REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL on a feasibility study of an active-substance-based review system (‘monographs’) and other potential alternatives for the environmental risk assessment of veterinary medicinal products
Date: 2023-01-13
Institutions: Directorate-General for Health and Food Safety, European Commission
Subjects: drug surveillance, environmental impact, environmental protection, environmental risk prevention, market approval, monograph, veterinary medicinal product

EN 

  EN 

   EUROPEAN COMMISSION  Brussels, 13.1.2023  COM(2023) 9 final  REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL on a feasibility study of an active-substance-based review system (‘monographs’) and other potential alternatives for the environmental risk assessment of veterinary medicinal products  
 
 
1. 

INTRODUCTION 

This  report  delivers  on  the  obligation  of  the  Commission  pursuant  to  Article 156  of 
Regulation (EU) 2019/6 of the European Parliament and of the Council1 to present the 
findings  of  a  feasibility  study  on  an  active-substance-based  review  system  and  other 
potential  alternatives  for  the  environmental  risk  assessment  (ERA)  of  veterinary 
medicinal products (VMPs). 

It also outlines the conclusions of the Commission with regard to the potential impacts, 
as  well  as  the  practicability  of  possibly  implementing  a  new  approach  to  ERA  at  the 
current point in time, when the implementation of the new legal framework on VMPs 
has just begun and is still under development. 

2.  BACKGROUND 

Both human healthcare and veterinary care rely on pharmaceuticals. About 3,000 active 
pharmaceutical  ingredients  (APIs)  are  authorised  in  either  human  or  veterinary 
medicines, or in both, with a wide variability across Member States2. At present, some 
600 APIs are authorised in VMPs in the EU. Some of the APIs are used also as active 
substances in biocidal products or plant protection products. 

While  the  benefits  of  the  responsible  use  of  these  substances  in  VMPs  are  widely 
recognised, there is concern over the potential adverse effects of these substances on the 
environment  and  on  human  health  via  the  environment.  The  concern  related  to 
pharmaceuticals  in  the  environment  has  been  addressed  by  the  legislators.  The 
requirement  for  an  ERA  of  VMPs  as  part  of  the  marketing  authorisation  process  was 
first introduced by Directive 92/18/EEC3. Applicants for new marketing authorisations 
(MAs) for VMPs are to provide an ERA, based on two successive phases4. In Phase I, 
the  potential  exposure  of  the  environment  to  the  VMP  in  light  of  the  intended  use  is 
assessed. Phase II5 is only to be performed for VMPs for which the Phase I concludes 
that,  taking  into  account  the  exposure  of  the  environment,  there  is  a  need  for  a  more 
extensive  assessment.  This  phase  is  structured  around  the  risk  quotient  approach  and 
combines the extent of exposure with further data on the fate and effects of VMPs on 
the  environmental  compartments  of  concern.  Currently,  ERA  is  based  on  several 
guidelines:  Veterinary  International  Conference  on  Harmonization  (VICH)  Guidelines 
66 and 387 and the Guideline8 of the Committee for Medicinal Products for Veterinary 

1  Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary 

medicinal products and repealing Directive 2001/82/EC (OJ L 4, 7.1.2019, p. 43) 

2  European  Commission,  Directorate-General  for  Environment,  Kümmerer,  K.,  Options  for  a  strategic 
report,  Publications  Office,  2019, 

to  pharmaceuticals 

the  environment: 

final 

in 

approach 
https://op.europa.eu/s/wEcR 

3  Commission Directive 92/18/EEC of 20 March 1992 modifying the Annex to Council Directive 81/852/EEC 
on the approximation of the laws of Member States relating to analytical, pharmacotoxicological and clinical 
standards and protocols in respect of the testing of veterinary medicinal products (OJ L 97, 10.4.1992, p. 1) 
Ibid., Section 5.3 of the Annex. 
Ibid., Section 5.4 of the Annex. 

4 
5 
6  Committee  for  Medicinal  Products  for  Veterinary  Use  (CVMP),  Guideline  on  Environmental  Impact 
Assessment (EIAs) for Veterinary Medicinal Products – Phase 1 (CVMP/VICH/592/98-FINAL), available at: 
https://europa.eu/!ytmMgd 

EN 

1 

EN 

 
                                                           
Use (CVMP). Under Directive 2001/82/EC9, all generic VMPs had to undergo an ERA 
regardless  of  whether  such  information  was  already  available  for  the  originator  VMP. 
This requirement provided environmental information on a number of legacy products 
and helped improve environmental protection. 

Similarly to the previous legislation10, Regulation (EU) 2019/6 requires an ERA for new 
marketing  authorisation  (MA)  applications  according 
the  above-mentioned 
principles. However, with its entry into application on 28 January 2022, an ERA is no 
longer  required  for  generic  applications,  except  for  generics  for  which  the  reference 
VMP  was  granted  a  MA  before  1  October  200511.  Another  important  change  is  the 
possibility  for  the  competent  authorities  (CAs),  when  harmonising  summaries  of 
product characteristics and in accordance with Article 72 of Regulation (EU) 2019/6, to 
request the marketing authorisation holder (MAH) to update the relevant environmental 
safety documentation of reference VMPs that were authorised before October 2005 and 
identified as potentially harmful to the environment12. 

to 

The  current  product-based  ERA  system  has  a  number  of  drawbacks:  it  does  not 
guarantee a consistent and harmonised evaluation of the environmental risks of VMPs 
containing the same active substance; there is no legal obligation to review existing risk 
assessments to take into account scientific developments; there is a lack of transparency 
since the data are not publicly available; and VMPs authorised before October 2005 are 
not automatically revised by the competent authorities and thus do not have an ERA in 
line with the current guidelines. 

