2 Vaccine development and implementation

Vaccine implementation varies between countries, but,
generally, those with similar levels of income have comparable
immunization systems. One exception is Japan. Japan has
a level of wealth similar to countries in Western Europe,
Australia and the US, but has an immunization program thatis considerably less progressive. Most industrialized countries
strongly value immunization as a cost-effective means toprevent disease and save on treatment costs, and as a means
to preserve economic development. Immunization is also
valued by some industrialized countries as an asset against
bioterrorism.
Like many other complex and capital-intensive industries, thevaccine industry in highly consolidated. The vaccine market
is dominated by a few large vaccine suppliers in industrializedcountries. The costs associated with developing new vaccinesrequire that vaccines be sold on the global market in order
to be able to recoup R&D investments. Furthermore, almost
all countries import at least some vaccines because not all
national suppliers produce every antigen available.
Vaccine research and development has largely been restricted
to the few vaccine-producing countries. More than two thirdsof new vaccines developed in the past 25 years have beendeveloped in the US52.

52 | VACCINE FACT BOOK 2012

2.1 The global vaccine market

The vaccine market represented about 3% of the pharmaceutical market, at about $28 billion in 201053. Five manufacturers (Merck & Co, GlaxoSmithKline, Sanofi Pasteur, Pfizer,
and Novartis) account for the majority of the market (79.4% in2010) (See Figure 39)54.

sales (See Figure 41)57 and the Global Alliance for Vaccines
and Immunization (GAVI Alliance) is expected to expend morethan $1 billion per year on vaccines.
New vaccines under development are projected to add to thegrowth of the current market.

Vaccine Market Share 2010	
  Other, 20.6 %GSK, 23.0 %Sanofi Pasteur
MSD, 4.2 %Merck, 12.0 %Sanofi Pasteur,
17.5%
Pfizer, 12.7 %	  FIGURE 39. THE DOMINANT SUPPLIERS INF THE GLOBAL VACCINE
MARKET 2010

FIGURE 40. PROJECTED GROWTH OF THE VACCINE MARKET BY ADULTAND PEDIATRIC SEGMENTS

The pediatric vaccine market accounted for about 52% of
the total vaccine market in 2009. Sales of influenza vaccines,
including H1N1 vaccine, were approximately $5 billion in
2010, accounting for about 18% of the vaccine market.
Growth in the market is expected to continue at around 10%compound annual growth rate (CAR) over the next five years.
The pediatric market is expected to grow slightly faster than
the adult vaccine market, at 11% versus 8.2% (See Figure40)55. By comparison, the pharmaceutical market grew by 4 –6% in 2010 and is expected to grow at 4 – 7% through 201356.
The growth in the vaccine market is driven by the sales ofrecently developed vaccines and by new vaccine markets.
Several vaccines now generate more than $1 billion in global

FIGURE 41. BRAND NAME VACCINES THAT GENERATED MORE THAN
$1 BILLION IN SALES IN 2010.

Douglas RG, Sadoff J, Samant V. The vaccine industry. pp 37. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
Knol. Global Vaccine market 2010. Top vaccine companies and blockbuster vaccines.
http://knol.google.com/k/krishan-maggon/global-vaccine-market-2010/3fy5eowy8suq3/152#
54
Hiller A. Vaccines continue to bolster pharma market. PharmPro. December 2, 2010.
http://www.pharmpro.com/articles/2010/12/busines-Vaccines-Continue-to-Bolster-Pharma-Market/
55
Hiller A. Vaccines continue to bolster pharma market. PharmPro. December 2, 2010.
http://www.pharmpro.com/articles/2010/12/busines-Vaccines-Continue-to-Bolster-Pharma-Market/
56
Pharmaceutical Drug Manufacturers. Pharmaceutical market trends 2010.
http://www.pharmaceutical-drug-manufacturers.com/articles/pharmaceutical-market-trends-2010.html
57Knol. Global Vaccine market 2010. Top vaccine companies and blockbuster vaccines.
http://knol.google.com/k/krishan-maggon/global-vaccine-market-2010/3fy5eowy8suq3/152#
52
53

VACCINE FACT BOOK 2012 | 53

2.2 Vaccine development

The development process for vaccines is unique. Vaccine
development is highly capital intensive and risky. Given theimportance of safety with biologics, the vaccine industry ishighly regulated. Vaccine development proceeds in an iterative
fashion. Less than one-tenth of vaccine candidates achievelicensure. The high failure rate is due to the unpredictability ofthe biological organisms needed to produce vaccines, and to
the uncertainty of how the human immune system will process
and react to the vaccine antigen. Some vaccine candidates
may produce appropriate levels of immune response, but
induce important adverse reactions. Other vaccine candidates
may be safe, but ineffective at preventing diseases. With thecurrent tendency to combine several antigens into a single
vaccine, the challenges associated with developing safe andeffective vaccines are even greater.

