Biological VMPs: EU perspective 18th VICH Forum

Regulation (EU) 2019/6 on VMPs Article 4 Definitions:

(5) ‘immunological veterinary medicinal product’ means a veterinary medicinal product intended to be administered to an animal in order to produce active or passive immunity or to diagnose its state of immunity;
(6) ‘biological veterinary medicinal product’ means a veterinary medicinal product where an active substance is a biological substance;
(7) ‘biological substance’ means a substance that is produced by or extracted from a biological source and that needs for its characterisation and the determination of its quality a combination of physico-chemical-biological testing, together with knowledge of the production process and its control. 4 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Registration of biological VMPs in the EU In the EU, the term ‘biologicals’ encompasses both ‘immunological’ and ‘biological other than immunological’ VMPs. Legal definitions apply, and dossier requirements vary depending on the product classification. 5 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Immunological VMP Biological other than immunological VMP Article 4 (5), ‘immunological’ VMP;
Annex II, section IIIb, requirements for immunological. Article 4 (6), ‘biological’ VMP;
Article 4 (7), ‘biological substance’;
Annex II, section IIIa, requirements for biological VMPs other than immunological VMPs. Regulation (EU) 2019/6<br>

Equivalent dossier structure:

Part 1: summary of the dossier
Part 2: quality documentation
Part 3: safety documentation
Part 4: efficacy documentation 6 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Key technical differences in dossier requirements Critical observations:
IIIa dossiers are chemically and structurally intensive, reflecting the complexity and diversity of non-immunological biologicals.
Regulatory flexibility is greater in IIIa, allowing scientific justification for deviations due to product-specific properties.
IIIb dossiers are biologically and immunologically focused, prioritising immune response and field applicability.
IIIb has more standardised expectations, especially for vaccines, due to public health implications and harmonisation needs.<br>

Key technical differences in dossier requirements 7 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Key technical differences in dossier requirements 8 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Key technical differences in dossier requirements 9 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Implications for dossier preparation 10 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

General overview of the registration process 11 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Eligibility request
Up to 7 months before submission of MAA (marketing authorisation application) Notification of intention to submit
4 months before submission of MAA Appointment of rapporteurs
4 months before submission of MAA Scientific evaluation
Up to 210 active days of assessment Submission and validation
As per legal requirements and deadlines Pre-submission meeting CVMP opinion European Commission decision
Within 67 days<br>

12 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Approaches to registration of veterinary vaccines: modularity<br>

- A stand-alone MAA section containing all quality data for an antigen; shared across one or more MAs
- Can be part of an initial MAA or presented as a separate procedure
- Centralised evaluation handled by EMA
- VAMF certificate valid EU-wide, for any authorisation route; can be used in support of future applications using the same antigen 13 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Available regulatory tools: VAMF (vaccine antigen master file) Pt 2: Antigen B Pt 2: Antigen C Vaccine 1 Pt 2: Antigen D Vaccine 2 Pt 2: Antigen E Pt 2: Antigen F Vaccine 3 … Pt 2: Antigen G<br>

14 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Available regulatory tools: vPTMF (vaccine platform technology master file) - Technologies using a common backbone/vector, can be modified with different antigens/inserts per vaccine
- Can be part of an initial MAA or presented as a separate procedure
- Stand-alone MAA section containing all shared data across platform-based vaccines (Q-S-E)
- Centralised evaluation handled by EMA
- vPTMF certificate valid EU-wide, for any authorisation route; can be used in support of future applications using the same platform Vaccine 1<br>

Available regulatory tools: VAMF and vPTMF 15 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA OVERALL BENEFITS
Single dossier / assessment
Speeds up assessment; data not reassessed
Increase predictability
vPTMFs fosters use of PT for development of vaccines & reduces data requirements when PT is used. EMA GUIDANCE AVAILABLE
Procedural advice for VAMF certification and vPTMF
Guideline on data requirements for VAMF certification and vPTMF MODULARITY PORTABILITY/REUSABILITY DECREASED ADMINISTRATIVE BURDEN<br>

- A single MA dossier with data for different antigens/strains allowing different combinations of final formulation adapted to the epidemiological situation
- Any inactivated vaccine against antigenically variable viruses or bacteria requiring rapid or frequent change in composition
- Each dossier is only applicable to one virus species, bacteria genus or vector
- Eligibility for the MS approach to be confirmed by EMA, but not necessary for vaccines against FMD, AI, BTV and diseases for which a MS dossier has already been authorised 16 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Available regulatory tools: Multi-strain dossier Antigen B Antigen C Vaccine 1 Antigen B Antigen C Antigen D Antigen E Antigen F Antigen C Vaccine 1 Antigen D Vaccine 1 Antigen B Antigen E Antigen F …<br>

vladimir.pucovsky@ema.europa.eu<br>

18 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Back-up slides<br>

Regulation (EU) 2019/6 on VMPs Annex II Requirements referred to in Article 8(1), point (b):