In autumn 2020, the Commission appointed a contractor to conduct a feasibility study to 
identify,  collect  and  analyse  evidence  of  the  appropriateness  and  practicability  of 
moving towards an active-substance-based system instead of the current product-based 
one. 

In  its  report13,  the  contractor  examined  the  possible  impacts  of  an  active-substance-
based ‘monograph system’ along with two alternative proposals from the industry and 
assessed the efficiency and effectiveness of these proposals in achieving the objectives 
of  Regulation  (EU)  2019/6.  For  the  conduct  of  the  feasibility  study,  the  contractor 
performed  a  literature  search  and  exploratory  interviews  with  stakeholders.  Based  on 
these,  the  contractor  identified  the  sources  of  relevant  evidence  and  remaining  data 

7  Committee  for  Medicinal  Products  for  Veterinary  Use  (CVMP),  Guidelines  on  Environmental  Impact 
Assessment  for  Veterinary  Medicinal  Products  Phase  II  (CVMP/VICH/790/03-FINAL),  available  at 
https://europa.eu/!bRyWpH 

8  Committee  for  Medicinal  Products  for  Veterinary  Use  (CVMP),  Guideline  on  environmental  impact 
assessment  for  veterinary  medicinal  products  in  support  of  the  VICH  guidelines  GL6  and  GL38 
(EMA/CVMP/ERA/418282/2005-Rev.1), available at: https://europa.eu/!fQjmTC 

9  Directive  2001/82/EC  of  the  European  Parliament  and  of  the  Council  of  6  November  2001  on  the 

Community code relating to veterinary medicinal products (OJ L 311, 28.11.2001, p. 1) 

10  Ibid. 
11  Regulation (EU) 2019/6, Article 18(7). 
12  Ibid., Article 72. 
13  Schwonbeck, S., Breuer, F., Hahn, S., Brinkmann, C., Vosen, A., Radic, M., Vidaurre, R, Alt, J., Oelkers, K., 
Mezler, A., Floeter, C.,  Feasibility Study of an Active-substance-based Review System (‘Monographs’) and 
Other Potential Alternatives for the Environmental Risk Assessment of Veterinary Medicinal Products, EW-
06-21-127-EN-N,  European  Union,  Luxembourg,  2021,  ISBN  978-92-76-42335-5,  doi:  10.2875/94477, 
available at https://op.europa.eu/s/wvC9 

EN 

2 

EN 

 
                                                                                                                                                                                     
gaps.  In  a  second  step  the  contractor  attempted  to  fill  in  some  of  these  data  gaps  by 
means of structured interviews and an online survey. 

3.  OVERVIEW OF THE MONOGRAPH SYSTEM AND THE ALTERNATIVES EVALUATED 

Monograph system 

The  active-substance-based  monograph  system,  proposed  by  Rönnefahrt  et  al.14, 
provides  for the set-up of an EU-wide uniform collection of relevant  and high-quality 
environmental data for APIs used in VMPs on the EU market. The monographs would 
be mandatory for the APIs of VMPs that require an ERA with a Phase II assessment and 
antiparasitic  VMPs  for  food-producing  animals,  as  these  are  expected  to  lead  to  a 
greater exposure and negative impact on the environment. 

The monograph system would contain information only on the APIs used in VMPs and 
not on specific VMPs. It would thus not constitute an approval system nor replace the 
ERA for a VMP, but rather deliver data to be used in the subsequent ecotoxicological 
evaluations at product level. The monograph for an API would thus contain the relevant 
environmental information,  which is  essential for the further development  of the ERA 
for  a  VMP  containing  that  API.  In  the  current  system  each  MAH  needs  to  perform 
research  to  obtain  these  API  data  to  prepare  the  ERA  for  the  VMP.  The  monograph 
system would thus facilitate the development of product-based ERAs on the basis of the 
API  data.  Moreover,  making  the  API  environmental  data  publicly  available  would 
increase transparency and enhance the level-playing field for MAHs. 

The  minimum  data  in  the  monograph  would  be  study  summaries,  endpoints  of 
ecotoxicological studies, endpoints regarding physicochemical properties, and endpoints 

p. 

Agency, 

Brussels, 

Belgium. 

Germany: 

