With growing experience and coverage of the biosimilar market, regulatory strategies must evolve to balance scientific rigor with the need for efficient development.
One of the currently most debated topics in the biosimilar arena is the potential waiver for traditional efficacy and safety studies, a move that could significantly reduce development timelines and costs.
This session focused on the increasing interest in shifting the emphasis to establish similarity mainly based on CMC comparability data, as opposed to relying on results from comparative clinical efficacy trials (CES).
The session explored the scientific rationale behind using robust CMC evidence as the cornerstone of biosimilar approval, while addressing concerns regarding the adequacy of clinical data.
Experts in CMC presented their views on how advanced manufacturing technologies, analytical techniques, and product characterization can generate the necessary evidence to support a waiver for extensive efficacy and safety studies. These experts shared insights on how consistent manufacturing and comparability of biosimilars can be sufficiently demonstrated through state-of-the-art analytical methods, highlighting the potential for regulatory flexibility in this area.
On the other hand, clinical specialists provided arguments from a clinical point of view, discussing the feasibility and concerns about the lack of efficacy and safety data in these developments. They examined the implications of waiving clinical trials, particularly in terms of patient safety, real world outcomes, and public confidence in biosimilars.
By bringing together experts from both the CMC and clinical fields, this session provided a comprehensive, balanced view of the challenges and opportunities in biosimilar development.
Points to note:
There is 20 years of experience now in EU (both Industry and Regulators)
Are Clinical efficacy studies (CES) still needed?
Analytical tools are more sensitive to detect differences than CES.
CES can not always contribute relevantly to decision making and could not solve PK issues
Trials can cost $100-$300 million dollars
Biosimilar void is coming (many products off patent soon with no generics in development)
Regulators are getting ready for less clinical data to make decisions (when appropriate)
You do need a comparative PK study, supportive safety/immunogenicity data, CES may only be needed to answer outstanding scientific questions
Quality and Non-clinical evidence grounded in comparability (ICH Q5E) – better knowledge of mode of action today than before
EMA/CHMP/BMWP/60916/2025 (Reflection paper – https://www.ema.europa.eu/en/reflection-paper-tailored-clinical-approach-biosimilar-development)
EMA/CHMP/138502/2017 (Reflection paper – https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-statistical-methodology-comparative-assessment-quality-attributes-drug-development_en.pdf – use it for discussion and clarification with Regulators. It won’t always be applicable to your product)
Impacts on potency (discussion in dossier required), Critical Quality Attributes (CQA) risk ranking approach (examples given on how to justify)
Quality of Reference Product can differ over time and so needs to be monitored by R&D, PK/PD study data becomes essential when CES is excluded.
Protein quantity similarity assessment is necessary
PK/PD could be used to supplement immunogenicity data requirements (via better assays)
Ask Regulators not to get bogged down in differences that don’t matter (convince them in your submission)
EMA perspective:
Quality data has evolved
Reflection paper on statistics is a tool box of options (not a requirement).
Industry should use Quality data as appropriate.
Immunogenicity topic is still under discussion at EMA.
Structural analysis needs to be robust, guideline for biosimilars is being developed.
Q&A:
Discuss CES requirement with EMA in scientific advice – Application must be mature enough to allow for Regulator advice, see reflection paper – Approach them after batch manufacture once you can see how things are aligning
Prescribers may need help to accept Biosimilars approved without CES.
IPRP workshop was valuable (https://admin.iprp.global/sites/default/files/2024-07/IPRP_BWG_Final%20IPRP%20Scientific%20Workshop%20Summary%20Report_2024_0506.pdf)
Wider community is pretty open to waivers, follow-up with NCA initiated (Reflection paper).
WHO guidance is already followed by many countries and also mentions CES waiver.
Written by
Alice D’Alton
Alice Dalton 1
https://eureg.ie/wp-content/uploads/2025/09/ERA-logo-with-TOPRA-info-25-09-25-e1758811589325.png8671300ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2025-10-03 11:37:182025-10-03 11:37:18ERA at TOPRA 2025: Tailored development of biosimilars without efficacy and safety studies – is this the future?
This session focused on the regulatory implications and readiness strategies for the implementation of electronic Product Information (ePI) based on the HL7 FHIR® standard.