Process development is further divided into bulk manufacturing
and product finishing. Bulk manufacturing involves the cultureof live organisms, followed by separation and purification of
the desired antigen. Finishing involves the formulation witheither adjuvant and / or stabilizer and the filling of vials orsyringes.

Research to discover new vaccine antigens and novel
approaches to immunization usually takes several years, andcosts tens of millions of dollars. Once a discovery is made,several developments must be undertaken to reach thelicensing stage. Those developments include (See Figure 42):

The development of each of these processes is very lengthy,requiring on average 10–15 years. The total development
costs can reach close to $US1 billion (See Figure 43)58.

Clinical development, as described earlier, involves theiterative process of testing a vaccine candidate in a
progressively larger number of human subjects.
Assay development is required because the vaccine candidate
will be novel and will, therefore, require specific tests to
identify it and characterize the product to the satisfaction of
the regulators.

process development, to produce an economically viablevaccine, consistently, in a manner that satisfies regulators;
and,clinical development, to demonstrate the safety and measure
the protective effect of the vaccine in humans;
assay development, to develop the appropriate tests toascertain the purity, potency and stability of the vaccine underdevelopment.

FIGURE 42. DIFFERENT TYPES OF DEVELOPMENT NECESSARY TO REACH THE VACCINE LICENSING STAGE

54 | VACCINE FACT BOOK 2012	  

2 Vaccine development and implementation

Discovery
several years

Phase I Safety≤ 100
subjects< 1 yearPhase II
Safety / Dose
Ranging
severalhundredsubjects
1 - 3 years

Phase III
Large Scale
Safety /Efficacy
thousands ofsubjects
3 - 5 years

LicenseSubmission
Preparation< 1 year

Licensure

FIGURE 43. VACCINE DEVELOPMENT PROCESS OVER A PERIOD OF UP TO 15 YEARS AT A COST OF UP TO$1 BILLION

2.2.1 Clinical development

After being thoroughly tested in an animal model, vaccine
candidates that are found to be safe and induce immunity
can advance to testing in humans. To license a vaccine,
three phases of clinical testing must be completed in healthy
subjects (See Figure 44)59:

Phase III – large-scale safety and efficacy trials involving thousands of subjects
and requiring 3–5 years
to complete.

Phase I – early safety and immunogenicity trials that involve≤100 subjects and can be completed in under one year;
Phase II – safety, dose ranging, and immunogenicity trials
that involve several hundred subjects and that take 1–3 years
to complete ; and,Image 3. Vaccine manufacturing
in an aseptic environment	
  FIGURE 44. THE FOUR PHASES OF CLINICAL DEVELOPMENT OF VACCINES

Bentley W. Research and the University of Maryland. Center for Bioprocess Innovation.
http://www.umresearch.umd.edu/VPRPubfiles/Center%20for%20Bioprocess%20Innovation%201.29.08.pdf
59
Douglas RG, Sadoff J, Samant V. The vaccine industry. pp 37. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
58

VACCINE FACT BOOK 2012 | 55

“Clinical testing
costs hundreds ofmillions of dollars
to complete. In thefirst three phasesof clinical testing
regulators may
require data from90,000 subjects ormore to affirm safety
and efficacy.

These phases proceed in a stepwise fashion. Only vaccine
candidates that are determined to be safe and capable ofinducing an immune response advance to the next phase(See Figure 15 - Section 1.4). Vaccines under development
are compared to a placebo control group to ensure that theirobserved effectiveness and safety are not random.
A regulator may also require further clinical testing after
a vaccine license has been granted. Clinical studies after
licensure are Phase IV post-marketing studies. These typicallyassess safety and or efficacy in very large populations.
Because of their size, these studies may detect very rare
vaccine-associated events that may have gone undetectedin Phase III testing.
Clinical testing costs hundreds of millions of dollars tocomplete. In the first three phases of clinical testing, regulators
may require data from 90,000 subjects or more to affirm safety
and efficacy60. These subjects may be recruited from multiple
trial centers on all continents.
All clinical data collected from clinical testing must be
thoroughly analyzed and submitted to regulators for theirreview.

