be

the context of vaccines, low-and middle-income

within each appropriate access category

longer-term to control or eradicate a disease.

countries can be charged a reduced price com-

• On-patent antibacterial and antifungal medicines – eligible indicators: C.1.1 - C.2.1.

– eligible indicators: C.1.2 – C.2.2.
•A ppropriate Access Categories: WHO

pared to high-income countries2.
Patient Assistance Programme

AWaRe classification, tuberculosis medi-[Working definition, used for analysis]

Voluntary Licensing

cines and antifungals.

Patient assistance programmes are defined as[Working definition, used for analysis]• [A]=Access group, [W]=Watch group,

programmes initiated by pharmaceutical compa-

A voluntary license is an authorisation given by[R]=Reserve group, [T]=tuberculosis,

nies which provide financial assistance or free-of

the patent holder to a generic company, allowing[F]=antifungal.

charge medicines for a defined patient popula-

it to produce the patented medicine or vaccine,tion with limited ability to pay.

often at a lower cost. The license usually sets

• On-patent antibacterial and antifungal vaccines – eligible indicators: C.1.3 - C.2.3.
• All products were analysed by INN.

quality requirements and defines the countries in
Pooled-Procurement

which the licensee can sell the product3.

[Working definition, used for analysis]
D E FI N ITI O N S

Pooled procurement is the formal arrangement

Direct Sales Contract

where financial and nonfinancial resources are[Working definition, used for analysis]

Access strategy

combined across different purchasing authori-

A direct sales contract is an agreement between[Working definition, used for analysis]ties to create a single entity for purchasing med-a pharmaceutical company and a buyer. The

A strategy specifically intended to improveicines or vaccines on behalf of individual pur-pharmaceutical company agrees to supply its

access to medicines or vaccines, that includes allchasing authorities. Pooled procurement can

medicines or vaccines to the buyer at a spec-

the typical elements of a strategy (a clear ration-

be managed through a third-party such as theified price. The contract may be for a specificale, targets, objectives and expected outcomes).

United Nations Children’s Fund (UNICEF), Stop

volume or for a specific contract period. Direct

In low- and middle-income countries where the

TB Partnership Global Drug Facility or the Pan

sales are often used by generic manufacturers

company operates, the strategy may apply to a

American Health Organization (PAHO)1.

to expand access to their generic medicines, anddefined set of diseases, products, or therapeuticareas or to the whole portfolio.

the buyers may be, but are not limited to, distribPrice Cap

utors or hospitals in the public or private sector.

[Working definition, used for analysis]
Affordability

A price cap or price ceiling is a maximum price[Working definition, used for analysis]that can be charged for a product. A price cap is

The measure of a payer’s ability to pay for ausually negotiated between a government andproduct (whether or not they are the end user).

a pharmaceutical company to take affordability

The Benchmark takes this into account when

into account.

assessing pharmaceutical companies’ pricing
strategies.

Public-Private Partnership[Working definition, used for analysis]

Patient Reach

A public-private partnership (PPP) is a partner-[Working definition, used for analysis]

ship between one or more public organisations

The Benchmark evaluates the impact of com-and the private sector for providing a publicpanies’ access strategies by looking for evi-

asset or service, in which the private party bears

dence of patient reach. Patient reach is defined

significant risk and management responsibil-

by number of people benefitting from a specificity, and remuneration is linked to performance.

access strategy or by the number of product

The Benchmark also considers a partnership

units distributed.

between a non-profit organisation and the private sector to be a PPP.

Equitable Pricing Policy

R E FE R E N CE S

[Working definition, used for analysis]

Tender

A targeted pricing strategy, which aims at[Working definition, used for analysis]

improving access to medicines and vaccines for

A tender is a competitive procurement proce-those in need by taking affordability for individ-

dure to supply medicines or vaccines. The ten-uals and healthcare systems into account in adering process typically comprises price andmanner that is locally appropriate.

volume requirements and is commonly used inmany countries to encourage competition, particularly in lower-income countries or international agencies procuring on behalf of lower-income countries.1

1WHO. WHO Guideline on Country Pharmaceutical
Policies.; 2020. Accessed October 14, 2021. file:///C:/
Users/Diane/Downloads/9789240011878-eng.pdf
2 The World Bank and GAVI Alliance. Immunization
Financing Toolkit.; 2010. Accessed October 14, 2021.
https://www.who.int/immunization/programmes_systems/financing/analyses/Brief_14_Tiered_Pricing.pdf
3 IFPMA. Voluntary licenses and non-assert declarations. Published online 2010. Accessed October
14, 2021. https://www.ifpma.org/resource-centre/
voluntary-licenses-and-non-assert-declarations/180

Antimicrobial Resistance Benchmark 2021

APPE N D IX VI I I

Guide to Report Cards
The Guide to Report Cards provides a description of each section of theReport Cards for the 2021 Antimicrobial Resistance Benchmark.

