1

Agenda
1) EMA’s current post-authorization framework (variations) with related tools for reliance (15 min)
• Elsie Merken (Scientific Officer Procedures Office, EMA)

2) Reliance for PACs in practice (10 min)

• Asmaa Fouad (Head of Central Administration of Biological & Innovative Products & Clinical Trials at EDA, Egypt, and
representative of EDA in ICH. Advisory member of ECBS-WHO)

3) Q&A Session (15 min)

Moderator: Andrew Deavin (Senior Director Vaccines Global Regulatory Affairs Asia Pacific & China, Vaccines Europe)
Participants:
• Elsie Merken (Scientific Officer Procedures Office, EMA)
• Victoria Palmi Reig (Senior International Affairs officer, EMA)
• Alberto Gañán Jiménez (Head of Committees and Quality Assurance Department, EMA)
• Isabelle Colmagne-Poulard (Head of International Global Regulatory & Scientific Policy, Merck)
• Susanne Ausborn (Global Head International Regulatory Policy, Roche, EFPIA)
• Asmaa Fouad (Head of Central Administration of Biological & Innovative Products & Clinical Trials at EDA, Egypt, and
representative of EDA in ICH. Advisory member of ECBS-WHO)
• Marie Valentin (Team Lead, Facilitated Product Introduction, Regulation and Prequalification Department, World Health
Organisation)

4) EMA’s future post-authorization framework (variations) (15 min)

• Virginia Rojo Guerra (Head of Procedures Office, EMA)
2
 Agenda
5) EMA’s renewal framework (10 min)
• Rachel Turner (Scientific Officer Therapies for Endocrine and Cardiovascular Diseases Office, EMA)

6) Q&A Session (15 min)

Moderator: Isabelle Colmagne-Poulard (Head of International Global Regulatory & Scientific Policy, Merck, EFPIA)
Participants:
• Elsie Merken (Scientific Officer Procedures Office, EMA)
• Virginia Rojo Guerra (Head of Procedures Office, EMA)
• Rachel Turner (Scientific Officer Therapies for endocrine and cardiovascular diseases Office, EMA)
• Victoria Palmi Reig (Senior International Affairs officer, EMA)
• Martin Harvey Allchurch (Head of International Affairs, EMA)
• Alberto Gañán Jiménez (Head of Committees and Quality Assurance Department, EMA)
• Asmaa Fouad (Head of Central Administration of Biological & Innovative Products & Clinical Trials at EDA, Egypt, and
representative of EDA in ICH. Advisory member of ECBS-WHO)
• Marie Valentin (Team Lead, Facilitated Product Introduction, Regulation and Prequalification Department, World Health
Organisation)
• Andrew Deavin (Senior Director Vaccines Global Regulatory Affairs Asia Pacific & China, Vaccines Europe)
• Susanne Ausborn (Global Head International Regulatory Policy, Roche, EFPIA)

7) Final remarks (5 min)

• Martin Harvey Allchurch (Head of International Affairs, EMA)
• Susanne Ausborn (Global Head International Regulatory Policy, Roche, EFPIA)
3
EMA post-authorisation
framework
Tool to support reliance for
variations

Classified as public by the European Medicines Agency

Overview
• EU Variations Regulatory Framework
• Transparency: information published by EMA
• EMA procedures and reliance documents generated alongside
variations
• Take home messages

2 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

EU Variations Regulatory Framework

Variation Regulation
Variations Classification Procedural and Scientific
(EC) No 1234/2008,
Guideline Guidance
as amended

3 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

EU Risk based categorisation of variations

1. Changes to Active Substances

2. Changes to Strength,
Variations Pharmaceutical Form and
Route of Administration

Type IA/IAIN Type IB Type II Extension

"Do & tell" “Tell, wait and do"

“Changes requiring prior approval"

Evaluation procedure adapted to the level of risk

4 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

Reliance in the EU network required standardisation

Legislation

Application
Inspections Format (CTD)

A common and single

system based on full
transparency
enabling worksharing Scientific
Guidelines and
Procedures,
Timetables,
and reliance standards Assessment templates

5 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

Transparency: what EMA publishes and when

• Framework for transparency is embedded in EU legislation.