GlaxoSmithKline. European Medicines Agency maintains position on the continued use of Rotarix™ (rotavirus vaccine). Media Center, May 21, 2010.
http://www.gsk.com/media/pressreleases/2010/2010_pressrelease_10048.htm
60

56 | VACCINE FACT BOOK 2012

2 Vaccine development and implementation

2.3 Vaccine manufacturing

The manufacture of vaccines is achieved from the
propagation of living organisms. Some of these may be
dangerous human pathogens. Therefore, the manufacture of
vaccines is conducted in a highly regulated and controlledenvironment. All vaccine manufacturers are subject tonational and international regulatory control and mustcomply with specifications for Good Manufacturing Practices(GMP). These requirements vary between countries, but thefundamentals are common:

Propagation entails the multiplication (or amplification) of theliving organism used in the vaccine;•ensure that products are safe for use in humans; and,•ensure that the identity, strength, quality and purity of
products consistently meet regulatory specifications.

Formulation involves the mixing of the purified productin solutions to obtain a desired concentration. It may also
include the addition of preservatives to some vaccines, toensure the sterility of the product over a longer period of time,or to prevent cross-contamination during dose extraction
from vials.

Manufacturing is conducted in an aseptic environment andclosely monitored by quality control measures. Vaccines also
require a strict cold chain to maintain their stability. Under
most circumstances vaccines are shipped and stored underrefrigeration.

Isolation entails the separation of the living organism from thecells or growth media used in the propagation step;
Purification removes all materials that may be adhering to
the isolated organisms, or selectively separates the portion of
the living organism to be used in the vaccine;At the end of the manufacturing process, vaccines are
typically filled in vials or syringes and packaged for shipping
to healthcare providers. (See Figure 46).

The actual production processes vary somewhat for different
types of vaccines. Some components of the manufacturing
process are specific to either viral or bacterial vaccine
production. In all cases, biologicals are inherently variable.
Manufacturers must, therefore, carefully characterize andstore the master seed viruses or bacteria used to start eachproduction run. This helps to ensure the consistency of theend product.
In general, the production of vaccines entails four basic steps(See Figure 45):

FIGURE 45. THE FOUR STEPS IN THE PRODUCTION OF VACCINES	  VACCINE FACT BOOK 2012 | 57

	
  
	
  

2	
  

ISOLATION	  SOLUTIONS	
  

1	
  

FORMULATION	
  PROPAGATION	
  

4	
  

3	
  
FILLING	  

PURIFICATION	
  FIGURE 46. PROCESSES INVOLVED AT EACH OF THE FOUR STEPS OF VACCINE MANUFACTURING

VIRAL VACCINES – Because viruses only grow within living
cells, viruses for vaccines are propagated in cells (e.g. inchicken eggs) or in continuous cell lines (e.g. Vero cells). Oncethe virus has been propagated, it must then be isolated fromthe cells and the cell-culture medium. This may be achievedby several techniques including chemical lyses of the cell,
centrifugation and filtration, or homogenization.
The next step, purifying the virus, may likewise involve multiple
techniques of centrifugation, ultra-filtration, chromatography,
or chemical purification. At this stage, viruses may also bechemically inactivated for killed vaccine preparations.
Then the viral preparation is formulated by mixing it with theconstituents that allow each dose to be safely delivered in theright concentration. This is the point where the product may
also be combined with other antigens (e.g. measles–mumpsrubella vaccine). The formulated product is filled in vials orsyringes. Some vaccines are freeze-dried (lyophilized) at thisstage, to prolong their shelf-life.

58 | VACCINE FACT BOOK 2012

BACTERIAL VACCINES – Bacteria do not require living cells
to propagate and are instead grown in bioreactors containing
specific culture media. After propagation, isolation may
be conducted by centrifugation or specific polysaccharide
extraction techniques. Purification is specific to the antigen,but may include chemical precipitation or fractionation, or
ultra-filtration and chromatography steps. At this stage,
carrier proteins may be conjugated to some polysaccharide
vaccines and the conjugate vaccine is then purified by various
filtration or chromatography techniques. The purified products
are then formulated and at this stage may be combinedwith several other antigens. Some polysaccharide vaccines
contain several types of polysaccharide (e.g. pneumococcal
polysaccharide vaccine contains 23 different types ofpolysaccharide), and some bacterial vaccines are combinedwith other bacterial and / or viral antigens (e.g. diphtheriatetanus-pertussis-Haemophilus influenzae type b-Hepatitis B
or DTP-Hib-HepB).