SectionDescription

SourceGeneral company information

Company name, Stock exchange(s), Ticker(s), Location of•	Annual report for the fiscal year ending 31(header)headquarters, Number of employees (as a total)

December 2020 or later (or, equivalently,
forms 10-K or 20-F)• Company website

Performance in the Benchmark

This figure shows the company’s overall score.

• Benchmark analysis

This figure shows the company’s score for each of the Research Areas• Benchmark analysis(figure)Performance by Research Area

in which it was scored.
Performance (text)

This section summarises the company’s overall performance in the• Benchmark analysis

Benchmark. It covers:• Drivers behind its scores•	Main areas where the company scores well or below average compared to peers
How company was evaluated:

This figure shows the indicators that were applicable to the company.

(by indicator)
Opportunities (text)• Benchmark Methodology Report 2020
• Benchmark analysis

This section outlines opportunities for the company to do more to• Benchmark analysis

address AMR. The opportunities listed take into account company-specific characteristics.
Changes since 2020

This section provides an update on the most notable changes on the• Benchmark analysis

company’s actions to curb AMR since the 2020 Benchmark. It includes•	Public sources, such as company website

a selection of new or expanded commitments, strategies, activities,

or press releases

and programmes. These updates may have taken place after the periodof analysis and are not necessarily scored by the Benchmark.
Sales and Operations (text)

Therapeutic areas: Therapeutic areas the company focuses on, asavailable in public sources.

•	Annual report for the fiscal year ending 31
December 2020 or later (or, equivalently,
forms 10-K or 20-F)

Business segments: How the company is operationally organised, as• Company website

presented in official company sources.

•	Press releases by company or news

Product categories: Types of products the company markets, as avail-• Stock exchange communications

websitesable in public sources, and standardised by the Benchmark across companies.
M&A since 2018: Merger & acquisition activity since 2020 specifically
relevant for antibacterial or antifungal products.
Revenues by product (figure)This figure shows, where possible, a breakdown of the company’s rev-•	Annual reports for the fiscal years 2019

enues in fiscal year 2020 into: antibacterial and antifungal medicines;

and 2020 (or, equivalently, forms 10-K or

antibacterial vaccines; other pharmaceuticals; other (non-pharmaceu-

20-F)

ticals).
If such breakdown is not possible, categories are based on companies’
business segments or may show only the total revenue.
Revenues by region

This figure shows a breakdown of the company’s revenues by geo-

(figure)graphic region in fiscal year 2020.

•	Annual reports for the fiscal years 2019and 2020 (or, equivalently, forms 10-K or
20-F)

The categories are based on official company reports but may be
aggregated. If no breakdown by region is possible, the figure shows
only the total revenue. If this is the case for both the regional and product breakdowns, there is a single figure showing the total revenue.

181

Antimicrobial Resistance Benchmark 2021

Pipeline (text)

This section describes the R&D pipelines of the Large Research Based• Benchmark pipeline analysis

Pharmaceutical companies for pathogens in scope with respect to the•	The WHO innovativeness criteria are listed

following points:

in:­	 • 2020 Antibacterial agents in clinical

Pipeline size: Provides the total number of projects in scope, including

and preclinical development: an over-a breakdown by type.

view and analysis. Geneva: World HealthOrganization; 2021.

Development stages: Provides a count of the company’s projects in­	 • 2019 Antibacterial agents in clinicalclinical stage (listing examples), followed by a count of projects in dis-development: an analysis of the anti-

covery or pre-clinical stage.

bacterial clinical development pipeline. Geneva: World Health Organization;

Novelty: Lists projects that are considered novel by the Benchmark, as
per the WHO innovativeness criteria and PEW charitable trusts (seeSources column).

2019.
­	 • Antibacterial agents in preclinical development: an open access database.
Geneva: World Health Organization;‘Critical’ and/or ‘urgent’ pathogens: Lists projects that target pathogens defined as ‘critical’ by WHO’s list of priority pathogens and/or
characterised as ‘urgent’ threats by the US Centers for Disease Control
and Prevention (CDC).