14  Rönnefahrt, I., Experiences with environmental risk assessment in the authorization procedure of Veterinary 
Medicinal  Products,  in  International  Workshop  on  Eco-Pharmacovigilance  of  Veterinary  Medicinal 
Products.  2013,  Federal  Environment  Agency,  Dessau-Roßlau:  4.-5.  December  2013,  Berlin.  p.  1-27, 
available 
at: 
https://www.umweltbundesamt.de/sites/default/files/medien/378/dokumente/roennefahrt_vortrag_veroeffentl
ichung_2.pdf , accessed on: 9 September 2022; 
Rönnefahrt,  I.,  Monograph  system  of  active  pharmaceutical  substances:  necessity,  challenges  and 
perspectives,  in  Workshop  „Monograph  system  on  active  pharmaceutical  substances“.  2014,  Federal 
Environment 
at: 
https://www.ecologic.eu/sites/default/files/event/2015/4_monograph_system_workshop_2014_roennefahrt.p
df, accessed on: 9 September 2022 
Rönnefahrt, I., N. Adler, and S. Hickmann. Paradigm shift - Towards a substance-based environmental risk 
assessment  of  pharmaceuticals.  in  SETAC  Europe  Annual  Meeting  2016.  Nantes,  France:  Federal 
Environment 
at: 
https://cdn.ymaws.com/www.setac.org/resource/resmgr/abstract_books/setac_europe_abstractbook_na.pdf, p. 
305, accessed on: 9 September 2022 
Rönnefahrt,  I.  and  N.  Adler,  Harmonised  environmental  information  of  pharmaceutical  substances  –  the 
essential base for risk assessment and risk management  in International Conference on Risk Assessment of 
Pharmaceuticals in the Environment (ICRAPHE). 2016, Federal Environment Agency: 8–9 September 2016, 
at: 
Paris, 
https://www.acadpharm.org/dos_public/ICRAPHE_abstract_book_VF.pdf, p. 129, accessed on 9 September 
2022 
Rönnefahrt,  I.,  The ERA master file concept, in  Workshop „How to achieve an appropriate Environmental 
Risk  Assessment  of  Veterinary  Medicinal  Products”.  2017,  Federal  Environment  Agency,  Germany: 
Brussels, 
at: 
https://www.umweltbundesamt.de/sites/default/files/medien/362/dokumente/05_era_master_file_system_ron
nefahrt.pdf, accessed on: 9 September 2022. 

Belgium, 

available 

available 

available 

available 

Agency, 

abstract 

abstract 

France. 

1-17, 

1-14, 

1., 

p. 

p. 

EN 

3 

EN 

 
                                                           
fate 

the  highest  Predicted 
(degradation  and  adsorption), 
on  environmental 
Environmental  Concentration 
the  highest  Environmental 
in  soil  (PECSOIL)  or 
Introduction  Concentration  in  water  (EICaquatic)  resulting  from  the  existing  Phase II 
ERAs for any VMPs containing the same API and authorised in the EU. 

The monograph system would first focus on APIs authorised before October 2005 with 
priority  on  those  of  environmental  relevance.  It  would  be  up  to  the  Commission  to 
develop a list of prioritised APIs. 

For  VMPs  already  authorised  in  the  EU  for  which  the  environmental  risk  has  been 
assessed  in  a  Phase II  ERA,  the  necessary  data  would  be  collected  by  all  MAHs 
concerned. In the case of VMPs authorised prior to October 2005 for which an ERA is 
missing, all MAHs of VMPs with the same API would be legally obliged to collaborate 
in a consortium to deliver the environmental data required for the monograph.  

In case of a new reference VMP containing a new API, the company applying for the 
MA  would  deliver  the  necessary  environmental  data  according  to  the  intended  use  of 
the  substance  in  the  new  reference  VMP.  The  scope  of  data  in  the  monograph  would 
depend  on  the  use  of  the  API  in  the  VMP  (e.g.  a  VMP  for  food-producing  animals 
would in most cases require a Phase II ERA). 

The  draft  monographs  would  then  be  assessed  by  EMA.  All  monographs  would  be 
stored in a database, e.g. hosted by EMA. Its content would be publicly available to all 
stakeholders, i.e. academia, environmental authorities, water managers, industry, etc. 

However, the monograph system as proposed by Rönnefahrt et al. does not specify how 
the priority for existing substances would be set by the Commission, how data would be 
added if further VMPs with ERAs are authorised, the responsibilities of regulators and 
the industry, the procedural steps and timelines, costs compensations, which data would 
be included in the monograph and in what format, the approach to monograph updates, 
any  potential  fee  structure,  the  database  requirements  and  other  practical  aspects, 
leaving  these  aspects  for  a  possible  future  legislative  proposal  amending  or 
supplementing Regulation (EU) 2019/6. The contractor attempted to elucidate some of 
these aspects in their MONO4ERA proposal15 which they assessed in parallel with the 
Rönnefahrt et al. proposal. 

Proposal by AnimalhealthEurope 

AnimalhealthEurope’s (AhE) proposal is based on the legal obligation16 for all EU CAs 
to publish a (European) Public Assessment Report ((E)PAR)17 for each authorised VMP 

15  Schwonbeck, S., Breuer, F., Hahn, S., Brinkmann, C., Vosen, A., Radic, M., Vidaurre, R, Alt, J., Oelkers, K., 
Mezler, A., Floeter, C.,  Feasibility Study of an Active-substance-based Review System (‘Monographs’) and 
Other  Potential  Alternatives  for  the  Environmental  Risk  Assessment  of  Veterinary  Medicinal  Products,  p. 
348,  EW-06-21-127-EN-N,  European  Union,  Luxembourg,  2021,  ISBN  978-92-76-42335-5,  doi: 
10.2875/94477, available at https://op.europa.eu/s/wvC9 

16  Regulation  (EU)  2019/6,  Articles 44(10),  47(3),  49(11)  and  52(11)  read 

in  combination  with 

Article 55(2)(a)(v). 

EN 

4 

EN 

 
                                                           
and is focused mainly on making the environmental data public. The existing (E)PARs 
would  however  need  to  be  revised  in  order  to  include  the  results  of  environmental 
studies  in  a  standard,  harmonised  format.  The  body  responsible  for  the  preparation  of 
the  revised  (E)PAR  would  thus  be  the  CAs  in  contrast  to  the  monograph  system 
proposal where most of the work would be done by the MAHs. 

