News from National Competent Authorities Archives | European Regulatory Affairs Specialists

ERA at TOPRA 2025: Tailored development of biosimilars without efficacy and safety studies – is this the future?

3rd October 2025

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

ERA at TOPRA 2025: Session 8 – Human – ePI is on Fire! (I mean FHIR !!)

1st October 2025

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

ERA at TOPRA 2025: Session 6 – Human – How AI is Transforming Regulatory Approaches towards CMC

30th September 2025

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

https://www.gov.uk/government/news/mhra-showcases-next-phase-of-regulatory-science-to-bring-innovative-treatments-to-patients-sooner

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

ERA at TOPRA 2025: Session 5 – Human – Programme COMBINE – Clinical Trials with Medicine + Medical Device

30th September 2025

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

ERA at TOPRA 2025: Session 4 – Human – Revision of the EU variation Regulation

30th September 2025

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

ERA at TOPRA 2025: Session 3 – Human – Applying Artificial Intelligence in Real-Life

30th September 2025

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

ERA at TOPRA 2025: Session 1 – Human – General Pharmaceutical Legislation – Sandbox

29th September 2025

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.

https://www.ema.europa.eu/en/human-regulatory-overview/research-development/innovation-task-force-briefing-meetings#how-to-apply-76207

Points to note:

Foreseen for MAA only at present
R&D with Industry, Regulators, Patients and Academia involved
Masterfile concept
Patent protections to be considered in advance

Written by

Alice D’Alton

Alice Dalton 1

Type IA Annual Reporting in the UK

13th May 2025

Following on from our News Article: “You need to apply Type IA Annual Reporting in the EU in 2025” we can further advise that the MHRA has also adopted the EU changes in relation to Type IA variations for UK products.

This means that the MHRA do also require the submission of Annual Updates for Type IA variations, and these should be submitted nationally, unless the Type IA variations are submitted as part of a group with other variations applied for via the International Recognition Procedure (IRP).

IRP Variations:

You can use IRP during the lifecycle of UK products that have been initially authorised or subsequently varied via standalone;

National route
Decentralised and mutual recognition reliance procedure (MRDCRP) route
European Commission (EC) Decision Reliance Procedure (ECDRP) route

Conversely, where a product has been authorised via IRP, it is acceptable to submit standalone national post-authorisation procedures, including variations.

Variations submitted via IRP should be classified according to MHRA guidance on variations to MAs. To facilitate lifecycle management of the MA, variations should be submitted as soon as possible after approval by the Reference Regulator (RR).

The MHRA will be publishing updated guidance on Annual Updates very shorty. So, watch this space for a more detailed overview when it becomes available.

Written by

Fiona Downey

Fiona Downey 1

MHRA – Pharmacovigilance – Categories 1 and 2 medicinal products

24th March 2025

The Windsor Framework changed the regulation of medicinal products that were formerly in the scope of the EU centralised procedure so that these products are now licensed UK-wide under UK law.

Products not within this scope are authorised UK-wide under UK and applicable EU law (as amended by Regulation (EU) 2023/1182 and Directive (EU) 2022/642), as has been the case since 1 January 2021.

As a result, UK authorised products are now placed into one of two Categories:

Category 1 are UK products which fall under the mandatory or optional scope of the EU Centrally Authorised Procedure.

Category 2 are UK products which do not fall within the scope of Category 1 will be Category 2 products.

To assist MAHs in verifying the category of each of their products, a decision ladder has been created by the MHRA. The MHRA has also publish lists of Category 1 products and Category 2 products.

Which category your product falls under, will decide the pharmacovigilance requirements of that product.

Category 1 will be subject to UK legislation only. These products will legally be required to follow Part 11 of the HMRs for pharmacovigilance.

Category 2 will be subject to UK and EU requirements as applicable. These products will be legally required to follow Part 11 of the HMRs for pharmacovigilance with further pharmacovigilance requirements outlined in Schedule 12A of the HMRs.

However, it should be note that all existing exemptions that apply to all UK medicines remain in place irrespective of Category.

The MHRA has published Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK marketing authorisation holders and the licensing authority which outlines the requirements of products classed as Category 1 or 2, they have also published guidelines to clarify ICSRs reporting and PSUR submissions requirements for each category.

If you need assistance with any of the above or anything Windsor Framework related, please free feel to contact us.

Written By

Fiona Downey

Fiona Downey 1

Back to Basics – The Risk Management Plan (RMP)

19th July 2024

The Risk Management Plan (RMP) documents the risk management system considered necessary to identify, characterise and minimise a medicinal product’s important risks.

The RMP should be updated throughout the life cycle of the product, for example;

if there is a change in the list of the safety concerns
when there is a significant change in the existing additional pharmacovigilance activities
if an emerging safety issue is confirmed.

The RMP should be assigned a new RMP version number and a date each time it is updated and submitted for assessment.

An updated RMP can be submitted as a standalone [currently C.I.11] variation, when necessary, but it is most often submitted as a consequence of or part of another variation.

The format and content of the RMP should follow the RMP template; Guidance on the format of the risk management plan (RMP) in the EU – in integrated format which consists of seven parts.

For a generic medicinal product, hybrid products and/or fixed combination products with no new active substance the safety concerns should be aligned to those of the originator product that are available;

either from the originator’s approved RMP
or from the list of safety concerns of the substance published on the CMDh website.

RMPs are approved per each medicinal product, not per MAH, therefore only one RMP should be submitted for an MRP or DCP with different MAHs. The RMP must remain identical in RMS/all CMS throughout the product life cycle.

The RMP should be provided in eCTD section 1.8.2. To facilitate the assessment a ‘tracked changes’ version of the RMP, in Microsoft word, should also be provided in the ‘working-documents’ folder outside eCTD.

The QPPV’s actual signature or the evidence that the RMP was reviewed and approved by the QPPV should be included in the finalised approved version of the document; for eCTD submissions this would be the RMP submitted with the last eCTD sequence of the procedure (usually the closing sequence).

UK RMP: The MHRA states you can either submit a GB/UK RMP or use the approved EU RMP with the GB/UK specific annex attached. Further information of UK RMP can be found on the MHRA website and their Guidance note on good pharmacovigilance practices.

Feel free to contact us here at ERA to assist you with all things regulatory in Ireland, UK and across the EU.

We take the pain out of regulatory so that you can take your medicine to the next level.

Written by

Fiona Downey

Fiona Downey 1

ERA at TOPRA 2025: Tailored development of biosimilars without efficacy and safety studies – is this the future?

ERA at TOPRA 2025: Session 8 – Human – ePI is on Fire! (I mean FHIR !!)

ERA at TOPRA 2025: Session 6 – Human – How AI is Transforming Regulatory Approaches towards CMC

ERA at TOPRA 2025: Session 5 – Human – Programme COMBINE – Clinical Trials with Medicine + Medical Device

ERA at TOPRA 2025: Session 4 – Human – Revision of the EU variation Regulation

ERA at TOPRA 2025: Session 3 – Human – Applying Artificial Intelligence in Real-Life

ERA at TOPRA 2025: Session 1 – Human – General Pharmaceutical Legislation – Sandbox

Type IA Annual Reporting in the UK

MHRA – Pharmacovigilance – Categories 1 and 2 medicinal products

Back to Basics – The Risk Management Plan (RMP)

Need help with all the regulatory jargon?

Links

Our Policy

Find Us