2019.
•	The Pew Charitable Trusts: Antibiotics
currently in global clinical development –Mar 2021 update•	The Pew Charitable Trusts: Nontraditional

Regulatory approvals: Lists regulatory approvals for projects targeting
priority pathogens between 22 June 2019 and 15 October 2021.

Products for Bacterial Infections in ClinicalDevelopment – Apr 2021 update.

Pipeline for priority pathogens

This figure shows, where possible, a breakdown of the company’s pipe-• Benchmark pipeline analysis.

(figure)line for pathogens in scope, including projects in antibacterial vaccines;•	Company website and clinical trials

antibacterial medicines; antifungal vaccines; and antifungal medicines.
Portfolio (text)

registries.

This section describes a company’s antibacterial and antifungal prod-• Benchmark Portfolio Analysis

uct portfolio, starting with a comparative statement on the number of•	Registered products identified from theproducts (INN-level) in scope, including a breakdown by type.

EMA, FDA, and the company’s website.
• IQVIA MIDAS® 2017 anti-infectives data

The total number of products reflects the INN only and not the differ-• WHO EML, 21st List, 2019ent formulations.

•	WHO and the Norwegian Institute of

The following information is also listed, as applicable:

Public Health, ATC/DDD Index 2021;
https://www.whocc.no/atc_ddd_index/­ • On-patent medicines•	Appendix II of the Benchmark Methodol-­	 • On-patent vaccines

ogy Report 2019 (Products in Scope for­	 • Off-patent/generic medicines

Access Indicators)­	 • AWaRe medicines: Number of medicines in each WHO AWaRegroup for antibacterials (Access, Watch, Reserve)­	 • Anti-TB medicines: Number of anti-tuberculosis medicines
The classification of products as “Anti-TB medicines” follows the 2019
WHO EML.
For products with a square box, alternative products listed on ATC/
DDD Index 2021 are also treated as on EML.
Products on the market (figure)This figure shows, where possible, a breakdown of the company’s mar-

• Company verification

keted products in scope by antibacterial vaccines; antibacterial medi-•	Registered products identified from thecines; and antifungal medicines.

EMA, FDA, and the company’s website• IQVIA MIDAS® 2017 anti-infectives data

The number of products is based on data from public sources, IQVIA
MIDAS®, and data verified by the company. It may not account for thecompany’s entire product portfolio.

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Antimicrobial Resistance Benchmark 2021

Performance by Research Area:

This section summarises company performance for the Research Area

• Benchmark pipeline analysis

of Research & Development, by indicator. The paragraphs describe•	2020 Antibacterial agents in clinical and

A. Research & Development

the company’s performance and highlight (where available) relevant

preclinical development: an overview and(text)

examples of its activities.

analysis. Geneva: World Health Organization; 2021.

In indicator A.2.2, novelty is analysed for clinical-stage medicine•	2019 Antibacterial agents in clinical devel-

projects only and based on criteria defined by the WHO and PEW

opment: an analysis of the antibacte-charitable trusts (see Sources column).

rial clinical development pipeline. Geneva:
World Health Organization; 2019.

In indicator A.2.4, the assessment is based on the number of unique•	Antibacterial agents in preclinical develop-

candidates (i.e., unique INNs) within the projects that target critical orment: an open access database. Geneva:

urgent priorities.

World Health Organization; 2019.
•	The Pew Charitable Trusts: Antibiotics

In indicator A.3, detailed portfolio-wide or project-specific accessand stewardship plans are analysed for late-stage projects only. This
includes projects in clinical Phase II or III, as well as projects awaiting

currently in global clinical development –Mar 2021 update.
•	The Pew Charitable Trusts: Nontraditional

approval or approved during the period of analysis (2019/06/22

Products for Bacterial Infections in Clinicalto 2021/04/30) but not Phase IV or technical lifecycle projects.

Development – Apr 2021 update.

For medicine projects, the Benchmark looks at both access andstewardship plans, whereas for vaccine projects, where overuse or
inappropriate use is not a concern with respect to AMR, only accessplans are considered.
Pipeline targeting pathogens inThis figure shows the company’s pipeline of antibacterial and antifungal •	Projects submitted by the company forscope (figure)medicines and vaccines targeting priority pathogens. Phase IV projects,

scoring and analysis in the Benchmark,technical lifecycle projects are not shown.

including verification/cross- referencewith publicly available pipeline informa-

Where applicable, regulatory approvals (including label extensions) aretion. Approval data is verified using pub-

noted, including the regulatory body/location and date of approval.

lic sources, e.g., clinical trial registries orData omissions due to confidentiality agreements are noted.

press releases by companies.