2 Vaccine development and implementation

2.3.1 Cost trends in vaccine development and manufacturing

Vaccine manufacturing has	
  evolved dramatically overthe last half century (SeeImage 4, Image 5, Image
6)61. New techniques forthe manufacture and testing of vaccines have transformed the manufacturing
environment. New vaccines,
like multivalent conjugate
vaccines, are considerably
more complex to manufacImage 4. Vaccine manufacturing in
the 1950s
ture than traditional inactivated whole-cell ones. The
increased sophistication of
the manufacturing process means that the cost of manufacturing has significantly increased in the last few decades.
In addition, the regulatory environment has evolved to a point
where as many as 500 quality control tests may be conductedin the manufacture of a single vaccine62.

Vaccine manufacture ishighly capital intensive.
A manufacturing facility
alone will cost up to €500
million (about ¥52.6 billion at September 2011)63.
As manufacturing costs arelargely fixed, large manufacturers may produce vaccines in massive amounts(e.g. hundreds of millions ofdoses every year) to achieve
economies of scale in production.

	  Image 5. Vaccine manufacturing in
the 1970s

But scaling vaccine production requires a significant
investment in time. Even for relatively simple processes, suchas vaccine packaging, up to two years may be required to
install and validate new packaging machinery. Building a new
manufacturing facility takes on average five years to complete
and validate with regulatory authorities (See Figure 47).

	  Image 6. Vaccine manufacturing in the 2000s

Rutty CJ, Barreto L, Van Exan R, Gilchrist S. Conquering the Crippler, Canada and the Eradication of Polio. Can J Pub Health 2005; 96 (2) : 12-24.
GlaxoSmithKline. Global Vaccines Public Policy Issues. Addressing developing world production – technology transfer. December 2009.
http://www.gsk.com/policies/Technology-Transfer-Vaccines.pdf
63
Pharmaceutical Networking. GlaxoSmithKline – New vaccine manufacturing plant – St-Amand-les-Eaux, France. 2010.
http://www.pharmaceutical-networking.com/glaxosmithkline-new-vaccine-manufacturing-plant-st-amand-les-eaux-france/
61
62

VACCINE FACT BOOK 2012 | 59

FIGURE 47. TYPICAL TIMELINES TO INSTALL AND VALIDATE NEW INDUSTRIAL CAPACITY FOR DECISIONS MADE IN 2011	  2.4 Vaccine registration and approval

Because of their biological nature and that they are largely
administered to healthy individuals, the entire vaccine
development and manufacturing process is regulated. Before
vaccines are licensed, the three successive phases of clinicaldevelopment must be approved by a national regulatory
authority and may only proceed from one phase to the next
upon approval of the national regulator. When a Phase III
trial has been completed, the manufacturer must apply fora license to sell the vaccine. The license application review
is so thorough and complete that it takes between one andtwo years to complete (See Figure 48). The regulator has
the authority to refuse or withdraw a product license if the
manufacturer is not compliant with current regulations.
After vaccines are licensed, manufacturing is strictly controlled
by regulators who test and have authority over the release ofeach production batch of vaccine. Regulators test for:••safety;identity;

60 | VACCINE FACT BOOK 2012•••

purity;potency; and,sterility.

Regulators also monitor the consistency of product from one
production batch to the next (See Figure 49). Inactivation
and attenuation are also checked to ensure that the productdoes not expose to risk. Regulators will subject the productto multiple tests, with redundant checks, to ensure that thetesting itself is yielding correct results.
General safety testing is performed by injection of the finalcontainer product in the abdomen (intraperitoneal) of mice orguinea pigs.
Identity testing is specific to the nature of the vaccine, but
can include neutralization of a live-attenuated viral vaccinewith an antiserum.
Purity testing must demonstrate that the vaccine is free of2 Vaccine development and implementation	  FIGURE 48. REGULATORY PROCESS FOR VACCINES UNDER DEVELOPMENT

Sterility
Testing

FIGURE 49. REGULATORY TESTING OF LICENSED VACCINES

extraneous materials, including moisture and pyrogenic
substances. The products used in the manufacture of thevaccine must also meet standards of purity.
Potency testing involves demonstrating that the vaccine
confers protective immunity. The tests are specific to thevaccines being tested, but often involve virulent challenge inan animal model, or virus titration, or other quantification of anantigen. It is also necessary to demonstrate that the potencyof the individual components of a combination vaccine arepreserved when combined (because some antigens can
reduce the immune response to others).