The system would cover new VMPs, already authorised VMPs with ERA but with no 
information in the (E)PAR, as well as VMPs authorised prior to 2005 and without ERA 
in the following way: 

 

For already authorised VMPs, the CAs should use the substantial datasets already 
available  to  them  to  revise  the  existing  (E)PARs  to  include  the  available 
environmental  study  results  for  products  with  a  Phase II  ERA,  where  this  is  not 
already the case. 

For VMPs authorised prior to October 2005 and lacking an ERA, the proposal is limited 
to  the  cases  where  a  summary  of  product  characteristics  (SPC)  harmonisation  is 
initiated. A product can be proposed for SPC harmonisation by the CAs or by the MAH. 
However, it is up to the coordination group (CMDv18) to establish the priorities for this 
SPC  harmonisation.  For  the  update/drafting  of  environmental  information  in  the 
(E)PAR, the CAs are to take into account all information available from both reference 
and  generic  VMPs  and  if  necessary,  request  the  MAHs  to  provide  the  required 
information to update the (E)PAR based on Article 72 of Regulation (EU) 2019/6. 

The (E)PAR  would contain information  on the VMP  itself, environmental data on the 
API and  a summary of the ERA in  a standard, harmonised format. The AhE proposal 
contains  a  tentative  data  table  that  could  serve  as  a  basis  for  the  development  of  a 
harmonised format. But cooperation between CAs, and possibly the industry, would be 
needed to agree upon a standard, harmonised format. The (E)PARs would be centralised 
in  the  Union  Product  Database  (UPD)  referred  to  in  Article 55  of  Regulation  (EU) 
2019/6  and  made  available  to  the  public  in  accordance  with  Article 56(3)  of  that 
Regulation. 

In  the  AhE  proposal,  the  ERA  remains  linked  to  the  VMP  and  its  patterns  of  use, 
whereas the monograph system is limited to the hazards posed by the API. 

However, the AhE proposal lacks clarity on the timeline for the revision of the existing 
(E)PARs; how this could be imposed on the CAs; how a harmonised approach ensuring 
coherent,  consistent  and  complete  environmental  information  in  all  (E)PARs  could  be 
established  and  how  the  work  would  be  prioritised.  In  the  absence  of  a  legally 
enforceable timeline, the completeness of the system would depend on the willingness 
and ability of the individual CAs to provide the necessary resources for the revision of a 

17  The public assessment report in the case of marketing authorisation procedures other than the centralised one 
and the European public assessment report in the case of the centralised procedure  is a document or set of 
documents describing the scientific evaluation and reflecting the conclusion reached by the regulators at the 
end of the evaluation process. It provides a summary of the grounds for approval (or refusal) of the marketing 
authorisation  for  the  specific  veterinary  medicinal  product.  It  is  made  available  to  the  public,  after  the 
deletion of commercially confidential information. 

18  Coordination  group  for  mutual  recognition  and  decentralised  procedures  veterinary  medicinal  products 

established under Article 142(1) of Regulation (EU) 2019/6. 

EN 

5 

EN 

 
                                                                                                                                                                                     
high number of (E)PARs. Without a clear legal framework, implementation of the AhE 
proposal  would  also  depend  on  the  CAs  agreeing  to  the  revision  of  guidelines  on  the 
(E)PAR to have a harmonised data presentation. 

Proposal by Access VetMed 

Access VetMed (previously named European Group for Generic Veterinary Products – 
EGGVP)  also  proposed  an  alternative  system.  Its  scope  is  limited  to  reference  and 
generic  VMPs  authorised  before  October  2005.  The  proposal  considers  that  VMPs 
authorised after October 2005 have sufficient ERA data available. For reference VMPs 
authorised  before  October  2005,  the  CA  would  conduct  a  risk-based  review  of  the 
respective VMP in order to categorise its environmental risk, e.g. as ‘high’, ‘medium’, 
‘low’, or ‘very low’, based on the data and ‘know-how’ currently available. 

This  categorisation system  would trigger the need and indicate the priority  to  perform 
an ERA scientific review consisting of the following steps: identification of all existing 
MAs using the UPD, collecting all available ecotoxicological data, complementing with 
data  from  other  sources,  conducting  a  scientific  review  of  the  data  and  proposing  and 
publishing a final set of endpoints and other specific ERA data. 

In  the  event  of  a  reference  VMP  authorised  before  October  2005,  identified  as 
potentially  harmful  to  the  environment  and  with  no  corresponding  generic  VMP 
authorised  after  October  2005  (which  would  thus  have  the  necessary  ERA  data),  the 
MAH would be responsible for the generation or update of the ERA data. 

Like in  the AhE proposal,  the body  responsible for the above steps would be the CA, 
but MAHs would provide ERA data, if required. 

The main difference with the AhE proposal  is  that  in  this proposal  CAs would not  be 
required  to  revise the (E)PARs for VMPs authorised after October 2005 and the ERA 
data of these products might thus not be publicly available. 

Like the AhE proposal, the Access VetMed proposal lacks clarity on the timeline for the 
risk-based  review  of  the  VMPs  authorised  before  October  2005;  how  this  could  be 
imposed  on  the  CAs;  how  a  harmonised  approach  ensuring  coherent,  consistent  and 
complete  environmental  information  in  all  (E)PARs  could  be  established  and  how  to 
ensure that there would be no difference in approach among CAs to the environmental 
risk categorisation of the APIs. 

