Guidance updates Archives | European Regulatory Affairs Specialists

ICH M4Q(R2): The Exciting Evolution of eCTD Modules 2.3 and 3.2

10th June 2026

ICH M4Q(R2), “The Common Technical Document for the Registration of Pharmaceuticals for Human Use” is a revised draft version of the guidance that outlines how the quality sections of your medicinal product dossier are presented.

ICH M4Q(R2) was signed off as a Step 2 document in May 2025. Public consultation closed in October 2025. In February 2026 an overview of the comments were published. It was 145 pages long! These comments will be taken into consideration by ICH M4Q (R2) Expert Working Group in the context of Step 3 of the ICH process. Step 4 is aimed to be adopted by June 2027.

The ICH M4Q(R2) revision marks an exciting evolution for eCTD Modules 2.3 and 3.2, modernising the Quality section to fully support emerging therapies and structured digital data.

Its objectives are to improve submission and assessment efficiency, resulting in accelerated access to pharmaceuticals by way of the six ‘E’s:

Encouraging global convergence of science- and risk-based regulatory approaches in the preparation of dossiers.
Explaining and defining the organisation and positioning of information for Modules 2 and 3.
Enriching communication between regulators and applicants and enhancing lifecycle and knowledge management.
Embracing product and process innovation.
Enabling efficient use of digital tools for submission and assessment and preparing for the closely linked, upcoming ICH guideline on structured pharmaceutical quality submission.
Elucidating regulatory expectations and supporting efficient assessments, decision making, and actions.

For industry, it hopes to

clarify regulatory expectations
facilitate the application of the enhanced ICH quality strategy/vision
streamline regulatory application preparation
improve the quality of submissions
facilitate data and information management
promote communication with regulators
and foster harmonisation and standardisation of data/information requirements for regulatory submissions, while increasing regulatory convergence

But what does this ICH update mean for you?

Module 2.3 will no longer just be a retrospective summary of Module 3. It will serve as the basis of regulatory assessment and will facilitate lifecycle management.

It will be a comprehensive overview of the product and core quality information. Its components will apply science- and risk-based principles.

Module 3 will serve as a repository for the detailed descriptions of methods, data, and other relevant quality information that supports Module 2.3

Most subsections will follow a ‘DMCS’ model:

Description: Identifies the material and its key characteristics;
Manufacture: Outlines the production process and process controls;
Control: Describes quality control measures such as specifications;
Storage: Provides container closure system, stability, storage condition, and retest period/shelf life.

Implementation

As you will see R2 is simply not just a reorganisation of information, it will require careful and detailed planning and efforts to implement. HOWEVER, clarification on transition and implementation timelines are awaited.

Future

Here at ERA, we will keep up to date on this topic, as it evolves, by attending workshops and webinars when they become available.

We hope to see the publication of clear guidance from the regulators and a pragmatic approach adopted (especially for legacy products). We wouldn’t say no to a nice little Q&A document either…

If you would like to discuss any of the above and if you need support with any of your future applications, we are ready to assist you and your team. Feel free to contact us and we will be happy to help.

Written by

Fiona Downey

Fiona Downey 1

1.Feature image Regulatory Guidance Updates, 08 01 25

Regulatory Guidance Updates in May 2026

8th June 2026

Did you know that the following Regulatory Guidance was updated in May 2026?

HPRA (IE):

Promoting medicines to the public on social media – the HPRA has launched a new webpage, setting out clear information on the laws that apply to advertising human medicines for the public
HPRA webinar – There will be a webinar hosted by the HPRA on the 19^th June 2026 on recent updates and developments in the veterinary medicine regulation

MHRA (UK):

Find product information about medicines page is updated to add
- Guidance with updated additional monitoring list April 2026
MHRA opens UK-wide consultation on redefining gene therapies on their proposed changes to how gene therapies are legally defined in UK legislation
- This will ensure UK regulation keeps up with advances in gene therapy, synthetic biology, and gene editing technologies
MHRA launched a public consultation on a proposed new Rare Disease Therapies Framework that would introduce significant regulatory innovation to the UK’s rare disease landscape
- MHRA is calling on the pharmaceutical and life sciences industries to play a central role in shaping the final framework.
MHRA welcomes submissions for participation in MHRA-NICE Real World Evidence Scientific Dialogue
- The expression of interest form is accessible since the 20 May 2026. Expression of interest guidance for applicants is also available
MHRA published the latest ‘conformity assessment routes flow chart’ to help companies conform with the legal requirements for placing medical devices on the market
MHRA request that current or potential Marketing Authorisation Holders (MAH) provide information on planned or potential future submissions to the MHRA
- Template spreadsheet (MS Excel) can be downloaded, filled in with as much information as possible and returned to the MHRA by email (where the information will be treated sensitively and securely)

EMA (EU wide):

As always the EMA regularly updates their website – here are some of the highlights from May 2026.