As outlined in the EU pharmaceutical strategy and reinforced by EMA’s digital initiatives, the structured, interoperable ePI format will play a critical role in improving the accessibility, reliability, and lifecycle management of product information.
Regulatory authorities and marketing authorisation holders must prepare for changes in submission formats, review procedures, and data governance models.
The session provided an overview of current status of the EU ePI project including linking to ePI from EU medicine packages, regulatory frameworks, and anticipated timelines.
Practical insights were shared on how regulatory professionals can adapt internal processes and evaluate IT infrastructure needs to ensure compliance and facilitate the seamless integration of FHIR-based ePI into existing regulatory operations.
Points to note:
Guidance on PLM portal (incl style guide). ePI pilot report available. Reflection paper published Q2-2025. You Tube videos. Quarterly system demos ongoing
Free software from regulators via PLM portal. Pilot showed it took just 4 hours for a company to create ePI from scratch using these tools
Technology used is the FHIR common standard for healthcare data exchange. Harmonised EU approach. PLM portal storage and access (FHIR repository)
User testing would still be required in some form in future
Better supply chain management for industry
73% of delegates at this session said their company have not implemented any ePI process yet
ePI will be submitted as additional material alongside word and pdf version for assessment (for a while)
Once ePI is approved it is put into the central repository and then is available to the patient for download
Go live for CAPs and early adoption NCA is planned soon (ePI type 1) – likely with New legislation implementation (~2028) – implementing act may have more specific information to clarify ePI requirements
What does the future look like?: ePI type 4 is under development (ePI 2 & ePI 3 exist but not implemented). ePI type 5 is in the idea stage
ePI is already implemented in other jurisdictions so EU needs to catch up
Written by
Alice D’Alton
Alice Dalton 1
https://eureg.ie/wp-content/uploads/2025/09/ERA-logo-with-TOPRA-info-25-09-25-e1758811589325.png8671300ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2025-10-01 10:24:192025-10-01 10:24:19ERA at TOPRA 2025: Session 8 – Human – ePI is on Fire! (I mean FHIR !!)
This session explored the transformative role of Digital tools including Artificial Intelligence (AI) in enhancing Chemistry, Manufacturing, and Controls (CMC) processes within the pharmaceutical industry.
As AI technologies continue to advance, their integration into CMC activities offers exciting opportunities to streamline development, optimize manufacturing, and improve regulatory decision-making.
Points to note:
The Quality Innovation Group (QIG) supports the development of new technologies throughout the product lifecycle. They want to collaborate with as many groups (regulators) as possible to avoid silos (contact qig@ema.europa.eu)
Revision of EU GMP guide Annex 11, 22 and Chapter 4 ongoing (all under stakeholder consultation – comments by 7th October)
New Annex 22 does not cover Generative AI or Large Language Model (LLM). Detailed overview of the requirements and expectation were presented
UK: Centres of Excellence for Regulatory Science and Innovation (CERSIs) & MHRA – Regulatory science and innovation network. They are looking at the regulatory challenges that are slowing the adoption, and realising of the full potential of, digital tools so they can be used in lieu of generating new data. Using VERA (virtual assistant) to find and review content of documents they already have
Digital CMC sandbox for testing digital tools in a safe place
Industry perspective: using models whenever possible and LLM, GenAI, Deep Learning (DL), Neural Network (NN) for e.g. visual inspection on production floor, Machine Learning (ML).
EMA/90634/2024 guidance – decision tree under consultation
Risk management approach to AI (EU AI act)
ISPE guideline 2025 – use in parallel with GAMP 5 (2022)
Panel discussion: Models already used in manufacturing for years, AI is an evolution of digital tools already being used (not a revolution)
AI being used to generate annual product reviews, analysis of trends.
Regulators are exploring possibilities of using AI for CMC review (there is potential)
Industry needs Regulators around the world to accept the data generated or it will not be cost effective to implement process modelling technology
Training will be critical
Written by
Alice D’Alton
Alice Dalton 1
https://eureg.ie/wp-content/uploads/2025/09/ERA-logo-with-TOPRA-info-25-09-25-e1758811589325.png8671300ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2025-09-30 15:01:262025-10-01 09:16:01ERA at TOPRA 2025: Session 6 – Human – How AI is Transforming Regulatory Approaches towards CMC
This session looked into opportunities and challenges with application procedures when performing a combined clinical trial in Europe, that involves a medicinal product and an in vitro diagnostic (IVD), or companion diagnostic (CDx) and/or a medical device (MD) component.