4.  ANALYSIS OF THE ADVANTAGES AND DISADVANTAGES OF THE MONOGRAPH SYSTEM 

AND THE ALTERNATIVE PROPOSALS 

4.1. Advantages 

Higher quality of ERA data 

Due to the review and compilation of the ERA data, the data in the monograph system 
would be more robust and of higher quality. For some VMPs authorised before October 
2005,  new  ERA  data  would  need  to  be  generated  according  to  current  guidelines.  By 

EN 

6 

EN 

 
pooling resources, the efficiency in the generation of such new data would be improved, 
e.g. when conducting cost-intensive studies with radiolabelled APIs. 

In comparison, the two alternative proposals, being based on product specific data and 
not  on  substance-based  data,  would  not  solve  issues  such  as  inconsistent  assessments, 
limited  availability  of  environmental  information  and  would  thus  have  a  limited 
contribution to the improvement of the quality of ERA data. 

Enhanced access to ERA data 

With the current  system, environmental authorities and experts such  as researchers do 
not  have  sufficient  access  to  ERA  data.  With  a  monograph  system  and  its 
implementation  in  a  database,  the  requirements  of  the  Aarhus  Convention19  regarding 
public  access  to  environmental  information  and  increased  transparency  for  all 
stakeholder groups would be met. 

The  two  alternative  proposals  remain  focussed  on  product  evaluation.  Therefore,  they 
would  not  solve  the  current  issue  of  identifying  harmful  active  substances  and  the 
access to ERA data would remain limited since these data would need to be searched in 
the  EPARs  of  individual  VMPs.  Moreover,  the  Access VetMed  proposal  is  limited  to 
reference  VMPs  authorised  before  October  2005  and  would  thus  result  in  a  less 
complete database than the two other proposals. 

Enhancement of the level playing field for MAHs 

Equal  treatment  of  ERA  and  Risk  Mitigation  Measures  (RMM)  across  all  MAHs  of 
products containing the same API and using the same route of administration would be 
improved  with  the  monograph  system.  Moreover,  an  active-substance-based  system 
would  be  a  prerequisite  for  the  same  substances  to  be  assessed  consistently  ensuring 
higher environmental protection. 

The  two  alternative  proposals  are  centred  on  product  evaluations  and  would  therefore 
not contribute to the enhancement of a level playing field as each MAH would need to 
generate its own data and this could lead to different conclusions for individual products 
with the same API. 

Guaranteeing the highest level of protection of public and animal health and of the 
environment 

The monograph system would encompass valuable information regarding AMR such as 
effects  on  the  microbial  community,  effects  on  cyanobacteria,  physicochemical 
properties  and  estimates  of  the  concentrations  of  the  substance  released  to  the 
environmental compartments. This would support the One Health approach. 

The  monograph  system  would  also  include  the  assessment  of  whether  substances  are 
persistent,  bioaccumulative  and  toxic  (PBT)  and  thus  increase  the  availability  of  data 

19  Convention  on  Access  to  Information,  Public  Participation  in  Decision-Making  and  Access  to  Justice  in 
447, 

Nations, 

Series, 

Treaty 

2161, 

vol. 

p. 

Environmental  Matters, 
https://unece.org/DAM/env/pp/documents/cep43e.pdf 

United 

EN 

7 

EN 

 
                                                           
important for assessing biomagnification in the food-chain and further residue analyses 
to protect human and animal health. 

Furthermore, the monograph system would contribute to the development of RMMs to 
reduce the pollution of surface water, groundwater and drinking water supply. 

By avoiding test  duplication, the monograph system  would also  reduce the number of 
test animals used, e.g. in ecotoxicology testing. 

The  two  alternative  proposals,  remaining  centred  on  individual  product  evaluations, 
would provide limited benefits as they would not harmonise the environmental data in 
the  ERAs  of  different  products.  They  would  only  harmonise  the  way  in  which  the 
environmental data are presented in these ERAs. 

4.2. Disadvantages 

Administrative burden and cost for CAs 

After  an  initial  phase  of  system  setup,  the  monograph  system  is  expected  to  reduce 
administrative  burden  by  minimising  redundancies  in  the  process  of  generating  and 
providing product-based ERA for the same API. 

Compared to the current system, the monograph system would involve additional costs 
and  administrative  tasks  for  the  CAs,  the  veterinary  pharmaceutical  industry,  the 
Commission  and  EMA.  According  to  the  estimations  made  by  the  contractor,  the 
administrative  burden  for  CAs  for  establishing  and  approving  a  monograph  would 
approximate  to  EUR 4,355/application,  and  the  monetised  burden  for  the  CAs  for 
assessing the ERA on an existing monograph is estimated to be EUR 2,497/application. 
A  full  process  in  the  monograph  system  would  thus  total  approximately  EUR 6,852 
(EUR 4,355 for establishing the monograph + EUR 2,497 for assessing the ERA for a 
VMP), adding an additional cost of approximately EUR 3,027 for the assessment of the 
initial ERA for an API against the approximately EUR 3,825 under the current system. 
Since the cost for establishing the monograph is a one-off, the cost for subsequent ERAs 
for VMPs containing the same API would be lower than in the current system. Starting 
with  the  fourth  marketing  authorisation  process  involving  the  same  API,  the 
administrative  burden  of  the  monograph  system  would  be  lower  than  in  the  current 
system. However, given that according to Article 18 of Regulation (EU) 2019/6 generic 
applications  no  longer  require  an  ERA  (except  in  exceptional  circumstances),  it  is 
unlikely that this situation of four ERAs for the same API would ever occur. 