	
  Sterility is tested on both bulk and finished vaccines.
Regulators require viral seeds and cell substrates used in
vaccine production to be tested to ensure that they do not
introduce contaminants. Cell substrates are well characterized
to ensure that they are as safe as possible.
Regulators also regularly inspect manufacturing facilities
to ensure compliance with current Good Manufacturing
Processes (GMPs). GMPs are a set of guidelines that ensure
consistency in quality of production.

VACCINE FACT BOOK 2012 | 61

Regulators control the labels on final containers andaccompanying product inserts. Labeling and package inserts
must be supported by scientific data and the regulator reviews
the language to ensure that it is not misleading, or false. Anychanges will usually require the regulator’s approval first.
Regulators may also regulate the advertising of products andmonitor advertising for misleading claims. Claims for products
must be balanced with information about their safety.

Prior to licensure, vaccines are regulated by the Investigational
New Drug (IND) Regulations. The vaccine developer (sponsor)
must apply for permission to conduct a clinical study. The
application must include information about:In order to produce safe and efficacious vaccines and tocomply with regulations, vaccine manufacturers carry out
extensive quality assurance and quality testing during the
manufacture of vaccines. Up to 500 quality control tests
may be conducted in the manufacture of a single vaccine64.
Quality testing may account for as much as 70% of the time
to manufacture65.

•

How vaccines are regulated in the US•••

the composition of the investigational new product;
the source of the investigational new product;
the method of manufacture of the investigational new
product; and,the methods used to determine the safety, purity, andpotency of the investigational new product.

The sponsor must also provide a summary of all laboratory
and animal pre-clinical testing. A description of the proposed
clinical trial and the qualifications of the investigators are also
required (See Figure 51). The endpoints for vaccine licensure
include vaccine safety and efficacy, but safety must be
demonstrated at each phase of the study.

The US Biologics Control Act, enacted in 1902, noted that
testing the purity of a final product was insufficient to ensure
quality. It required that manufacturing facilities be inspected.
In 1944, the Public Health Services Act empowered the
US government to license both biologicals and biologicalmanufacturing facilities. It became illegal for biologicals to be
sold without a license.
Vaccines are regulated by the Food and Drug Administration’sCenter for Biologics Evaluation and Research (CBER).
Vaccine developers must apply to CBER for permission toboth develop and sell vaccines (See Figure 50).

FIGURE 50. PERMISSIONS THAT MUST BE SOUGHT FROM THE FDA’S CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER) FOR
THE DEVELOPMENT AND SALES OF VACCINES	
  GlaxoSmithKline. Global Vaccines Public Policy Issues. Addressing developing world production – technology transfer. December 2009.
http://www.gsk.com/policies/Technology-Transfer-Vaccines.pdf
65
Cutliffe N. 2010. Pathway to access: Manufacturing, supply, and procurement systems. In: Building on the legacy of vaccines in Canada: value, opportunities, andchallenges. BIOTECH Canada. http://www.biotech.ca/uploads/vic/vaccines_7_2010.pdf
64

62 | VACCINE FACT BOOK 2012

2 Vaccine development and implementation	  FIGURE 51. REQUIREMENTS FOR AN INVESTIGATIONAL NEW DRUG APPLICATION

When studies are near completion and show promise of safety
and efficacy, the sponsor may submit a Biologics License
Application (BLA) to the CBER Office of Vaccines Researchand Review (OVRR). The application must submit evidenceof compliance with standards for all of the requirements
shown in Table 14. In addition, the application must include
a description of:
•
•
•
•
•
•

the manufacturing process;data on stability;
product samples and lot test results;
samples labels, enclosures and containers;
address of locations of manufacture; and,an environmental assessment.