Medicines – Human:
- Revamp of marketing authorisation assessment templates
- Q&A on implementation of Ph. Eur. Medicinal Product Monographs (MPM)
- Updated questions and answers on periodic safety update report single-assessment (PSUSA): Guidance document for assessors
- Good manufacturing practice: Multistakeholder workshop on expert contributions to the artificial intelligence guidance development (Annex 22).
- Updated timetable for Initial (Full) marketing authorisation application – ATMP
- Updated timetable for accelerated assessment request for initial marketing authorisation applications
- Updated Product-specific bioequivalence guidance
Medicines – Veterinary:
- Updated QRD veterinary combined label-leaflet template v.9.1
- Updated guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 and on the documentation to be submitted pursuant to those variations
Upcoming Webinars:
- Clinical Trials Information System (CTIS): Information day will be provided by the EMA on the 17 June 2026 on-line
- Product Management Service (PMS): Information day will be provided by the EMA on the 09 June 2026 on-line
- Good Manufacturing Practice (GMP)/Good Distribution Practice (GDP) Inspectors Working Group is organising a two-day workshop on 30th June 2026 to help shape a risk-based approach to the use of generative artificial intelligence (AI) in medicines manufacturing.

CMDh (MRP/DCP):

Updated – list of active substances for which data has been submitted in accordance with Article 45 of the Paediatric Regulation
Contact Point List was updated
Updated – CMDh Guidance on the Informal Work-Sharing procedure for follow-up for PSUSA for NAPs (PSUFU procedure)
Correction to “Q&A – List for the submission of variations for human medicinal products according to Commission Regulation (EC) 1234/2008 as amended” to reflect the principles of Q&A 7.3.1. in the European Medicines Agency post authorisation procedural advice for users of the centralised procedure, which addresses the impact of changes in the clinical use of a product on quality documentation

eSubmissions:

Updates to web eAF (the most recent one released to production on 11 May 2026) is now available on the eSubmission PLM Portal eAF web page
As of 5 May 2026, the Readable IDs functionality is released within the European Shortages Monitoring Platform (ESMP). This improvement simplifies data entry, reduces the need for cross-referencing external lists, and enables more accurate verification of submitted information
- Live training recording & presentation: The training webinar held on 14 April 2026 introduced the readable IDs alongside other improvements, providing practical guidance to support day-to-day activities. EMA encourage the review of this training recording and presentation on the dedicated event page on EMA’s website for familiarisation with the new features.
- Updated guidance: The updated ESMP MAH User Guide and ESMP MAH Implementation Guide have been released to accommodate this new functionality. These documents provide detailed instructions on using readable IDs.

For any support you might need to navigate the latest guidance or just for assistance with your EU and UK procedure preparations, submissions, responses, etc., you can contact us on info@eureg.ie

Written by

Marian Winder

Marian Winder 1

Regulatory Guidance updates in March and April 2026

8th May 2026

Did you know that the following Regulatory Guidance was updated in March and April 2026?

HPRA (IE):

HPRA guidance issued in relation to EMA list of ingredients restricted or prohibited for use in cosmetics from 1st May 2026
CTCG Guidance and Webinar: New Article 11 Workaround for Clinical Trials:
- The Clinical Trials Coordination Group (CTCG) has published guidance for sponsors on a new workaround for Article 11 of the Clinical Trial Regulation (Regulation (EU) No 536/2014). This approach will apply from 27 April 2026.