• EMA publishes information on human medicinal products at various
stages of their life cycle, from the early developmental stages through
our evaluation of authorisation applications, RMPs, post-authorisation
changes, safety reviews and withdrawals.
• This guidance helps stakeholders know what kind of publications to
expect on medicines undergoing evaluations and many other
regulatory procedures.
• This transparency enables many regulatory authorities to rely on
EMA’s assessment of medicines.
• A comprehensive set of documents, including European Public
Guide to information on human
Assessment Report (EPAR), is published on the medicine’s page.
medicines by EMA

6 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

Information published by the EMA

European Public Assessment Report (EPAR) includes:

information about the product

approved product information

conditions to the MA and risk management plans

scientific discussion and benefit risk assessment

(CHMP assessment report)

information on the post-authorisation procedures

7 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

Reliance documents generated alongside a
type II variation
Variation Clock stop Evaluation Clock stop CHMP CPP upon
submission Evaluation (optional) (optional) (optional) opinion request
In practice 5-12 months between valid submission to CHMP opinion

Listing of post
EPAR authorization
 procedures in EPAR

1 to 3 ≤1 month 1 to 2 1 to 2 Final assessment Full EPAR/RMP/PI***

Validation
months* unless justified months months report 2 months

CHMP opinion*** Approval**

Updated Assessment Report* or RfSI Additional RfSI (D60 + 15 Days (EC decision)
CTD dossier (Request for supplementary information) (When applicable) if no question)* 2-12 months

Existing Eudra
GMDP
certificate(s)
EMA Documents publicly available
Inspection of new site(s) with report(s), when GMP status to be assessed EMA Output to Company
Provided by Company
*Most cases are 60 days ; May be reduced to 30 days for urgent safety issues, or extended to 90 days for changes to therapeutic indication(s) or grouping
8** NotPresentation titleif EC Annexes affected): within 2 months (Art. 23.1a(a)) to 1 year after CHMP opinion (regulation 712/2012)
always issued (only
*** Not always publicly issued (only if changes/new or changes to indications or contra-indications or posology): 2 months after approval
Classified as public by the European Medicines Agency
Reliance documents generated alongside a
type IB variation
Variation Clock stop Evaluation CPP upon
submission Evaluation (optional) (optional) request
In practice 1 to 3 months between valid submission to Notification

Listing of post
 EPAR authorization
procedures in EPAR*

7 Days for
30 Days 30 Days 30 Days Notification
validation

D30 D60 D90 (EC decision)***

Updated
Notification Response to RfSI Final AR
CTD dossier 2 months to 1 year
or RfSI (When applicable) (When applicable)

Existing Eudra
Implementation
GMDP
Possible
certificate(s)

EMA Documents publicly available

EMA Output to Company

* Procedures requiring immediate Commission Decision: EPAR publication following adoption of the EC decision
Provided by Company
** Not always required (only if the Commission Decision granting the Marketing Authorisation requires amendments)
Presentation
i.e title within 2 months (for changes to indications, contra-indications, posology) to 1 year after Valid notification
EC Annexes affected:
AR = Assessment Report ; RfSI = Request for supplementary information
Classified as public by the European Medicines Agency
Reliance documents generated alongside a
type IA/IAIN variation
Variation submission EMA check CPP upon
(Do & Tell*) request
30 days between submission and Acknowledgement of Receipt

Listing of post
EPAR authorization
procedures in EPAR

Implementation 30 Days

Updated D30 (EC update)**

CTD dossier  Acknowledgement of receipt Within 1 year

Existing Eudra
GMDP
certificate(s)

EMA Documents publicly available

EMA Output to Company

Provided by Company
* Do Presentation
and Tell; Type IA: Annual Update within 12 months following implementation; Type IAIN: Immediate Notification.
title
** Not always required, only if the Commission Decision granting the Marketing Authorisation requires amendments

Classified as public by the European Medicines Agency

Type IA/IAIN Acknowledgment of Receipt

Agency reviews the notification: B.I.b.2 Change in test procedure for active substance or starting Cond. to Docum. Proce
material/ reagent/intermediate used in the manufacturing be to be d.
- Correct classification process of the active substance fulfilled supplied type

- All conditions are met a) Minor changes to an approved test procedure 1, 2, 3, 4 1, 2 IA

- Supportive documentation
Conditions
Appropriate validation studies have been performed in accordance with the relevant guidelines
1
and show that the updated test procedure is at least equivalent to the former test procedure.
There have been no changes of the total impurity limits; no new unqualified impurities are
2
detected.
The method of analysis should remain the same (e.g. a change in column length or temperature,
3
but not a different type of column or method).
The test method is not a biological/immunological/immunochemical method, or a method using a
4 biological reagent for a biological active substance. (does not include standard pharmacopoeial
microbiological methods).