Although the figure shows the pipeline as of September 2021, the analysis in the R&D Performance by RA text considers the status of projects at the end of the period of analysis, on 30 April 2021.
Performance by Research Area:

This section summarises company performance for the Research Area

• Benchmark analysis

of Responsible Manufacturing, by indicator. The paragraphs describe•	Official public company sources such as

B. Responsible Manufacturing

the company’s performance and highlight (where available) relevant

annual or CSR reports, CDP Water Secu-(text)

examples of its activities.

rity reports, policy documents or company
websites

In indicator B.2, discharge limits published in the AMR Industry Alliancewebsite were also considered in the assessment, despite not qualifying
as disclosure via an official individual company source.

•	FDA inspection classification database(https://www.fda.gov/inspection-classification-database)•	EMA EudraGMP database (http://eudrag-In indicator B.3, three public databases were searched: the FDA inspection classification database, EMA EudraGMP database and WHO noticeof concern database (see Sources column).

mdp.ema.europa.eu/inspections/displayWelcome.do)•	WHO notice of concern database https://extranet.who.int/pqweb/inspection-services/notice-concern

Performance by Research Area:

This section summarises company performance for each Access indica- • Benchmark analysis
tor in the Research Area of Appropriate Access and Stewardship. The• IQVIA MIDAS® 2017 anti-infectives data

C. Appropriate Accessparagraphs describe the company’s performance and highlight (where• Company websites(text)

available) relevant examples of its activities.

• WHO EML, 20th List, 2017
• WHO EML, 21st List, 2019

In indicators C.1.1 and C.2.1, “on-patent products” refers to all on-pat-•	Appendix II of the Benchmark Methodol-ent antibacterial and antifungal medicines and vaccines that the com-ogy Report 2019 (Products in Scope forpany markets.

Access Indicators)

In indicators C.1.2 and C.2.2, “off-patent products” refers to a company-specific set of off-patent antibacterial and antifungal medicines
based on each company’s highest volume sales data globally and in
21 low-income markets, as provided by IQVIA Midas® 2017 database.
Products were first derived from the 2017 WHO EML and divided into
six categories: four based on the 2017 WHO AWaRe classification ofAccess, Watch, Access/Watch and Reserve and two for antifungals andanti-tuberculosis medicines.
Indicator C.3 considers all antibacterial and antifungal medicines andvaccines in scope for this Benchmark.

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Antimicrobial Resistance Benchmark 2021

Performance by Research Area:

This section summarises company performance for each Stewardship• Benchmark analysis

indicator in the Research Area of Appropriate Access and Stewardship.

• Public sources such as company websites

C. Stewardship

The paragraphs describe the company’s performance and highlightor independent 3rd party websites(text)(where available) relevant examples of its activities. Only antibacterial•	Public sources such as the AMR Registerand antifungal medicines are in scope for this Research Area. The geo-

(https://amr.theodi.org/) which is sharing

graphic scope is global.

surveillance data.
•	AMR Industry Alliance website (https://www.amrindustryalliance.org/)

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Antimicrobial Resistance Benchmark 2021