The clinical trial application for the medicinal product is submitted under the Clinical Trial Regulation (CTR) via CTIS, while the device/diagnostic follows different national procedures.
An update on the COMBINE project was provided.
The device regulation (MDR and IVDR) has introduced major changes and has been suggested as a contributing factor to the decrease in the number of clinical trials in Europe.
The European Commission and EU Member States have launched the COMBINE initiative to propose solutions for combined trials (drug using a device in a clinical trial), specifically looking at the interplay of IVDR, MDR and CTR, also identified as one of “most important issues” by stakeholders ACT-EU workplan ‘25-’26.
The panel discussion explored whether the proposed solutions stemming from this highly welcomed initiative are already demonstrating benefits. It also offered concrete strategies to ensure the European clinical trial ecosystem is well-suited to promote the conduct of clinical trials in Europe.
Points to note:
Guidance will be published but in the meantime please seek scientific advice
The COMBINE project team would like to see devices included in the Regulatory sandbox concept
There are 8 applications in the pilot phase of COMBINE already
UK involvement in the project could be beneficial in order to manage the complex requirements currently in place for Northern Ireland and to encourage clinical trials to be located there.
Written by
Alice D’Alton
Alice Dalton 1
https://eureg.ie/wp-content/uploads/2025/09/ERA-logo-with-TOPRA-info-25-09-25-e1758811589325.png8671300ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2025-09-30 14:59:342025-09-30 14:59:34ERA at TOPRA 2025: Session 5 – Human – Programme COMBINE – Clinical Trials with Medicine + Medical Device
The EU variation Regulation was updated in March 2024 and the new Detailed guideline for classification of variations [last dated from 2008, last update 2013] was published this month.
Nevertheless, this is the first step, limited by the current legislation, and a second step is awaited after the new EU general pharmaceutical regulation is in force (expected 2028).
The current European Commission updates simplify the requirements and procedures, modernise the framework, adapt the rules for grouping and work-sharing, adapt the classification for some products, reduce administrative burden, and implement a risk-based approach.
This session presented an overview of the original goals of the revision, the new changes in the management of post-approval changes; including a comparison of the previous and proposed classifications with statistics and impact for both regulators and industries in term of volume of variations being generated.
The session discussed opportunities to continue re-inventing both submission policies and processes for post-approval changes in the EU for centrally and nationally registered products.
Points to note:
Second revision will come with implementation of new Directive ~ 2028 and will aim to reduce the number of Type IA variations
Reinforcement of Annual Reporting and now mandatory worksharing (e.g. Update RMP, ASMFs, CEPs, etc.) discussed
Supergrouping can now include NAPs and Type IA variations
Worksharing (WS) now includes CAP, MR/DC and NAPs. New Declaration in eAF. Letter of Intent required.
MEB have seen significantly increased in WS applications. MEB is seeing a decline in IB variations already. Supergrouping applications have also increased in NL.
EMA Q&As are being compiled and will be published in Q4 2025 (e.g. Stability testing, classification of changes, skip/periodic testing, PLCM, etc.). More Q&As planned for Q1 2026
SPOR (referential lists) and eAF/PLM updates to follow
EMA encourages the use of the Change Management Protocol and hope to see it used more in future
Mandatory worksharing should be useful for both industry and Regulators, to increase efficiency and get faster approvals for multiple MAs
EMA allows the grouping of related IA and IAin despite the fact that variation regulation does not technically allow this (and it is not allowed for MR/DC), new guidance should help to clarify
Article 5 recommendations will remain as an option for variations that are not included in the new regulation
ICH Q12 should be reviewed in conjunction with new regulation and guidance
Written by
Alice D’Alton
Alice Dalton 1
https://eureg.ie/wp-content/uploads/2025/09/ERA-logo-with-TOPRA-info-25-09-25-e1758811589325.png8671300ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2025-09-30 10:14:482025-09-30 14:10:17ERA at TOPRA 2025: Session 4 – Human – Revision of the EU variation Regulation
Artificial Intelligence has already been a hot topic in numerous workshops, conferences, symposia and more in the past years. This session focused on questions such as:
How is it actually being applied in pharmaceutical development and regulation?
Where has it made the most impact in the field?