Evidence of Compliance

Required submissions

Organization and personnel

Manufacturing process

Buildings and facilities

Stability data

Equipment

Lot testing results

Control of components,
containers and closures

Product samples

Production and processcontrols

Sample labels

Packaging and labeling controls

Enclosures and containers

Holding and distribution

Environmental assessment of
manufacture

Laboratory controls
Records to be maintained
TABLE 14. REQUIREMENTS FOR A BIOLOGICS LICENSE APPLICATION(BLA) SUBMISSIONVACCINE FACT BOOK 2012 | 63

The BLA also includes a site inspection. This involves an indepth review of:
•
•
•
•
•
•

facilities;
records;
production processes;
equipment;
quality control methods; and,personnel.

Once a vaccine has been licensed, post-marketing regulation
requires manufacturers to submit test samples and test
results from each production lot. CBER must “release” orreject the lot based on the results submitted and/or its own
testing. Manufacturers are inspected at least every two years(every year for influenza vaccine producers, since there is a
new influenza formulation every year) for:•••process related issue (documentation of processes);quality related issues (reporting of out-of-specs, productrelease, training of personnel); and,facility and production related issues (heating, ventilation,
air conditioning).

See Figure 52.

Committee for Medicinal Products for Human Use (CHMP)
at the European Medicines Agency (EMA), may also regulate
vaccines.
In Europe, manufacturers can license vaccines either througha centralized procedure of the EMA, which allows for a single
market authorization within EU member states, or they canalternatively license through their national regulatory authority.
If they license through their national regulatory agency,
licenses will be limited to the country where the license wasissued.
Regulatory harmonization
Europe, the US and Japan, have sought to increase regulatory
harmonization between countries through the International
Conference on Harmonization (ICH) of drugs. Increasingly,
national regulatory agencies are exchanging information.
The EMA and US FDA, for instance, have confidentiality
agreements that allow for the exchange of information on legal
and regulatory issues, inspection reports, and post-marketingsurveillance. The US FDA also has similar confidentiality
agreements with the NRAs of Australia, Canada, France,
Germany, Israel, Japan, Mexico, New Zealand, Ireland,
Singapore, South Africa, Switzerland and the UK.

How vaccines are regulated in countries other thanthe US
Industrialized countries have similar regulatory agencies
to the US FDA’s CBER. But each country’s requirementsof vaccine manufacturers are slightly different. In addition,
supra-national regulators, such as the European Union’s
Processes

Quality

Facilities andProduction

Documentation ofprocesses

Reporting ofout-of-specs

Heating

Product release

Ventilation

Personnel training

Air-conditioning

FIGURE 52. AREAS INSPECTED BY THE CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER) AT VACCINE MANUFACTURING SITES

64 | VACCINE FACT BOOK 2012

2 Vaccine development and implementation

2.5 Vaccine funding

Routine immunization of children is considered one of themost cost-effective interventions in health. Governments
have a vested interest in immunization because, in addition
to protecting the individual, immunizations also protect
the community from disease. Therefore, all governments
recommend vaccines for public use as a cost-effective means
to reduce the occurrence of diseases and their associatedtreatment or management costs.

How governments select which vaccines to use is alsovariable from country to country. Usually, governments rely on
their National Technical Advisory Groups (NITAGs) to review
the balance of benefits and risks associated with available(or soon to be available) vaccines. Their recommendations
may be periodically reviewed and modified, if epidemiology
changes (e.g., the eradication of smallpox) or safety issues
arise.

Which vaccines a government recommends depend on
several factors. For example:

Many countries are also mandated by their national laws
to fund recommended vaccines, to ensure that the target
population has sufficient access to recommended vaccines.

•••

the epidemiology of a vaccine-preventable disease(i.e., how frequently it occurs, how many people it affects
when it does occur);the severity of a disease (i.e., whether it can be fatal); and,the public’s concern for the disease (e.g. meningitis).