It  should  be  noted  that  a  monograph  system  would  cause  a  partial  shift  of  the 
administrative burden from the national to the EU level (EMA), because the monograph 
system and associated study assessment are to be centralised at EU level. 

The total costs of the monograph database in the first year were estimated to be around 
EUR 66,800  for  an  external  database  (developed,  maintained  and  stored  by  a  third 
party),  and  EUR 67,200  for  an  internal  one  (developed,  maintained  and  stored  by 
EMA).  Annual  costs  in  the  following  years  have  been  estimated  to  amount 
approximately  to  EUR 7,200  and  EUR 5,900  for  an  external  and  internal  database, 
respectively. 

EN 

8 

EN 

 
It should be noted however that the feasibility study report warns that there is a number 
of  uncertainties  and  assumptions  associated  with  the  cost-estimation.  The  limited 
information available did not allow a precise assessment, nor an estimate of the overall 
impacts  in  order  to  objectively  determine  the  associated  costs.  In  interviews  with  the 
contractor  and  in  the  online  survey,  CAs  expressed  their  difficulties  in  estimating  the 
person hours needed for a not  yet established system. The cost calculation thus seems 
very  low  and  does  not  take  into  account  the  cost  for  reviewing  the  existing  risk 
assessments  in  view  of  scientific  progress.  The  study  recommended  gathering  more 
facts and figures in order to close the remaining knowledge gaps. 

Moreover, the cost-estimation was criticised by AhE and AccessVetMet. According to 
the  industry,  the  costs  are  largely  under-estimated  and  based  on  inaccurate  and 
unrealistic assumptions. 

No  cost  estimation  was  made  by  the  contractor  for  the  two  alternative  proposals. 
Therefore,  no  complete  cost  comparison  can  be  made  between  the  three proposals 
making  it  impossible  to  conclude  on  their  individual  impacts.  However,  taking  into 
account  that  both  alternative  proposals  put  more  responsibility  upon  the  CAs  for  the 
preparation  of  the  revised  (E)PARs,  these  proposals  will  be  more  cost-  and  resource-
intensive for the CAs, while triggering lower costs for industry. 

As the monograph system is expected to increase the burden on the industry (especially 
on  the  innovative  industry)  while  the  two  other  systems  are  expected  to  increase  the 
burden  on  the  CAs,  all  three  proposals  conflict  with  the  objective  of  the  Regulation 
(EU) 2019/6 to reduce administrative burden. 

Impact on availability and functioning of the internal market 

The industry (14 out of 15 respondents, overwhelmingly from the generic industry) and 
some  CAs  (3  out  of  15 respondents)  expect  a  monograph  system  to  have  a  negative 
impact on the availability of VMPs. This could be especially relevant for niche markets 
or  in  smaller  EU  Member  States  with  already  small  numbers  of  VMPs  authorised. 
Products  without  ERA  data  could  be  withdrawn  from  the  market  should  the  costs  of 
monograph establishment occur. In fact, some of the active substances which currently 
do not have an ERA are included in VMPs intended for limited markets, generating low 
profits  for  MAHs  (e.g.  VMPs  for  minor  species  such  as  rabbits,  bees,  aquaculture 
species and goats or for infrequent diseases). An option to mitigate this issue could be to 
provide for the possibility of exemptions from the monograph requirement for MAHs of 
products  for  limited  markets.  However,  this  would  likely  have  an  impact  on  the 
completeness  of  the  system  and  increase  costs  for  the  MAHs  of  the  other  products. 
Moreover, this would not solve the issue for MAs in smaller MS, where VMPs might be 
withdrawn  if  the  applicant  is  forced  to  contribute  to  a  consortium  for  establishing  a 
monograph. 

For innovator companies, the monograph system would likely generate additional costs 
due  to  the  fees  for  assessment  and  maintenance  of  the  monographs,  administrative 
burden,  consortium  costs  and  data  management  costs.  This  would  lead  to  a  further 
decrease  in  attractiveness  of  the  EU  region  regarding  market  entry  for  products  with 
new  APIs,  amplifying  the  trend  towards  fewer  authorisations  of  VMPs  based  on  new 
APIs. 

EN 

9 

EN 

 
Since the alternative proposals (AhE and Access VetMed) require less additional costs 
and administrative burden for MAHs than the monograph system, but rather additional 
costs and burden for the CAs, both are expected to have less impact on the availability 
of VMPs than the monograph system. In light of the additional burden for the CAs, the 
alternative proposals might however create delays in the assessment at the level of the 
CAs or the need for CAs to increase their fees. 

Uncertainty on fees and data access/protection 

Clear  and  proportionate  rules  for  access  to  monographs  would  need  to  be  legally 
defined to ensure that the market is not distorted. Respondents expressed their concerns 
that  if  only  a  few  major  players  controlled  fees  for  access  to  data  as  part  of  the 
collaborative  effort  required  by  the  monograph  system,  the  costs  could  become 
unsustainable for SMEs. 