Documentation
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA
volume 6B format for veterinary products, as appropriate), , including a description of the
1
analytical methodology, a summary of validation data, revised specifications for impurities (if
applicable).
Comparative validation results, or if justified comparative analysis results showing that the
2 current test and the proposed one are equivalent. This requirement is not applicable in case of an
addition of a new test procedure.

An aligned variations classification system

facilitates reliance

11 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

 EMA output documents for variations

Checked by EMA Assessed by CHMP-PRAC-CAT Rapporteur

Type IA/IAIN variations Type IB variations Type II variations

Documents Documents Documents

Outcome
documents Acknowledgement of Receipt Notification Opinion
to applicant (AoR) Assessment Report Final Assessment Report
[Commission Decision] [Commission Decision]

EPAR Publication EPAR Publication EPAR Publication

EPAR Procedural steps taken and Procedural steps taken and Procedural steps taken and
published on scientific information after scientific information after scientific information after
EMA website authorisation* authorisation* authorisation*

[Product Information] [Product Information] [Product Information]

[Risk Management plan] [Risk Management plan] [Risk Management plan]
[Public assessment report]
* EPAR, including listing of post authorization procedures, is published following finalization of procedures affecting PI or RMP
[…] published when relevant
12 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

EPAR Medicines | European Medicines Agency (EMA)

Risk Management Plan

Authorised product information

All EU languages

Authorised presentations

Changes since initial

authorisation of medicine
Procedural steps taken and
scientific information after
authorisation
Assessment report
post-authorisation procedures

The EPAR is updated when variations affect the product information or the risk management plan.
13 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

Take home messages

• The outcome generated following a variation procedure provides a

good basis for informed reliance on the work done by the Agency.

• This includes:

 Output documents generated by the Agency and shared with

the applicant

 Information published on the Agency’s website as part of

the EPAR

• Only the EPAR or Final assessment report represents the final

scientific discussion and conclusions. Other EMA assessment
reports only represent the status of the evaluation at different
timepoints.

• An aligned variations classification system facilitates reliance.

14 EMA – Tools to support reliance for variations

Classified as public by the European Medicines Agency

 Thank you

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RELIANCE PRACTICES IN THE EGYPTIAN
DRUG AUTHORITY
A STORY OF TRUST & TRANSPARENCY

Asmaa Fouad.
Head of Central Administration of Biological, Innovative
products and Clinical Trials, EDA. Member of Supreme Council
for Clinical Research Ethics oversight.
EDA, Egypt representative in ICH and vice-chair of IPRP
management committee.
Advisory member in ECBS, WHO- TAG member in LPTT,WHO.
INDEX
1 Introduction

2 Challenges faced & opportunities captured

3 Reliance Practices over the time & over the functions.

4 Post Approval Changes & Reliance through product life cycle

5 Lessons learnt from EDA journey

 INTRODUCTION

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 ABOUT EDA

January 2020
• President issue Law No. • Prime minister decree
151 of 2019 to establish 777 of 2020
the Egyptian Drug • President Issue Decree • The executive
Authority (EDA)“The number 18 of 2020 for regulations of Law No.
official drug regulatory Formulation of board of 151 of 2019.
body in Egypt” directors

August 2019 March 2020

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 EDA MOVEMENTS INTERNATIONALLY
EMPOWERING RELIANCE

2022:
EDA reached Maturity Level 3
(ML3) for Vaccines & became a
Transitional WHO Listed
Authorities (tWLA)

2024
The Egyptian Drug Authority (EDA)
attained ML3 for medicines

https://cdn.who.int/media/docs/default-source/medicines/regulatory-systems/wla/list-of-nras-operating-
at-ml3-and-ml4.pdf?sfvrsn=ee93064f_23&download=true

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 EDA MOVEMENTS INTERNATIONALLY
EMPOWERING RELIANCE

2021:
EDA Joined ICH as Observer

EDA became member in IPRP

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 EDA MOVEMENTS
INTERNATIONALLY
EMPOWERING RELIANCE

2023:

EDA become an ICH member

as 1st African and

2nd Arabic member

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 OPPORTUNITIES & CHALLENGES EDA
FACED

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 CHALLENGES EDA FACED

- Need for regulations update to include reliance in the legal

framework………..Issued

- Need for clear vision, regulatory supportive tools ( Reference

agency assessment reports, CPPs, inspection
reports…..etc.)& procedures for implementation……Done

- Regulators mind shift towards proper & good reliance

practices ( Change management)……..Improved

- Elevated backlogs & regulatory resources constraints

specially during pandemic………Controlled

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 OPPORTUNITIES EDA CAPTURED

EDA still sees more opportunities for more Reliance through:

-More harmonization of technical requirements that makes

harmonization of regulatory requirements easier.

-Continuous update of the dynamic list of reference authorities

based on justified selection criteria.

-More investment in Regulatory System Strengthening to move from

relying agency to WLA as per WHO evaluation.

-Technology as an enabler through more engagement in Pilots with

EMA

-Use of CRP/WHO soon.

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 RELIANCE PRACTICES OVER THE TIME &
OVER THE FUNCTIONS.

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 RELIANCE PRACTICES OVER THE TIME &
OVER THE FUNCTIONS

2016 2023
• Reliance on • Reliance on
the GMP the • Reliance in
inspection • Reliance on • Reliance on Lot Release
the MA assessment the
of EMA for
approval assessment Biologicals
from EMA and/or FDA of PAC
for MA • Reliance in
and/or FDA CT protocol
2015 2022
2024

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 POST-APPROVAL CHANGES & RELIANCE THROUGH
PRODUCT LIFE CYCLE

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 POST-APPROVAL CHANGES

A post-approval change to a Marketing Authorisation refers to:

Any change to the dossier status that is present in its
latest version at the Authority
Any change in the quality, safety, efficacy or in the administrative
information of a product is considered a
Post-Approval Change (PAC)

Certain major changes, such as introduction of different strength, changes in

dosage form, route of administration, and/or presentation may necessitate the
filing of a new application for marketing authorization and cannot be evaluated
as post-approval changes
© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED
 Since the regulation of changes to an
approved products is the key to ensure that
the post change products are of consistent
quality, safety and efficacy

On 17-12-2023
EDA published
“Guideline on the regulation of
Post-approval changes to a
registered Biotherapeutic
products in Egypt”

After displaying the draft guidance for public consultation

and considering the comments of different stakeholders
© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED
 REPORTING CATEGORIES OF POST-APPROVAL CHANGES

i. Quality ii. Labelling

changes changes iii. Administrative

Major quality
Safety and efficacy change
change
(i.e Scientific data Changes related to the
update) administrative as well as
Moderate quality the legal information of
change the biotherapeutic
Product labelling product.
information change
Minor quality (i.e Safety data update)
change (i.e. MAH change,
name and address of
Administrative product manufacturing facility,
Quality change with labelling information etc.).
no impact change

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 PAC SUBMISSION PATHWAYS

Normal Reliance
Notification
pathway pathway
Applicant submits required
documents as described in
Normal track “Guideline on the regulation
of Post-approval changes to
a registered Biotherapeutic
products in Egypt” and
The simultaneous receives acknowledgment
Parallel submission of the same
of Submission after 20 WDs
submission change to multiple
regulatory authorities
© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED
 RELIANCE FOR PAC

EDA extended Reliance practice to Post approval changes by

applying a verification route with shortened times for approving
post-approval changes to quality and product labels changes.

Procedures for Time line will be

handling are expected shorter than in the
to be more expedite normal track

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 RELIANCE FOR PAC..LIST OF
REFERENCE COUNTRIES.