The session put aside the high-level discussions on what is possible with AI and discussed the real-life examples of where AI is already making a difference.
Points to note:
Auto dossier was presented and Demo shown of how it can automate CTD building
Collaborare: Unleashing the power of
patient voices using AI. This was presented and showed how patient voices can be added to decision making with AI tools
The Paul-Ehrlich Institut presented their ICSR processing tool and its benefits
The EMA presented its Signal detection tool and it benefits
Large Language models are routinely used today by industry and regulators to aid decision making and streamline their processes leaving more time for analysis and less time spent on admin, data collection and sorting
The AI workplan to 2028 is published – ‘Data and AI in medicines regulation
Fears of error introduced by AI was tempered by asking why we expect 100% accuracy from AI when humans do not output 100% accuracy all the time either
AI guidance from EMA will be principles based to future proof it as much as possible. Reflection papers will be followed by guidance in time
Written by
Alice D’Alton
Alice Dalton 1
https://eureg.ie/wp-content/uploads/2025/09/ERA-logo-with-TOPRA-info-25-09-25-e1758811589325.png8671300ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2025-09-30 09:12:022025-09-30 09:12:02ERA at TOPRA 2025: Session 3 – Human – Applying Artificial Intelligence in Real-Life
This session explored key elements of the EU General Pharmaceutical Legislation (GPL) that aim to foster innovation and accelerate patient access to new treatments. Key focus included Platform Technology approaches and Regulatory Sandboxes.
By bringing together perspectives from patients, regulators, legislators, academia and industry, the discussion highlighted how these regulatory tools can support cutting-edge pharmaceutical development and manufacturing while keeping the EU region competitive and attractive for innovation.
This session provided a comprehensive regulatory and scientific perspective on how these approaches can drive the future of pharmaceutical development in Europe, ensuring faster access to innovation while maintaining regulatory scientific robustness.
A regulatory sandbox is a controlled framework that allows the testing of an innovative development in a controlled environment for a limited period of time.
The creation of a regulatory sandbox might be necessary when it is not possible to develop a medicinal product unless targeted adaptations or derogations to certain requirements are applied, under direct supervision of the relevant competent authorities.
The EC legal proposal is still under discussion with the Parliament and Council, and a final decision on inclusion of the Regulatory Sandbox in the EU pharmaceutical framework has not yet been reached.
However, as part of the Agency’s monitoring horizon scanning on future innovative products, informal ITF meetings with medicine developers may help to identify, at an early stage during development, potential case studies that could inform a regulatory sandbox approach in the future (if endorsed by the co-legislators). These meetings are:
Early informal dialogue between medicine developers and regulators to gather information
Not a pre-assessment of product eligibility for a future regulatory sandbox approach or any other procedure.
So, let’s start with the Legal Basis which forms the first step of your MA application (MAA for short). You need to know the legal basis before you can finish compiling your application.
The legal requirements and necessary procedures for submitting an initial application for an EU marketing authorisation (MAA) are set out in Directive 2001/83/EC, as amended, and in Regulation (EEC) No. 726/2004 (the latter for CP applications).
The legal requirements for a UK MAA are set out in the Human Medicines Regulations.
The relevant articles and regulations from this legislation are provided below followed by a brief description of each legal basis:
1. Full/Complete
An application for a marketing authorisation (MAA) must be accompanied by the particulars set out in Article 8(3) of Directive 2001/83/EC, as amended, and as well as all the usual documentation will also require the results of
• Physico-chemical, biological or microbiological tests,
• Pharmacological and toxicological tests,
• Full Clinical trials in human subjects
This Legal basis is most often used for brand new medicines (Drug Product) or active substances (Drug Substance) which have never been authorised in EU or UK before. It results in 10 years or 8+2+1 years of data exclusivity. No generic version can be marked until this exclusivity expires.
2. Generic
This is used when the medicinal product (Drug Product) for which an MA is sought is considered essentially similar to and interchangeable with a medicinal product that has already been authorised via Article 8(3) in the EU or UK.
Essentially similar means it has the same active substance, the same amount of active substance (strength), and the same pharmaceutical form.
In this case the Applicant cross refers to an already approved EU/UK reference medicinal product (RMP for short) to use its already approved data on the Pharmaco-toxicological and Clinical aspects of the application and so does not need to repeat these trials. Instead a bioequivalence study in human subjects is required. This data will show that the product is safe and works the same way inside the human body as the RMP does.