In general, there were concerns about how SMEs would adapt to the monograph system 
and  if  they  would  be  able  to  benefit  from  collaborative  efforts.  Limited  protection  of 
intellectual property rights due to requirements for cooperation was also mentioned as a 
disadvantage. 

The two alternative proposals do not have the same drawbacks with regards to rules for 
access and potential fees linked to this access. 

5.  ADDITIONAL CONSIDERATIONS 

Impact on the veterinary vs. the human pharmaceutical industry 

The  production  and  use  of  human  medicinal  products  also  have  an  impact  on  the 
environment. Taking into account the relative size of the VMP market (only about 3% 
of  the  market  size  for  human  medicinal  products),  the  additional  effort  that  the 
monograph  system  would  place  on  the  veterinary  pharmaceutical  industry  could  be 
considered  as  excessive  compared  to  the  human  pharmaceutical  industry  and  may  not 
alone be sufficient to ensure a higher level of environmental protection. 

As  explained  above,  the  two  alternative  proposals  are  expected  to  place  less 
administrative  burden  upon  the  pharmaceutical  industry  than  the  monograph  system. 
However, these proposals would be expected to put additional costs and burdens on the 
CAs for VMPs, which could lead to an increase in the fees imposed by these CAs. This 
could  create  a  further  burden  that  would  not  be  applicable  in  relation  to  human 
medicinal products. 

Acceptance 

CAs from eight Member States have expressed their support for the development of a 
centralised API monograph system. No other stakeholders expressed positions. 

Industry  has  already  invested  in  establishing  ERAs  for  most  generics  and  originator 
products  and  is  strongly  concerned  about  reassessment  and  the  additional  costs  that  a 
monograph system would bring. As mentioned before, industry considers that the costs 
and  resources  needed  for  a  monograph  system  are  largely  under-estimated  in  the 

EN 

10 

EN 

 
feasibility  study  and  the  respective  report  does  not  consider  nor  address  the  practical 
hurdles linked to the implementation of a monograph system. 

Revision of the legal framework 

Introducing the monograph system  would necessitate amendments  of Regulation  (EU) 
2019/6  as  outlined  in  the  MONO4ERA  proposal.  This  would  include,  for  instance, 
introducing  requirements  for  applicants  to  provide  a  draft  monograph  as  part  of  the 
technical documentation referred to in Article 8(1)(b) in conjunction with Annex II; for 
MAHs of existing VMPs to jointly generate, use and submit environmental information 
to the CAs; for sharing the monographs among MAHs; for the Commission to adopt a 
programme for the gradual establishment of monographs for APIs already on the market 
(catch-up procedure) and prioritisation of APIs; for regular updates of the monographs 
as  part  of  the  obligations  of  MAHs  under  Article 58;  for  data  protection;  for  the 
monograph  database;  as  well  as  for  sanctions  under  Article 130(3)  for  failure  to  fulfil 
the obligations regarding the establishment of monographs. 

In  theory,  both  alternative  systems  (AhE  and  Access VetMed)  could  be  put  in  place 
without a revision of the current legal framework. However, in practice, the success of 
both  systems  would  depend  entirely  on  the  willingness  of  the  CAs  to  conduct  the 
necessary  work.  In  the  absence  of  a  clear  legal  framework  imposing  a  timeline,  a 
common approach and prioritisation of the effort by the CAs, both proposals are likely 
not to work. 

All three systems proposed would thus require a revision of the current legal framework 
for VMPs. 

6.  CONCLUSIONS 

The active-substance-based monograph system and the two alternatives that have been 
evaluated could to varying degrees contribute to improving environmental protection. 

The  monograph  system  would  best  optimise,  improve  and  consolidate  hazard  data  on 
active  substances  for  ERA,  improve  knowledge  about  relevant  environmental  risks, 
avoid  duplication  of  tests  on  vertebrate  animals  and  thus  contribute  to  the  3  R’s 
(Replace, Reduce, Refine), lead to  a higher quality of ERA data, allow environmental 
information  to  be  gained  more  efficiently  and  give  environmental  authorities,  experts 
and the public access to  ERA data. In the long term, the administrative burden on the 
authorities and industry is expected to be reduced. However, this effect of reducing the 
administrative burden is not guaranteed20. 

The  monograph  system  would  enhance  the  protection  of  the  environment  thus 
supporting  one  of  the  main  objectives  of  Regulation  (EU)  2019/621.  Moreover,  the 
monograph system could ensure a consistent assessment of VMPs containing the same 
active substances. 

20  See section 4.2 – Administrative burden and cost for CAs. 
21  See  section  4.1  –  Guaranteeing  the  highest  level  of  protection  of  public  and  animal  health  and  of  the 

environment 

EN 

11 

EN 

 
                                                           
The  two  alternative  proposals  remain  centred  on  product  evaluation.  Therefore,  they 
would  not  address  some  of  the  drawbacks  of  the  current  system,  such  as  inconsistent 
assessments,  limited  availability  of  environmental  information,  and  the  remaining 
difficulty  to  identify  harmful  active  substances.  These  alternatives  would  not  result  in 
significant  improvements  regarding  protection  of  the  environment  and  of  animal  and 
human  health.  Moreover,  both  proposals  lack  clarity  on  the  timeline,  the  legal 
enforceability, how a harmonised approach between the CAs can be ensured and how 
the work should be prioritised. 