Pathway Normal Reliance Notification

• Major and Moderate

All variation types
Quality changes.
Applicable on except Minor quality Minor quality changes
• Product labelling
changes
information changes

All imported and All imported and

Eligible Products imported from
locally manufactured locally manufactured
products references countries
biological products biological products

Timelines Longer timelines Shorter timelines 20 WD

Prior
appointment https://www.edaegypt.gov.eg/media/d30jby1q/note-to-applicant-eda-list-of-
Yes Yes No
required reference-countries_.pdf
© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED
 Normal track Reliance track
Submission Phase Submission Phase

Validation Phase Verification Phase

Quick review of the proposed scope of variation Submitted documentation is checked
and documentation and provides the applicant versus the reliance checklist to verify that the
with a validation Report mandatory documents are fulfilled

within 5 WDs within 5 WDs

Scientific review phase The MAH shall receive an e-mail showing

Detailed review of the proposed scope of the submission status
variation (Received/Not received)

within specified timelines

Complementary documents (if any) are fulfilled Complementary documents (if any) are fulfilled
and rest of the documents are verified and rest of the documents are verified

Final Decision Final Decision

Normal and Reliance pathways Timelines
Normal track
Reporting category Review Reliance track
timeline
Administrative changes 10 WDs Review
Reporting category
Quality changes timeline
Major quality changes 60 WDs Quality changes
Moderate quality changes 40 WDs Major quality changes 15 WDs
Minor/Annual report NA Moderate quality
10 WDs
changes
Labelling changes
Safety and efficacy changes 40 WDs
Labelling changes
Product labelling information changes 30 WDs
Product labelling
10 WDs
information changes
Administrative product labelling changes 10 WDs

Pack update 10 WDs

 RELIANCE FOR PAC

Assuring “sameness of product” is essential for the use of reliance

Number of PAC decisions issued through Reliance pathway

since Jan 2024
PAC category Number
Quality Changes 138

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 RELIANCE FOR PAC
Significant increase in number of PAC decisions monitored

Number of PACs decisions Number of PACs decisions

after new guideline/since begore new guideline (from
Jan. 2024 August 2022-December
2023)
951 676

For 5 quarters, an increase by 140% of work

output was observed

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 LESSONS LEARNT FROM EDA JOURNEY .

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

 LESSONS LEARNT FROM EDA JOURNEY

- Informed Reliance is a key to set the system & change the

culture.
- Harmonization is an enabler to good reliance practices.
- International cooperation & sharing best regulatory practices
are mandatory for Reliance.
- Agile & fit-for-purpose regulations are all-time enablers to good
regulatory practices.
- Always be patient-centric regulator…don’t keep them waiting!
- It is all about Trust & Transparency.

© 2025 THE EGYPTIAN DRUG AUTHORITY, ALL RIGHTS RESERVED

Changes to the EU
variations framework
WEBINAR ON RELIANCE FOR POST-AUTHORIZATION

3rd April 2025

Presented by: Virginia Rojo

Head of Procedures Office - EMA

Classified as public by the European Medicines Agency

 Changes to the Variation Regulation

• Last revision of the Variation Regulation was in 2012. Mounting pressure from the network and
stakeholders to review the variations framework (Regulation and Guidelines).

• Aim to improve the existing system by incorporating experience gained and make the lifecycle
management of medicines more:
• Efficient for regulators and MAHs
• Future proof with scientific and technological progress

• Simplify and enable an agile review of classification guideline and operational procedures

2 Revision of Variations framework

Classified as public by the European Medicines Agency

Relevant changes of the amended Variation Regulation

Efficiency gains
 Super-grouping of Type IAs when the same change(s) impacts more
than one MA
 Annual update of type IA variations: previously optional, now
mandatory with exceptions to keep some flexibility (including flexibility for
reliance).
 Worksharing procedure (same variation applicable to different MA with
no product specific assessment):

• Mandatory WS (same MAH): previously optional. Significant gains in

terms of resources and harmonisation are expected.

• Voluntary WS (different MAHs): legal recognition, pending agreement

from Competent Authorities

• WS procedure timelines no longer aligned with type II variations, but

according to highest type of variation included

3 New Variation Regulation

Classified as public by the European Medicines Agency

Relevant changes of the amended Variation Regulation

Future proofing

 End of automatic Type II for biological products based on experience acquired in

the last decade*.

 Additional regulatory tools: legislative recognition/update of design space and post

approval change management protocol (PACMP) to build on product-specific
approach*.

 Medical devices: legislative recognition of life-cycle for medicinal products combined

with a medical device*.