MHRA (UK):

Apply for a licence to market a medicine
- Updated guidance on electronic submissions to the MHRA
MHRA Portal: register to submit forms
- Updated guidance to add MHRA Portal registration form
Medicines licensing: how to apply
- Updated guidance on varying, renewing and transferring ownership of a marketing authorisation were added
Clinical trials for medicines: notifiable trials.
- Updated guidance on ‘Applications that need expert advice’ to change timeline from 14 days to 28 days
- Addition of the Confirmation of Notifiable Trial Criteria form and clarification that IND refers to investigational new drug (no change note needed)
- The amended Clinical Trials Regulations took full effect on 28 April 2026
  - As such, this guidance should now be considered effective and is no longer in draft

EMA (EU wide):

As always the EMA regularly updates their website – here are some of the highlights from March and April 2026.

Medicines – Human:
- A Q&A clinic on the eAF took place on the 9^th March 2026
  - the slides from this session can be found on the EMA website.
  - The updated Variation Regulation Classification Guideline has been made available in both the interactive pdf eAF 28.0.0and in the PLM Portal web-based variation form January 2026 version.
  - Users are reminded to verify the accuracy and content of the selected scopes (including the conditions and documentation), before submitting the form to the relevant health authorities.
  - The EMA will introduce mandatory use for CAPs as of 1 September 2026.

- Updated pre-authorisation guidance
- Updated post-authorisation guidance
- Updated guidance on Mobile scanning and other technologies in the labelling and/or package leaflet of centrally authorised medicinal products
- Updated validation checklist for initial marketing authorisation applications – biologicals other than immunologicals (applicable to submissions under Regulation (EU) 2019/6)
- Updated Product Management Service (PMS) – Frequently Asked Questions (FAQs)

Medicines – Veterinary:
- Updated guidance on variations not requiring assessment (veterinary medicines)
- Updated guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations
- Updated guidance on transferring a veterinary marketing authorisation
- Updated pre-authorisation guidance under the Veterinary Medicinal Products Regulation (Regulation (EU) 2019/6); Question 2.1.5 in “Preparing the dossier” section
- Updated QRD veterinary Appendix I – Adverse event (PhV) MSs reporting details

CMDh (MRP/DCP):

Updated “Examples for acceptable and not acceptable groupings for MRP/DCP products” to reflect the possibility of accepting the grouping of related Type IA and Type IAIN variations outside the annual update
Updated “Chapter 1 – CMDh Best Practice Guide for the allocation of the Mutual Recognition variation number for Type I notifications, Type II variations, grouping and worksharing” to clarify the allocation of procedure numbers for annual update of Type IA variations
Updated “Chapter 6 – CMDh BPG for the Processing of (Super-) Grouped Applications in the Mutual Recognition Procedure” to reflect the agreement on the possibility of accepting the grouping of related Type IA and Type IAIN variations outside the annual update
Updated Questions and answers on the Paediatric Regulation to reflect update to align with the new EC guidelines on the details of the various categories of variations and operation of the procedures
Updated “Best Practice Guide for Article 45 and 46 – Paediatric Regulation – EU Worksharing Procedure” to align with the new EC guidelines on the details of the various categories of variations and operation of the procedures. Other clarification updates were included

eSubmissions:

Mandatory Use of PLM Web-Based eAF for CAPs: To continue advancing the adoption of the PLM web-based eAF, the EMA will introduce mandatory use for CAPs as of 1 September 2026.
EU eCTD v4.0 validation criteria v1.1 published. eCTD v4.0 tool vendors may now begin implementing the new rules, and the updated validation criteria will become applicable starting 15 July 2026.

For any support you might need to navigate the latest guidance or just for assistance with your EU and UK procedure preparations, submissions, responses, etc., you can contact us on info@eureg.ie

Written by

Marian Winder

Marian Winder 1

Regulatory Guidance updates in February 2026

3rd March 2026

Here are the main highlights of Regulatory Guidance updated in February 2026

HPRA (IE):

The HPRA promoted the Facilitating and Accelerating Strategic Clinical Trials (FAST-EU). FAST-EU is a pilot initiative aiming to accelerate the assessment and authorisation of clinical trials running in multiple EU/EEA countries. The pilot is currently open for submissions and is expected to run until early 2027.