Therefore,  only  the  monograph  system  would  contribute  to  meeting  the  general 
objectives  of  Regulation  (EU)  2019/6  (except  for  the  envisaged  reduction  of 
administrative  burden,  at  least  initially)  and  support  the  EU  Strategic  Approach  to 
Pharmaceuticals in the Environment22 and the ‘one substance, one assessment’ approach 
as specified in the Green Deal23 and the Chemicals Strategy for Sustainability24. 

The monograph system represents a significant shift in the VMP authorisation process. 
The  changes  needed  for  the  implementation  of  a  monograph  system  (including  of 
legislative  nature),  would  be  a  major  challenge  for  the  veterinary  regulatory  network 
(CAs, EMA and the Commission) and the industry. 

During  the  implementation  phase,  the  monograph  system  and  the  two  proposed 
alternatives  would  give  rise  to  additional  costs  for  already  authorised  VMPs  and  are 
likely  to  be  more  cost-  and  resource-intensive  than  the  current  system  of  a  complete 
ERA evaluation for each individual VMP application. The costs for applicants of new 
MAs  of  VMPs  could  be  higher  under  the  monograph  system  in  comparison  with  the 
current  system  and the two alternatives  proposed. Consequently, a negative impact  on 
availability of VMP cannot be excluded and cost pressure on SMEs could increase. 

The  implementation  of  Regulation  (EU)  2019/6  is  still  developing.  It  calls  for  the 
adoption of some 25 delegated and implementing acts, about half of which needed to be 
adopted before or by the date of application, 28 January 2022. The next package of acts 
the Commission will focus on are mostly due by 2025, with one act due by 2027. Apart 
from  the legislative work, since the  adoption of  the Regulation  in  2018,  the resources 
and effort of the CAs and the industry have been directed at implementing the new legal 
framework  on  the  ground.  This  has  been  and  continues  to  be  very  demanding  and 
burdensome  for  the  network  and  the  industry.  Moreover,  the  effects  of  the  current 
system in relation to ERA, such as the impact of Article 18(7) on generic applications 
and Article 72 on legacy products that have not been subject to an ERA, will need time 
to materialise. Therefore, introducing the monograph system or any of the two proposed 
alternatives,  in  addition  to  the  measures  and  approaches  that  would  need  to  be  put  in 
place  in  order  to  implement  Regulation  (EU)  2019/6,  would  seem  to  be  premature  at 

22  COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE COUNCIL 
AND THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE European Union Strategic Approach to 
Pharmaceuticals in the Environment (COM/2019/128 final) 

23  COMMUNICATION  FROM  THE  COMMISSION  TO  THE  EUROPEAN  PARLIAMENT,  THE 
EUROPEAN COUNCIL, THE COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE 
AND THE COMMITTEE OF THE REGIONS The European Green Deal (COM/2019/640 final) 
24   COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE 

COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF 
THE REGIONS Chemicals Strategy for Sustainability Towards a Toxic-Free Environment. COM(2020) 667 
final 

EN 

12 

EN 

 
                                                           
this  point  in  time  and  would  impose  excessive  demands  on  already  overstretched 
resources. 

The  implementation  of  a  monograph  system  could  be  reconsidered  once  Regulation 
(EU) 2019/6 is completely implemented and its impacts in practice (i.e., availability of 
VMPs, administrative burden, impact of SPC harmonisation etc.) become clearer. This 
would then also require more certainty on the costs linked to the implementation of such 
an active-substance-based system and its further impacts on the availability of VMPs. 

In order to have a comprehensive and coherent system, the monograph system must be 
considered in a broader context, beyond the VMP sector. In light of the overall number 
of  APIs  in  medicinal  products  on  the  EU  market25,  a  system  collecting  the 
environmental data of those used in VMPs would only cover a small portion of the APIs 
on the market and result in an incomplete database. 

The  ongoing  work  on  a  future  Commission  proposal  to  revise  the  general  legal 
framework for human medicinal products would likely include new ERA requirements. 
Therefore,  it  is  appropriate  to  wait  for  the  outcome  of  this  process  before  considering 
implementing the monograph system for VMPs. 

In the meantime, the Commission will explore, in close cooperation with the CAs, the 
possibilities  to  improve  and  harmonise  the  current  system  as  much  as  possible. 
Measures  could  be  agreed  upon  to  facilitate  the  potential  future  implementation  of  a 
monograph  system,  without  impacting  the  workload  of  the  CAs  nor  requiring  any 
change to the existing legal framework. 

25  See Background section. 

EN 

13 

EN 

 
 
 
                                                           
LIST OF ABREVIATIONS 

AhE 

AnimalhealthEurope 

AMR   

Antimicrobial Resistance 

API 

CA 

Active Pharmaceutical Ingredient 

Competent Authority 

EICaquatic 

Environmental Introduction Concentration in water 

EMA   

European Medicines Agency 

(E)PAR 

(European) Public Assessment Report 

ERA 

MA 

Environmental Risk Assessment 

Marketing Authorisation 

MAH   

Marketing Authorisation Holder 

PECSOIL 

Predicted Environmental Concentration in soil 

PBT 

Persistent, Bioaccumulative, and Toxic 

RMM   

Risk Mitigation Measures 

SPC 

UPD 

Summary of Product Characteristics 

Union Product Database 

VICH   

Veterinary International Conference on Harmonisation 

VMP 

Veterinary Medicinal Product 

EN 

14 

EN