APPE N D IX IX

Figures

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13
13
13
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Figure 1 Antimicrobial Resistance Benchmark – 2021
Figure 1 Antimicrobial Resistance Benchmark – 2021
Figure 2 More R&D projects target pathogens in the highest risk categories defined by WHO and the CDC.
Figure 3 10 companies now require suppliers to limit the level of antibacterials present in manufacturing wastewaters
Figure 4 One third of products assessed are covered by access strategies
Figure 5 Almost all late-stage medicine candidates now have both stewardship and access plans
Figure 6 Companies report discharge levels are under set limits at 13.4% of sites
Figure 7 12 companies now take measures to mitigate the risk of overselling antimicrobials
Figure 8 Benchmark performance, large research-based pharmaceutical companies
Figure 9 GSK performance by research area
Figure 10 Pfizer performance by research area
Figure 11 Johnson & Johnson performance by research area
Figure 12 Benchmark performance, generic medicine manufacturers
Figure 13 Aurobindo performance by research area
Figure 14 Abbott performance by research area
Figure 15 Viatris performance by research area
Figure 16. What is the data set?
Figure 17. Number of products covered by at least one access strategy, broken down by category
Figure 18. 10 pharma companies support local manufacturing projects across 14 low- and middle-income countries
Figure 19. Uptick in companies requiring all suppliers to set discharge limits
Figure 20. Number of manufacturing sites reported as compliant with antibacterial discharge limits
Figure 21. Companies require suppliers to set limits, but many do not assess whether limits are actually achieved
Figure 22. More stewardship & access plans for late-stage projects
Table 1. Access and stewardship plans cover a diverse range of strategies
Figure 23. Eight innovative medicines and six innovative vaccines in clinical development
Figure 24. How large are the companies’ pipelines – and how far along are the projects?
Figure 25. One third of pipeline targets pathogens in highest risk categories
Figure 26. One third of the pipeline comprises vaccines R&D projects
Table 2. 92 medicine and vaccine projects target priority bacteria and fungi
Figure 27. R&D pipeline for priority pathogens has grown from 77 to 92 projects
Figure 28. Most new projects are innovative
Table 3. Potential game-changing antimicrobials in the pipeline
Table 4. Newly-approved products and label extensions for products already on the market
Figure 29. More stewardship and access plans for late-stage projects
Table 5. Access and stewardship plans cover a diverse range of strategies
Figure 30. Which projects are ready for stewardship and access plans?
Figure 31. Majority of manufacturing sites in this analysis are operated by suppliers
Wastewater discharge option 1. Wastewater is directly discharged into the environment
Wastewater discharge option 2. Wastewater is sent to a public wastewater treatment plant, before being discharged into the environment
Table 6. Depth and breadth of environmental risk management strategies
Figure 32. Uptick in companies requiring all suppliers to set discharge limits
Figure 33. How far do discharge limits apply along the supply chain?
Figure 34. Even where limits are set, quantification and compliance lags behind
Figure 35. Most sites are operated by third-party suppliers, and compliance rates here are low
Table 7. Supplier data often not available, but more positive signs at companies’ own sites
Figure 36. Companies ensuring quality management systems across their supply chains
Figure 37. Number of companies which report setting limits at their own directly-operated manufacturing sites
Figure 38. How do the companies’ approaches to environmental risk management differ between antibacterial and antifungal products?
Figure 39. 166 products in scope for this analysis
Figure 40. 102 countries in scope for access metrics in this analysis
Figure 41. The data set for this analysis
Figure 42. Which LMICs have the most products being filed?
Figure 43. Which on-patent medicines are filed most widely?
Figure 44. Which on-patent vaccines are filed most widely?
Figure 45. Which off-patent/generic products are filed most widely?
Figure 46. Registration filings for on-patent medicines, by company
Figure 48. Registration filings for off-patent/generic medicines, by company
Figure 47. Registration filings for on-patent vaccines, by company
Figure 49. Number of products covered by at least one access strategy, broken down by category
Figure 50. Number and type of access strategies being used for on-patent medicines
Figure 51. Number and type of access strategies being used for off-patent/generic medicines
Figure 52. Number and type of access strategies being used for on-patent vaccines
Figure 53. What are companies doing to ensure a continuous supply of antibiotics, antifungals and vaccines?
Figure 54. What steps are pharma companies taking to ensure continuous supply?
Figure 55. Focus on different strategies to mitigate against risk of shortages
Figure 56. 10 pharma companies support local manufacturing projects across 14 LMICs
Figure 57. Countries in Africa where technology transfers are being carried out
Figure 58. How many priority pathogens do the programmes cover?
Figure 59. How engaged are the companies in AMR surveillance?
Figure 60. Countries with at least one surveillance programme
Figure 61. Countries with at least one surveillance programme covering Candida spp.
Figure 62. Countries with at least one surveillance programme covering S. aureus
Table 8. Overview of surveillance programmes, broken down by company and by priority pathogen
Figure 63. Surveillance programmes share data in different ways
Figure 64. Best practice: AMR surveillance data sharing
Figure 65. How far do companies go in decoupling performance incentives from sales volumes?
Table 9. Overview of sales practices, broken down by company and by coverage of products and geographies
Figure 66. Levels of COI mitigation among the educational programmes assessed by the Benchmark
Figure 67. How many companies report that they are involved with HCP education?
Table 10. Which COI mitigation strategies are used in HCP educational programmes?
Figure 68. The number of educational programmes using different COI mitigation strategies
Figure 69. Which types of adaptations do companies use?
Table 11. How do companies help patients understand the risks of AMR?

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Antimicrobial Resistance Benchmark 2021

APPE N D IX X

Definitions
Access plan

to as antibiotic resistance. See also antimicro-

Capacity building[Working definition, used for analysis]bial resistance.