2.5.1 US Advisory Committee on Immunization Practices (ACIP)

The goals of the Advisory Committee on Immunization
Practices (ACIP) are to provide advice that will reduce theincidence of disease and increase safe use of vaccines. The
committee members are appointed by the Secretary of Healthand Human Services (HHS) to provide guidance to HHS andthe CDC on the control of vaccine-preventable diseases. The
committee develops written recommendations on age ofvaccination, number of doses, and contraindications. HHS
and the CDC must endorse ACIP’s recommendations forthem to be enacted.
ACIP’s recommendations are the basis for the annual CDC“childhood and adolescent” and “adult” immunization
schedules. Vaccines recommended for routine administrationin children are covered by the Vaccines for Children program(VFC). The VFC covers children up to 18 years of age whoare eligible for Medicaid, uninsured, Native American, or
underinsured. These vaccines are provided to private sector
providers for vaccination of eligible children (about 45% ofbirth cohort) (See Figure 53). Historically, HHS and the CDC
have endorsed all ACIP recommendations.
In addition, the section 317 Federal Grant Program,appropriated annually by Congress, can be used to ensure
coverage of both children and adults who would otherwise
not have access to ACIP recommended vaccines, through the
public or private sectors.
In the US, most private insurers cover ACIP recommended
vaccines and about 55% of children have insurance coveragefor immunization. Under the Affordable Healthcare Act, healthinsurers must now provide ACIP recommended vaccines at
no out-of-pocket expense to the policyholder, and insurers
cannot charge premiums for vaccines.

VACCINE FACT BOOK 2012 | 65

US Congressappropriates
funds
HHS Endorses
ACIP
Recommendations
ACIP
Recommends
vaccines

FIGURE 53. FUNDING FOR THE VACCINES FOR CHILDREN (VFC) PROGRAM IN THE US“
The goals of theAdvisory Committee
on Immunization
Practices (ACIP) are
to provide advice
that will reduce theincidence of disease
and increase safeuse of vaccines.
66 | VACCINE FACT BOOK 2012

VFC purchases
vaccines for children
up to 18 eligible for
Medicaid, under- or
uninsured, or Native
American2 Vaccine development and implementation

2.5.2 Australia

The decision to adopt a vaccine into the national immunization
schedule includes advice from the Australian TechnicalAdvisory Group on Immunisation (ATAGI) and an economic
assessment of the candidate vaccine by the Pharmaceuticals
Benefits Advisory Committee (PBAC). A decision to adopt
a vaccine incurs an obligation to fund the new vaccine. The
decision is made by the Minister for Health and Ageing, or thegovernment’s cabinet, if funding of more than AUS$10 million
is required (See Figure 54).

adviseThe National Immunisation Committee, in turn, is responsible
for the implementation of the Immunise Australia Program.
The Immunise Australia Program provides vaccines at nocharge through the National Immunisation Program (NIP)
Schedule, which currently includes 16 vaccines66.
Funding is provided by the Australian government througha number of channels, including governments of States andTerritories for the NIP, Medicare (the universal health insurancein Australia), the subsidy of immunization provided throughprivate care, and to the Victorian Cytology Service for theadministration of HPV (See Figure 55).

Australian TechnicalAdvisory Group on
Immunisation (ATAGI)

Pharmaceutical Benefits
Advisory Committee(PBAC)

review submissions fromvaccine companies

implement

adviseconduct economic
assessments

recommend

National Immunisation
Programdecide andfund
Australian Minister for
Health and Ageing or
cabinet of government

FIGURE 54. DECISION-MAKING PROCESS FOR VACCINE FUNDING IN AUSTRALIA

Australian Government. Department of Health and Ageing. Immunise Australia Program. About the Program.
http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/about-the-program
66

VACCINE FACT BOOK 2012 | 67

MedicareState andTerritorial
Governments
for NIP

Victorian
Cytology
Service(HPV)

Australian
Gov’t
Funding

Subsidizationof Private Sector
Delivery

FIGURE 55. CHANNELS OF GOVERNMENT FUNDING FOR IMMUNIZATION IN AUSTRALIA	
  2.5.3 Other

Most industrialized countries have similar advisory groups(see Table 13, section 1.8) and formal funding processes for
immunization. In Europe, the source of funding varies between
countries. In Germany, the costs of immunization are covered
mostly by statutory insurance provided by employers. In other
European countries, such as the UK, the national government
provides for all recommended vaccines to the public at
no cost.
Most countries in the Asia-Pacific region rely on national
expert immunization committees to recommend vaccinesand most countries then provide recommended vaccines at
no cost through public sector health outlets.

68 | VACCINE FACT BOOK 2012

Many developing countries do not have functioning NITAGs
and may rely heavily on the WHO for immunization policy andon donor funding for immunization. A full review of NITAGs
is available in Vaccine at: http://www.sivacinitiative.org/
download/Vaccine_Supplement_NITAGs_19042010.pdf.

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