MHRA (UK):

The MHRA published a few updates:

Medical devices regulations:
- Targeted consultation on the indefinite recognition of CE marked devices in Great Britain.
Addition of the latest Additional Monitoring List for Jan 2026
New information on responsibilities and reporting on nitrosamine impurities

EMA (EU wide)

As always the EMA regularly updates their website – here are some of the highlights from February

Medicines – Human:
- Updated validation checklist for Type II variations
- Concept paper on the revision of the guidelines on Good
  Manufacturing Practice for medicinal products – Annex 15
  – Qualification and Validation. Public consultation began on 09th February
- ICH M15 Guideline on general principles for model-informed drug development, document updated
- Guidance for applicants for the preparation of the ‘precise scope’ section of the variation application form, document updated
Medicines – Veterinary:
- Guideline on quality aspects of mRNA vaccines for veterinary use, Public consultation began in February
- Question and answer on the information contained within section 4.2 of the SPC on pharmacodynamic properties for pharmaceutical products
Annual fees payable to the EMA, page updated
Reflection paper on the qualification of non-mutagenic impurities
FAQ document published to address common queries and provide guidance on the European Shortages Monitoring Platform (ESMP)
List of European Union reference dates (EURD) and frequency of submission of periodic safety update reports (PSURs) excel is updated
List of contact information for the national competent authorities in the EEA page updated
Updated PRAC report templates
Guidance on Good Pharmacovigilance Practices (GVP) updated
Summary from the industry stakeholder webinar on the revised guideline on the environmental risk assessment of medicinal products for human use
The next eAF Q&A will be on the 9th of March

CMDH (MRP/DCP):

Agenda for the 24-25 Feb Meeting
Report from the CMDh meeting held on 27-28 January 2026
Q&A – Generic Applications

eSubmissions:

Updated PLM Portal eAF Release notes (version: 1.2.1.6 – Release date 16/02/2026)

For any support you might need to navigate the latest guidance or just for assistance with your procedure preparations, submissions, responses, etc., you can contact us on info@eureg.ie.

Written by Fiona Downey

Fiona Downey

Regulatory Guidance updates in January 2026

30th January 2026

Were you aware that the following Regulatory Guidance was updated in January 2026?

HPRA (IE):

Updated fee guidance document for Human medicinal products

MHRA (UK):

The MHRA have been very busy updating their website in January – here are some of the highlights

Medicines: International Recognition Procedure
- Updated dates indicating the submission deadlines for IRP Route B applications in the IRP Guidance page
Medicines: Apply for a variation to your Marketing Authorisation
- Updated to add new section on Type II variations – ‘Variations to add a new therapeutic indication’
Medicines: Statement on new review of paracetamol safety during pregnancy
- Paracetamol should be taken as directed in the patient information leaflet
Medicines: that you can export from the UK or hoard
- Updated to add: Aspirin (strength: all; pharmaceutical form: all); and Ifosfamide (strength: 1g/2g; pharmaceutical form: powder for solution for injection vials)
Medicines: get scientific advice from MHRA
- Removed info box at the top of the page as out of date
Human and Veterinary: Register of licensed manufacturing sites
- Updated to add the MS and MANSA registers for January 2026
Updates to the Orphan Register
Early Access to Medicines Scheme: Overview
- Updated scientific opinion dates for EAMS 2026
Clinical Trials: apply for authorisation in the UK
- Updated to provide link and information under ‘Combined review of an investigative medicinal product and medical device – IMP+Device’
Patients to benefit sooner as UK boosts clinical trials attractiveness with faster assessment and agile regulation
Borderline products: how to tell if your product is a medicine
- Updated to add Statistics table for May-October 2025

EMA (EU wide)

As always, the EMA regularly update their website – here are some of the highlights from January

EMA post-authorisation guidance – updated
Dates of 2026 Scientific Advice meetings and submission deadlines
Medicines: Use of Paracetamol during pregnancy unchanged in the EU
- Recent publication confirms no increased risk of autism, ADHD or intellectual disability
EMA and FDA set common principles for AI in medicine development
IRIS guide for applicants – updated
Meeting highlights from Pharmacovigilance Risk Assessment Committee (PRAC)
Meeting highlights from Committee for Veterinary Medicinal Products (CVMP)
Published the Annual report of the Good Clinical Practice (GCP) Inspectors working group 2024
Q&A about the clinical study data proof-of-concept pilot for industry – published
One Health Approach
- updated to include ‘One Health task force‘ section
Q&A clinic: New Variation classification in eAF (recording available)
3 year rolling work plan for the Quality Innovation Group (QIG)