 Health threats: lessons learnt from pandemic

• Possibility of a fast-track procedure for annual (seasonal) update of covid
strains, if needed.
• Extension of flexibility to update vaccines to address a declared public health
emergency beyond influenza or covid.
* Provisions to be materialised with the revision of the EC Variations Guidelines
4 Revision of Variations framework

Classified as public by the European Medicines Agency

Relevant changes of the amended Variation Regulation

Agile update of the variation classification:

− Ongoing revision of the EC Variations guidelines aligned with the

amended Variation Regulation.

− Article 5 recommendation: optimisation of the process (recommendation

delivered within 60 days) and introduction of a mandatory consultation
between EMA/CMDh.

− Possibility of regular (annual) update of the guideline with publication of

an electronic version in the Commission website.

5 New Variation Regulation

Classified as public by the European Medicines Agency

 Type IA variations

Previous Regulation New Regulation (IAs implemented from Jan 2025)

IA variations can be submitted at any IA variations should be collected and submitted as 'IA annual update'
time within 12 months after between 9-12 months from the first implementation date included in the
implementation submission.
Exceptions: grouping, supergrouping, re-submission and exceptions listed
in guidance (shortages, public health emergencies, prior to an inspection or
MA transfer, when third countries require a CPP or EU authorization)

There should be no impact on reliance

IG: one or more IAs impacting Supergrouping: one or more IAs impacting several MAs from the same
several MAs from the same MAH MAH. Mix of CAPs and NAPs may be possible in the future

6 Revision of Variations framework

Classified as public by the European Medicines Agency

 Revision of Variations
Classification guideline

Classified as public by the European Medicines Agency

Revision of Classification Guideline - How did we do it?
Principles for the revision of the Variations guidelines

• All categories of variations were reviewed based on the experience acquired and the scientific and
technical progress.

• Aim to improve efficiencies ensuring the protection of public health.

• When appropriate, streamline the variation framework (e.g. decreasing, downgrading and
simplifying the various categories of variations).

• When possible, future proof the variations framework for the upcoming changes (e.g. adapt/prepare for
innovation).

• The changes proposed should be compatible with the options put forward by the Commission with
the targeted revision of the Variations Regulation.

8 Revision of Variations framework

Classified as public by the European Medicines Agency

Main proposals
Procedural part B. Quality variations C. Safety, Efficacy, PhV variations

• Operational details shifted Review of all categories: • Deletion of scopes (C.I.9, C.I.10, as
to EMA/CMDh guidance for easiest now done via Art. 57 database).
• Downgrade certain scopes when
updates in the future.
scientifically justified (risk/based approach). • C.I.3 expanded to include
• Change the current code system implementation of PRAC signals and
• Removed conditions for biological joint recommendations of EU
(numbering) to facilitate the
medicinal products, in certain authorities.
implementation and the transitional
circumstances allowing Type IA variations.
period
• New scope for submission of results of
• Implementation of PACMP as Type IB or assessments carried out on target
• Implementation of new/updated
Type IA also for BIO. patient groups.
procedural tools from the amended
Variation Regulation • New section on In-house reference
materials.
D. PMF
A. Administrative variations • New scopes for Medical devices (co-
• Reduction/simplification list from packed, integral, referenced) in line with • Reduction/simplification list from
8 to 5 scopes. 23 to 16 scopes.
MDR. Wording has been kept
general, focusing on impact and risk. To be
complemented with EMA/CMDh Q&A.

9 Revision of Variations framework

Classified as public by the European Medicines Agency

Implementation
• Revision of the EC Variations Guidelines ongoing. Publication by the Commission is expected
in Q2 2025.

• A transitional period will be foreseen between the publication and the entry into force to allow
companies and regulators enough time to prepare. Until the updated version becomes
applicable the current classification applies.

• Implementation work will be needed: EMA will publish specific implementation guidance
and will update references to new Variations guideline of existing regulatory and scientific
guidance. There will be changes in systems due to new scopes, different numbering.

• Public webinar information session on the amended Variations Guidelines will be organized
in due time.

10 Revision of Variations framework

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 Thank you

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EMA post-authorisation
framework
5- year renewal

Classified as public by the European Medicines Agency

Overview

1. Legal Framework
2. Key principles of the renewal procedure
3. Renewal submission content
4. Addendum to the quality overall summary
5. Addendum to clinical Overview
6. Reliance documents generated
7. Take home messages

2 5-year renewal

Classified as public by the European Medicines Agency

 1. Legal Framework – 5-yr renewal

• In accordance with Article 14(1) of Regulation (EC) No.