3. Hybrid
These are applications which rely on a mixture of data – i.e. a cross reference to the RMP for some aspects of the clinical and pre-clinical data requirement plus provision of additional data in support of any aspect of the proposed drug product which is different to the RMP (i.e. where it is not essentially similar).
This type of application is used when the proposed product has a different/new indication, different/new dosage form, different/new strength, etc. that is not currently approved for the RMP.
4. Biosimilar
These are generic products which are derived from a biological source rather than a chemically synthesised molecule.
It is often difficult to treat biosimilar generic products in the same way as we treat ‘regular’ generics as it is very tricky to prove essential similarity in the conventional ways – therefore provision of some preclinical and clinical data may be necessary to prove safety and efficacy of the biosimilar product.
The Guideline on similar biological medicinal products should be consulted when considering using a non-EEA authorised comparator (i.e. a non- EEA authorised version of the RMP) in the development of a biosimilar.
5. Well Established Use/Bibliographical
It is possible to replace results of pharmacological and toxicological tests or clinical trials with detailed references to published scientific literature if it can be shown that the drug has a ‘well established use’ with recognised efficacy and known safety.
The minimum criterion for using this legal basis of application is that the drug substance concerned has to have been marketed (i.e. in use) in the EU for at least 10 years. It is commonly used when no RMP exists to refer to or to perform a bioequivalence study against.
This type of application, although allowed for under the legislation, is not always accepted by member states (and they have been known to request clinical data, during assessment) but with the use of real-world data and evidence on the increase this type of application may become more common. Only Time will tell.
6. Fixed Combination
In the case of new drug products containing known active ingredients (drug substances), not before used in combination for therapeutic purposes, the results of pharmacological and toxicological tests as well as clinical trials in human subjects, relating to that combination, must be provided.
This legal basis covers entirely new products that are a mixture of two or more drug substances (sometimes called monocomponents), which have already been authorised and marketed in the EU in their own right. Because this is theoretically a full, stand-alone application (not unlike Article 8(3)), the product enjoys the full 10 or 8+2+1 years data of exclusivity.
Please note that the concept of the global marketing authorisation applies here so once a combination is approved any new application(s) for the ‘same’ product cannot be considered new combinations anymore and so an article 10b would not be acceptable in this situation.
7. Informed consent/Duplicate
The Marketing Authorisation Holder (MAH for short) of a complete/standalone dossier (i.e. the originator/innovator/RMP) can consent in writing to allow a new applicant/MAH to refer to the contents of their approved MA (on file with Competent Authority) for the purpose of obtaining a new MA.
The reference dossier must be a complete dossier (Article 8(3)) and consent must be obtained for all three modules containing the pharmaceutical (Module 3), preclinical (Module 4) and clinical data (Module 5).
The Applicant must choose the correct legal basis in advance of submission and selecting the wrong one will delay your application.
If you need any clarification or support contact us and we will gladly assist you.
If you are starting out in Regulatory Affairs and you now have a long list of questions after reading this article, we can help. We provide detailed training for all levels of Regulatory experience. You or your manager can contact us for details and our training menu.
Written by
Fiona Downey 1
https://eureg.ie/wp-content/uploads/2023/11/Legal-basis.jpg10002000ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2023-11-23 20:50:292023-11-23 20:54:32Back to Basics – Regulatory 101 – Legal basis of your MA application in the EU and UK
A revised ICH Q3D guideline (R2) on ‘Elemental Impurities’ (EMA/CHMP/ICH/353369/2013) will come into effect on 24 September 2022.
The guideline is revised:
To amend permitted daily exposure (PDE)
To amend monographs
To add a section on limits for elemental impurities for cutaneous and transcutaneous formulations.
The revised guideline is available on the EMA website. You can find it by following this link
If Risk Assessment (RA) fails to demonstrate that an Elemental Impurities (EI) level is consistently less than the Control Threshold, then additional controls should be established to ensure that the EI levels does not exceed the PDE in the drug product.
Approaches that an applicant can pursue include but are not limited to:
Modification of the manufacturing steps that result in reduction of EIs,
Implementation of in-process controls,
Establishment of specification limits for excipients or drug substance or drug product,
Selection of appropriate container closure systems.