CMDH (MRP/DCP):

Updated ‘contact points’ excel
- This excel provides names, email addresses and phone numbers for seeking advice from each member state in the EU/UK for regulatory procedures
National recommendations for requests to act as RMS – updated
Recommendation for classification of unforeseen variations according to Article 5 – corrected
ASMF workshare procedure user guidance – updated

eSubmissions:

Updated PLM Portal eAF release notes
European Shortages Monitoring Platform (ESMP)
- Expanding to include: new tools and features to better support stakeholders in preventing, managing and mitigating medicine shortages
Updated Variation Regulation Classification Guideline
- has been made available in the interactive pdf eAF v1.28.0.0 and in the PLM Portal web-based variation form January 2026 version
Go-Live announcement for EU eCTD v4.0 optional use for Centralised Procedure new MAAs

For any support you might need to navigate the latest guidance or just for assistance with your procedure preparations, submissions, responses, etc., you can contact us on info@eureg.ie.

Written by Alice D’Alton

Alice Dalton 1

Implementation of the revised variations categories – EU and UK

15th January 2026

Are you ready to implement the revised variations categories guidance?

As of today (15th January 2026) they are to be used for any variation procedure submitted in the EU and UK : EU – New Variations Guidelines in the EC’s Official Journal

Regulation (EU) 2024/1701 of 11 March 2024, amending Regulation (EC) No 1234/2008 was entered into force on 7 July 2024. It became applicable on 1 January 2025. The new categories are effective from 15th January 2026.

The changes are summarised as follows:

This guidance no longer applies to Veterinary Medicinal Products (now governed by Regulation (EU) 2019/6)
The Article 5 recommendations accumulated since 2013, for changes not foreseen in the previous version of the category guidance, have all been incorporated into the new guidance.
The scope of changes, previously designated as A, B C and D are now replaced by E (Admin), Q (Quality), C (Safety, Efficacy & PV) and M (PMF/VAMF).
The latest version of the eAF (e.g. interactive pdf eAF v1.28.0.0 or PLM Portal web-based variation form January 2026 version) must be used from 15th January onwards
Updates to most variation categories include amendments to the conditions to be met, documentation required for submission and addition of notes to clarify when the category is most suitable
Mandatory Annual Reporting requirements are added
Clarifications on Super-grouping are added
Clarifications on Work-sharing are added
Encouraged use of Post-Approval Change Management Protocol (PACMP) and Product Lifecycle Management (PLCM)

Remember:

Where a variation is considered unclassified, a detailed justification for its submission as a minor variation of Type IB (or major variation of Type II, when requested by MAH) must be included.
Where a proposed variation is not considered/classified as a minor variation of Type IB and the relevant authority/agency is of the opinion that it may have a significant impact on the quality, safety or efficacy of the medicinal product, the holder shall be informed immediately. In such cases, the holder will be asked to amend their application and to complete it in accordance with the requirements for a major variation of Type II. Once the valid revised variation application has been received, a major variation of Type II assessment procedure is initiated
Where the same variation of Type IB/Type II affects several marketing authorisations owned by the same holder, the holder must submit these variations as a single application for worksharing. If a submission has been made as one or several variations but not including all affected marketing authorisations owned by the same holder in a single application as worksharing, the holder shall amend their application.
This Annex does not deal to the classification of extensions, which are exhaustively listed in Annex I of the Variations Regulation. All changes set out in Annex I of the Variations Regulation must be considered extensions of the marketing authorisations

The EU guidance will also apply for the UK and the MHRA want MA Holders to provide also a contents page included with the submission, listing all documents included in the eCTD sequence.

If you would like to discuss any of the above and if you need support for any of your Variation applications we are ready to assist you and your team.

Feel free to contact us and we will be happy to help.

Written by Alice D’Alton

Alice Dalton 1

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

ICH M4Q(R2): The Exciting Evolution of eCTD Modules 2.3 and 3.2

Regulatory Guidance Updates in May 2026

Regulatory Guidance updates in March and April 2026

Regulatory Guidance updates in February 2026

Regulatory Guidance updates in January 2026

Implementation of the revised variations categories – EU and UK

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

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