Section III. Requirements for biological veterinary medicinal products:
Section IIIa. Requirements for biological veterinary medicinal products other than immunological veterinary medicinal products;
Section IIIb. Requirements for immunological veterinary medicinal products. 19 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

General support of innovation 20 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Novel Therapies & Technologies Working Party (NTWP):
develops guidelines for novel veterinary therapies
advises on data requirements for evaluating quality, safety, and efficacy of novel therapies, including post-authorisation evidence, where applicable
contributes to regulatory science strategies for improved access to innovation
facilitates ongoing dialogue with relevant stakeholders and interested parties<br>

General support of innovation 21 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Supporting SMEs (small, medium and micro enterprises) with a dedicated office to promote innovation and development of new medicines by:
giving regulatory, administrative and procedural support
facilitating communication
fee incentives,
translation assistance
training and awareness<br>

General support of innovation 22 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Innovation Task Force (ITF), a team combining scientific, regulatory, and legal expertise supporting emerging therapies and technologies:
Briefing meetings: a platform for early dialogue with applicants to identify potential challenges
enable informal early-stage guidance and information exchange
involve experts from EMA and NCAs, committees, and working parties
complement and strengthen formal regulatory procedures
free of charge<br>

General support of innovation 23 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Veterinary limited market products are defined in Regulation (EU) 2019/6 Article 4(29) as:
VMPs for the treatment or prevention of diseases that occur infrequently or in limited geographical areas
VMPs for animal species other than cattle, sheep for meat production, pigs, chickens, dogs and cats

If the benefit of the availability on the market of the veterinary medicinal product to the animal or public health outweighs the risk inherent in the fact that certain documentation has not been provided, applicants shall not be required to provide the comprehensive safety or efficacy documentation required in accordance with Annex II.<br>

General support of innovation 24 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Scientific advice is provided by CVMP and entails a fee:
product-specific
a 60-90 days’ procedure after validation
generally requested during the development of the VMP, sometimes for post-authorisation procedures
questions to the CVMP, addressing specific issues related to quality, safety, efficacy/clinical development, MRLs, or bioequivalence<br>

General support of innovation 25 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Pre-submission meetings are aimed at supporting applicants in the finalisation of their marketing authorisation applications:
address product-specific legal, procedural, and regulatory issues,
applicant-initiated, ideally 6-7 months before submission,
can also occur earlier in development,
non-binding advice, does not influence CVMP’s assessment,
free of charge.<br>

26 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Quality Safety Efficacy Pharmaceutical Biological not immunological Immunological Key technical differences in dossier requirements<br>

27 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Stability of biologicals<br>

Stability tests Dossier requirement as per Annex II (sections IIIa.2G and IIIb.2G).
Stability testing applies to both the active substance and the finished product, including solvents if relevant.
Real-time studies are mandatory. 28 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Stability tests – key requirements 1. Storage conditions and shelf-life:
define intended storage conditions and duration based on stability data,
may be derived from testing either the active substance or the finished product.
2. Testing protocol:
conduct tests on at least three representative batches,
use final container(s) for storage,
include biological and physicochemical stability tests at regular intervals.
3. Conclusions and specifications:
provide analytical results justifying shelf life under proposed conditions,
use results to define formulation and release specifications. 29 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Stability tests – key requirements 4. Special use cases:
products administered in feed: shelf life at different mixing stages must be provided,
products requiring reconstitution or administered in drinking water: shelf life of reconstituted product must be supported by data,
multi-dose containers: provide stability data post-opening and define in-use specifications.
5. Degradation and preservatives:
declare degradation products and describe identification/test methods,
demonstrate preservative efficacy; data from similar products may suffice.
6. Combined products:
stability data from combined products may be used for derivatives if justified. 30 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

Stability tests – comparison between IIIa and IIIb 31 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA<br>

32 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA FMD vaccines<br>

Foot-and-Mouth Disease (FMD) 33 Biological VMPs: EU perspective. 18th VICH Forum meeting – Indianapolis, USA Foot-and-Mouth Disease (FMD) is classified as a Category A disease under the EU Animal Health Law. It is not normally present in the EU, and immediate eradication is required upon detection.
An outbreak causes major production losses and trade disruptions due to movement restrictions and control measures. The EU has harmonised rules for outbreak response, including culling of susceptible animals, safe disposal, and thorough cleaning and disinfection. Zoning rules apply.
Vaccines are available but take time to build immunity and may impact trade. Preventive vaccination is not allowed in disease-free Member States; national authorities decide on emergency use.
The European Commission supports Member States with:
one of the world’s largest FMD antigen banks,
a coordinated laboratory network led by the EU Reference Laboratory,
disease notification systems, and
a crisis management framework.<br>