For marketed products, if the RA concludes that additional controls are to be established then the regulatory impact of these additional controls should be evaluated to see whether it triggers a variation(s) to the existing MA.
Ivowen is fully equipped to apply for any such variations on your behalf. Please contactus for more information and for support of your dossier compilation or updates.
Written by Nanda Naik
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The new veterinary regulation (NVR), Regulation 2019/6 applied to all EU Member States from 28 January 2022. The new legislation represents a significant change in how veterinary medicinal products are authorised, monitored and controlled in the EU.
The Regulation was developed in order to implement a fit-for-purpose veterinary legislation which would no longer be based on the equivalent human medicines authorisation system.
The new Regulation 2019/6 is broken down into the following chapters:
I. Subject matter, scope and definitions
II. Marketing authorisations
III. Procedures for marketing authorisations
IV. Post marketing authorisation measures
V. Homeopathic veterinary medicinal products
VI. Manufacturing, import and export
VII. Supply and use
VIII. Inspections and controls
IX. Restriction sand penalties
X. Regulatory network
XII. Common and procedural provisions
XII. Transitional and final provisions
Here is a summary of some of the noteworthy regulatory changes that have been introduced in chapters II, III & IV of the new veterinary regulation:
Chapter II – Marketing Authorisations:
An MA for a veterinary medicinal product shall be valid for an unlimited period of time. Hence, there is no longer a requirement for a renewal procedure or the sunset clause.
Chapter III – Procedures for marketing authorisations
Decentralised Procedure:
Scope and timelines remain unchanged
Responsibilities of RMS, CMS and applicant have changed at some steps of the procedure. For example,
– CMSs will also provide comments directly to the applicant at Day 100 and Day 145 instead of to the RMS only (therefore, comments are no longer anonymised).
– at Day 100-105 and Day 145-150, the applicant will now compile and circulate the LoQs.
– at Day 210, RMS will now be required to circulate a Final Assessment Report (FAR).
Scope remains the same. However, a minimum of six months is required between the decision granting the national MA and submission of an application for a MRP.
90 day procedure length remains unchanged but there are changes to some of the time-points in the procedure.
Responsibilities of RMS, CMS and applicant have changed at some steps of the procedure, similar to those outlined above for the DCP.
Centralised Procedure:
Scope of the mandatory use of the procedure has been widened. Refer to Article 42 (point no. 4) for details.
National Procedure:
No significant changes.
Subsequent Recognition Procedure (SRP):
Previously known as the “Repeat Use Procedure” is now officially recognised under Article 53 of the NVR.
Timelines and other requirements have been changed.
Due to the changes caused by the new regulation, CMDv have published updated guidance for DCP, MRP and SRP procedures:
Chapter IV: Post marketing authorisation measures (Variations)
In terms of variations to marketing authorisations, one of the main changes arising from Regulation EU 2019/6 is that instead of the previous categories of Type IA, IB and II variations there will now only be two categories of variations:
Variations Not Requiring Assessment = VNRA
Variations Requiring Assessment = VRA
VNRAs consist of all the previous type IA and some Type IB variation categories.
VRAs will consist of most of the previous Type IB and all of the Type II variation categories.
Commission Regulation 1234/2008 will now no longer apply to veterinary medicinal products due to the introduction of new veterinary regulation (2019/6).
Variations Not Requiring Assessment (VNRA)
The Implementing Regulation (EU) 2021/17*, includes a list of all variations not requiring assessment along with any associated conditions and documentation requirements and is published in the EU Official Journal here.
The variations are classified as follows:
Administrative changes
Changes to the quality part of the dossier
Changes to the safety, efficacy and pharmacovigilance part of the dossier
Changes to the vaccine antigen master file (VAMF) part of the dossier
VNRAs will be processed as follows:
The MAH will:
– Record the change in the Product Union Database (UPD) within 30 days of implementation including required documents (no application form is necessary).
– Documents submitted directly to UPD. No CESP submission. Documents include those listed in the Implementing Act as well as SPC, package leaflet, labels.
The relevant CA/RMS will
– Approve/reject the variation
– Inform MAH & CMS by recording decision in database and by e-mail
The format and categorisation is similar to the previous regulation which applied (Commission Regulation 1234/2008 ), however there are many differences.