The company forms partnerships with local

An access plan is a plan set up to ensure thatstakeholders to increase capacity (e.g. by train-

public health needs are taken into considera-

Antibiotic medicine

ing of staff or obtaining equipment and othertion during R&D. These plans may be developed[Working definition, used for analysis]

necessary resources) in order to strengthen thein-house or through collaborations and include

Equivalent to Antibacterial medicine. The term

supply chain.

commitments, strategies, concrete provisions“antibiotic” is used inconsistently in the liter-and other agreed-upon measures (typicallyature to denote either a drug that targets any

Clinical-stage drug development

developed in partnership) to enforce accounta-

type of microorganism in the body or, alterna-[Working definition, used for analysis]

bility. Access plans facilitate availability, acces-

tively, a drug that targets bacteria specifically.

Clinical-stage drug development comprises

sibility and affordability for patients in countries

Given the ambiguity, the Benchmark prefera-phases I through III of clinical development.

within the scope of the Benchmark (e.g., regis-

bly avoids use of this term, referring to the more

Products approved (or awaiting approval)

tration commitments, equitable pricing strate-

general category as “antimicrobial” and to thebetween 22 June 2020 (end of the period

gies, sufficient supply commitments, non-exclu-

more specific one as “antibacterial”.

of analysis for the previous edition of thesivity in specified territories, waiving of patent

Benchmark) and 30 April 2021 are also catego-rights, royalty-free provisions and applying for

Antifungal medicine

WHO prequalification).

[Working definition, used for analysis]

rised as late-stage.

Antimicrobial medicine used to treat fungal

Conflict of interest (COI)

Active pharmaceutical ingredient (API)

infections by directly targeting the fungi that[Working definition, used for analysis]

The active pharmaceutical ingredient (API) iscauses the infection (as opposed to targeting

Within the context of pharmaceutical compa-

the active pharmaceutical component of a med-

the symptoms of the infection or toxins pro-nies’ engagement in public health-oriented ini-

icine that carries out its intended effects. Some

duced by the pathogen).

tiatives, a conflict of interest potentially arises

medicines, such as combination therapies, havewhen the commercial interests of the company

multiple active ingredients that target multiple

Antimicrobial medicine

conflict with the primary interest of protecting

disease pathways and/or symptoms. The inac-[Working definition, used for analysis]

and promoting public health.

tive ingredients of a medicine are referred to as

A medicine used to treat an infectious disease by

excipients.

directly targeting the bacteria, fungi, helminths,

Cross-resistanceprotozoa, or viruses that cause the infection (asCross-resistance refers to the resistance devel-

Adaptive R&D

opposed to targeting the symptoms of the infec-

oped to a usually effective antimicrobial medi-[Working definition, used for analysis]tion or toxins produced by the pathogen).

cine through exposure to a similarly acting sub-R&D adaptations to existing medicines and/or

stance. Cross-resistance can occur among

vaccines. This includes new formulations, new

Antimicrobial resistance (AMR)

human antimicrobials and is also observed

fixed-dose combinations of existing chemical or

Antimicrobial resistance is the ability of

between human antimicrobials and products

biological entities, a new target demographic, or

microbes such as bacteria, viruses, fungi andused in animal health or agriculture (e.g., pesti-

the repurposing of an existing product for addi-

parasites (protozoa or helminths) to grow in thecides, herbicides or fungicides).

tional indications.

presence of an antimicrobial substance (e.g., a
medicine) that would normally kill them or limit

Disability-Adjusted Life Year (DALY)AMR surveillance

their growth. Resistance is a consequence ofThe disability-adjusted life year (DALY) is a[Working definition, used for analysis]

evolution via natural or artificial selection.

measure of disease burden that combines dis-

The continuous and systematic collection, anal-

ease-associated mortality and morbidity. It is theysis and interpretation of antimicrobial infection

Antimicrobial stewardshipsum of the number of years of life lost (YLLs)

and resistance-trend data needed for the plan-A systematic and comprehensive process thatand years lived with disability (YLDs). DALYs

ning, implementation, and evaluation of antimi-

aims to ensure that all aspects of prescribing,allow comparison of disease burden across dif-crobial stewardship activities.

(e.g., drug, dose, duration), dispensing, and theferent populations and health conditions acrossuse of antimicrobial medicines are consistenttime. One DALY equals one lost year of healthy

Antibacterial medicine

with the available evidence on how to minimise

life.

[Working definition, used for analysis]

the emergence of antimicrobial resistance.