726/2004, a marketing authorisation (MA) is valid for
five years
• In accordance with Article 14(3) of Regulation (EC) No.
726/2004, once renewed, an MA shall be valid for
an unlimited period, unless there are PhV grounds
justifying one additional renewal.
• Typically, a product will be renewed once in the product
life cycle for an indefinite period

5-year renewal

Classified as public by the European Medicines Agency

 2. Key principles of the renewal procedure

• The renewal assessment is based on a general re-evaluation of the

benefit/risk (B/R) balance of the product
• MAH have an obligation to update the MA throughout the life-cycle of the product
as data emerge
• Renewals are not a substitute for submission of safety or efficacy data as they
become available (type I/II variations, PSUR* or other relevant procedures must
be submitted as applicable)
• Renewal applications are not an opportunity to update Module 3; Quality changes
must be submitted by the appropriate variation as they occur

*Periodic safety update reports (PSURs) | European Medicines Agency (EMA)

4 5-year renewal

Classified as public by the European Medicines Agency

3. Renewal submission content
5- year renewal*

Module 1 • Application form

• PI
• RMP (as applicable)
• A statement, or certificate of GMP
compliance

Module 2 • Addendum to quality overall

summary (expert declaration)
• Addendum to non-clinical
overview (expert declaration)
• Addendum to Clinical Overview
(PSUR structure + expert
declaration)

Module 3-5 • Not applicable

*Full submission requirements:

Renewal and annual re-assessment of marketing
authorisation | European Medicines Agency (EMA)

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 4. Addendum to the quality overall summary

• No updating of Module 3 quality data at renewal. The MAH has an obligation to keep it
updated on an on-going basis throughout the lifecycle of the product
• Declaration of compliance with Article 16(1) of Regulation (EC) No 726/2004 (the MAH has
considered technical and scientific progress on the manufacturing and control methods)
• Confirmation that all changes relating to the quality of the product have been made following
applications for variations and that the product conforms to current CHMP Quality guidelines
• Currently authorised specifications for the active substance and the finished product (with
date of latest approval and procedure number)
• Qualitative and quantitative composition in terms of the active substance(s) and the
excipient(s)(with date of latest approval and procedure number)

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5. Addendum to clinical Overview
• A discussion on the current benefit-risk balance for the product

• Based on data previously included in the PSUR and safety/efficacy data accumulated
since the granting of the MA or the last renewal, making reference to relevant new
information in the public domain

• Clinical statements* confirm that the product information is up to date, and

authorities have been kept informed of any additional data that could impact on the
B/R and the product can be renewed

*Clinical Expert Statement (confirmatory statements – as reflected in Annex II of the Guideline on the processing of renewals
in the centralised procedure)

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 6. Reliance documents generated alongside a 5-year renewal

Renewal Clock stop Evaluation CHMP EC decision CPP upon

submission* Evaluation (exceptional ) (optional) opinion request
In practice 3- 5 months between valid submission to CHMP opinion

Listing of post
 authorization
procedures in EPAR

Full EPAR***
≤1 month 1 month by Final assessment
Validation 3 months** /RMP/PI
by default default report
2 months​
CTD Approval
updated dossier
Assessment Report* or RfSI CHMP opinion
(Request for supplementary information)
(EC decision)
(D90 + 15 Days
sections if no question)* 2 months

Existing Eudra
GMDP
certificate(s)

EMA Documents publicly available

EMA Output to Company
Provided by Company

* At least 9 months prior to expiry **90 days as standard ; *** Full EPAR not routinely published (only if major public health interest) Annexes and RMP published if affected : 2 months after approval
RfSI = Request for Supplementary Information (Q&As)

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Take home messages

The 5-year renewal typically takes place once during the

lifecycle of a product

The scope is a B/R assessment; in practice the renewal is

an administrative exercise as the MAH has the obligation
to update the MA as data emerge

Published draft new pharmaceutical legislation mentions the

removal of the renewal concept

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 Thank you for
your attention

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 Thank you

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Back up slides

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 Guidance documents
◦ Guideline on the processing of renewals in the centralised procedure
Q&A at the EMA website :
– Renewals of marketing authorisations
Renewal and annual re-assessment of marketing authorisation | European Medicines Agency (EMA)

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