The variations are divided into chapters as follows:
E. Administrative changes
F. Quality changes
G. Safety, Efficacy and Pharmacovigilance changes
H. VAMF or, PTMF changes
I. Changes of active substance(s), strength, pharmaceutical form, route of administration or food producing target species
Z-categories have also been included to address unlisted variations and VNRA, if requirements laid down in the Implementing Regulation are not met.
The timetable for VRAs is also outlined in the new guidance as follows:
a standard timetable, denoted by ‘S’ which will be 60 days
a reduced timetable, denoted by ‘R’ which will be 30 days
an extended timetable, denoted by ‘E’ which will be 90 days
For details on how to submit a VRA, CMDv have written a Best Practice Guide for Variations Requiring Assessment (EMA/CMDv/144277/2021). It has been prepared in order to facilitate the processing of VRAs for MRP/DCP products. The same general principles will apply to purely nationally authorised products.
Recommendation for the classification of variations not already listed
A procedure for requesting a recommendation for the classification of variations not already listed in either the above-mentioned Implementing Regulation or the EMA/CMDv Guidance on variations requiring assessment has also been established. This is similar to the previous CMDv recommendations for classification of unforeseen variations, according to Article 5 of Regulation 1234/2008.
Grouping and worksharing procedures do not apply to VNRA, they only apply to VRA.
As a consequence, no VNRAs can be included in a grouping or worksharing even if they are consequential or related to the VRAs included in the grouping or worksharing procedure.
However, the introduction section of CMDv Best Practice Guide for Variations Requiring Assessment (which also covers grouping), outlines the different approaches to follow when there is a need to co-ordinate changes that are related or consequential but are classified as VNRA and VRA.
The worksharing procedure is outlined in Article 65 of the NVR and it will be compulsory to follow this procedure, when the same change is being applied in different member states. Information related to worksharing is also mentioned in the CMDv BPG for Variations Requiring Assessment. However a specific guide on worksharing has also been written by CMDv: Best Practice Guide for Worksharing (EMA/CMDv/204024/2021).
Union Product Database
Due to the new regulation, the EMA has introduced new IT systems. The main one will be theUnion Product Database (UPD).
It will contain information for all authorised veterinary medicines in the EU (including all nationally authorised products). For MAHs, it will provide self-service access for specific regulatory activities, including the management of variationsthat do not require assessment.
For more information on implementation, training, registration and access of the UPD, refer to the following link here on the EMA website.
The UPD will be linked to the other 3 other databases in the future. These databases are at different stages of development and introduction:
Union Pharmacovigilance Database
On 28 January 2022, the Union Pharmacovigilance Database (EVV) was successfully released. User guidance and the release notes are available here.
Manufacturing and Wholesale Distribution Database
The Manufacturers and Wholesale Distributors database (MWD) was released on 28 January 2022. The system is an enhanced and upgraded version of EudraGMDP, the EU database of manufacturing authorisations and certificates of good manufacturing practice, with changes affecting both the veterinary and the human domains. The MWD Project Group has also adopted requirements for aligning the GDP module with the change made to the system so far. Changes to the module will be delivered in a subsequent release scheduled for Q1 2022. In addition, enhanced search facilities on the GMP module will be delivered in the same release.
Database for the Collection of Data on Sales and Use of Antimicrobials in Animals.
IT development on the Collection of Antimicrobials Sales and Use Data (ASU) project started in January 2022. Information on the progress of this project will be published on the EMA website as this project develops.
Q&A on transitional arrangements
CMDv has prepared a Q&A document in order to assist both MAHs and NCAs in the management of the transition between the requirements of Directive 2001/82/EC and Regulation (EU) 2019/6. This Q&A document will be regularly updated and can be found under the following link.
This document includes an Annex which outlines how individual Member States will handle renewals of marketing authorisations after 28 January 2022.
Should you need any support with Veterinary Procedures feel free to contact us & the Ivowen team will be here to help.
Written by Claire Brown
https://eureg.ie/wp-content/uploads/2022/04/Vet-article-feature-image-05-04-22.jpg6221106ERAadministratorhttps://eureg.ie/wp-content/uploads/2023/10/European-Regulatory-Affairs-Logo.svgERAadministrator2022-04-05 12:52:052023-11-06 11:18:32The new veterinary regulation (Regulation 2019/6) and its implications on regulatory submissions for veterinary medicinal products