Antimicrobial medicine used to treat bacterial

Drug productinfections by directly targeting the bacteria that

Appropriate use of antimicrobials

The finished dosage form of a medicine

causes the infection or the disease process (asThe cost-effective use of antimicrobials, whichobtained at the end of the manufacturing pro-opposed to targeting the symptoms of the infec-

maximises clinical therapeutic effect while mini-

cess, (e.g., the tablet, capsule, or solution con-tion). Biocides are not considered antibacterial

mising both drug-related toxicity and the devel-taining the active pharmaceutical ingredient(s),medicines See also Antibiotic medicine.

opment of antimicrobial resistance [WHO Global

generally, but not necessarily, in association with

Strategy for Containment of Antimicrobial

one or more other ingredients). Also referred to

Resistance, 2001].

as a finished drug product, finished product or

Antibacterial resistance
Antimicrobial resistance occurring specifically informulation.

bacteria. This resistance renders the medicines

Broad-spectrum antibacterial

normally used to treat bacterial infections (e.g.,

Broad-spectrum antibacterial medicines are active

Environmental risk management (ERM)

urinary tract infections, pneumonia, bloodstream

against a wide range of bacterial types and may be[Working definition, used for analysis]

infections) ineffective. Sometimes also referred

used to treat a wide range of bacterial infections.

In the context of antibacterial product manufac-

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Antimicrobial Resistance Benchmark 2021

turing, environmental risk management (ERM)tical ingredient. The selection process is coordi-

wide for marketing, normally as a patented prod-seeks to determine and manage environmen-nated by World Health Organization (WHO) via

uct, on the basis of its documented efficacy,tal risks resulting from the production of anti-

its INN Programme. Each INN is a unique namesafety and quality, according to requirements atbacterials, such as the emergence of antibacte-that is globally recognised and is public property.

the time of authorisation. The originator med-

rial resistance, to protect human health and theenvironment.

icine always has a brand name; this name may,
Late-stage drug development

however, vary among countries.

[Working definition, used for analysis]
Falsified medicine

In the context of the pharmaceutical R&D pipe-

Over-the-counter medicine

A medicine which is deliberately and fraudu-

line, medicine and vaccine candidates in Clinical

A medicine that can be purchased without pre-lently mislabelled with respect to identity and/phase II or Clinical phase III are considered toscription from a healthcare professional.

or source. Falsified medicines may contain nobe in late-stage clinical development. Products

active ingredient, the wrong active ingredi-

approved (or awaiting approval) between 22

Period of analysis

ent or the wrong amount of the correct active

June 2020 (end of the period of analysis for the[Working definition, used for analysis]

ingredient.

previous edition of the Benchmark) and 30 April

The 2021 AMR Benchmark report will assess

2021 are also categorised as late-stage by thecompany activities taking place during a period

Benchmark.

of analysis going from 22 June 2020 to 30 April

Generic medicine
A medicine that is created to be the same as a

2021. For the R&D research area, projects needknown marketed brand-name drug (the origina-

Narrow-spectrum antibacterial

to be ongoing, approved or awaiting approval by

tor medicine) in dosage form, strength, route of

Narrow-spectrum antibacterials are antibacte-

the end of the period of analysis.

administration, quality and performance charac-

rial medicines that are active against a selected

teristics, and intended use. See also Originatorgroup of bacterial types. Examples include colis-

Preclinical-stage drug development

medicine.

tin, an antibacterial that selectively targets[Working definition, used for analysis]gram-negative bacteria, and vancomycin, an

Preclinical-stage drug development comprises

Good Manufacturing Practices (GMP)

antibacterial that selectively targets gram-posi-

the discovery and preclinical phases of drug

Good manufacturing practice (GMP) is a system

tive bacteria.

development.

ently produced and controlled according to

Novel drug candidate

Predicted no-effect concentration (PNEC)

appropriate quality standards. Within pharma-[Working definition, used for analysis]

In the context of environmental risk assessment,

ceutical production this serves to minimise risks

A novel candidate meets at least one of thethe predicted no-effect concentration (PNEC)

such as unexpected contamination, incorrectfour criteria defined in WHO’s report “2020is the concentration of a substance in any envi-

labelling or incorrect dose of the active ingre-

Antibacterial agents in clinical and preclinicalronment below which adverse effects will mostdient. GMP covers all aspects of pharmaceuti-

development” (2021): (1) new chemical class; (2)likely not occur. The PNEC can be based on

cal production (e.g., starting materials, prem-new target; (3) new mode of action; (4) absence

acute (short-term) or chronic (long-term) toxic-

ises, equipment, training and personal hygiene ofof cross-resistance. This assessment is applied

ity data and usually takes account of the uncer-

staff) and includes processes that provide docu-

only to candidates in clinical stage and validated

tainty in extrapolating from collected/available

mented proof that correct procedures are con-by WHO and/or external experts.

data to the entire ecosystem.

turing process. GMP guidelines are establishedOff-patent medicine

Priority pathogen

and overseen by regulatory agencies in individual[Working definition, used for analysis][Working definition, used for analysis]countries or regions, as well as the WHO.

A medicine whose granted patent protection has

Priority pathogens are pathogens for which new

expired. Patent protection typically lasts for 20

medicines and vaccines are highly needed. The

years and is specific to each country.

Benchmark identified this set of priority patho-

employed to ensure that products are consist-

sistently followed at each step of the manufac-

Healthcare Professional (HCP)
Any specialised worker in any branch of health-gens based on the WHO priority pathogens list

care that provides preventive, curative or reha-On-patent/patented medicine

as of 15 January 2020 and the CDC’s US Biggest

bilitative services to the community.

[Working definition, used for analysis]

Threats list as of December 2019.

A patented or on-patent medicine is one which
Intellectual capitalhas received exclusivity rights, allowing the

Product Development Partnership (PDP)[Working definition, used for analysis]

patent holder to prevent or stop others from[Working definition, used for analysis]Intellectual capital is the intangible value of amaking, using, selling or importing the medi-

Product Development Partnerships (PDPs) takecompany, covering its employees (human capi-

cine within the country that granted the patent.

the form of centralised non-profit organisationstal), its relationships (relational capital) and the

The Benchmark determines patent status for its

that facilitate financial risk-sharing across theinfrastructure (e.g. hardware, software, data-

products in scope through a process that com-public and private sectors by pooling and sharing

bases, processes, patents) that supports thebines data from selected regulatory authority

resources, both tangible and intangible, for thework of its employees (structural capital). A

websites (e.g. FDA) and participating companies.

development of medicines, vaccines, and othercompany’s intellectual capital gives it a competi-

health tools.

tive advantage. In the context of the Benchmark,One Healththe intellectual capital of a pharmaceutical com-

An approach used to design and implement

Public-private partnershippany may comprise of, for example, molecule

public health programmes, policies, legislation[Working definition, used for analysis]

libraries, patented compounds, processes andand research in which multiple sectors com-

A public-private partnership (PPP) is a partner-

technologies or unpublished data on pharmaco-

municate and work together to achieve better

ship between one or more public organisations

logical characteristics of compounds.

outcomes. The areas for which a One Healthand the private sector for providing a public asset

approach is particularly relevant include foodor service, in which the private party bears sig-

International non-proprietary name (INN)

safety, the control of zoonosis, and combatingnificant risk and management responsibility,

The International non-proprietary name (INN) is

antimicrobial resistance. [WHO, 2017]

and remuneration is linked to performance. The

a common, generic name selected by designatedBenchmark also considers a partnership between

experts for the unambiguous identification of a

Originator medicine

a non-profit organisation and the private sector

pharmaceutical substance or active pharmaceu-

The medicine that was first authorised world-

to be a PPP.

187

Antimicrobial Resistance Benchmark 2021

Pull incentive
Pull incentives, in the form of extended exclusivity periods, higher reimbursement or market
entry rewards, reward companies for bringing
new drugs to the market through lowering theuncertainty for return on investment.
Push incentive
Push incentives, in the form of grants, partnerships or tax credits, are employed to lower thecost of and de-risk research and development of
a new medicine.
Responsible promotional practices[Working definition, used for analysis]
Promotional activities targeting the generalpublic, patients, and healthcare professionals insuch a way that transparency, integrity, accuracy,
clarity and completeness of information can beensured.
Stewardship plan
[Working definition, used for analysis]
A stewardship plan is a plan set up to ensurethat AMR-relevant public health needs are taken
into consideration during R&D. These plans may
be developed in-house or through collaborations and include commitments, strategies, concrete provisions, and other agreed-upon measures (typically developed in partnership) to
enforce accountability. Stewardship plans facilitate the appropriate use of antimicrobial medicines and reduce the emergence of resistance.
Examples include (but are not limited to) appropriate promotional practices and conducting surveillance studies.
Substandard medicine
Also referred to as “out of specification”, theseare market-authorised medicines that fail tomeet either quality standards or specifications,or both. [based on WHO, 2017]
Zero-liquid discharge (ZLD)ZLD is a waste-treatment process in which amanufacturing site does not discharge any water
into the environment as this will be reused andrecycled while solid residue is incinerated or
sent to landfill. [Ranade & Bhandari, 2014].

188

Antimicrobial Resistance Benchmark 2021

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