Medicinal products are highly regulated in the European Union (EU) and are subject to a separate, complicated system of approvals that governs how, when, where, and in what form such products will be allowed to be sold within the borders of the EU. Pharmaceutical regulatory systems in the EU comprise a decentralized body called the European Medicines Agency (EMA), Heads of Medicines Agencies (HMA), National Competent Authorities (NCAs) and European Directorate for the Quality of Medicines (EDQM). and collection of rules and regulations governing medicinal products in the EU is Eudralex. The European Medicines Evaluation Agency (EMEA) was established in London, in the year 1995, to coordinate the European Union (EU) member states for evaluating and controlling the medicinal products for both human and veterinary use The European medicines regulatory system is based on a network of around 50 regulatory authorities from the 31 EEA countries (28 EU Member States plus Iceland, Liechtenstein and Norway) EMA is responsible for the scientific evaluation, essentially of innovative and high-technology medicines developed by pharmaceutical companies for use in the EU. EMA has various committees for various categories of medicinal products Committee for Medicinal Products for Human Use (CHMP) Pharmacovigilance Risk Assessment Committee (PRAC) Committee for Medicinal Products for Veterinary Use (CMVP) Committee for Orphan Medicinal Products (COMP) Committee on Herbal Medicinal Products (HMPC) Committee for Advanced Therapies (CAT) Paediatric Committee (PDCO) For a medicinal product to seek market authorization in Europe, the manufacturer or sponsor shall choose a pathway from four different pathways based upon the type of medicinal substance, and requirements such as a number of countries chosen for marketing, timeline, etc.

1. Content and Approval Process of IMPD and
Marketing Authorization procedure in EU
Presented by: Gowthami A H
Date:02/02/2024
Department of Pharmaceutical Regulatory Affairs
Regulatory Aspects of Drugs and Cosmetics

2. CONTENTS
European medicine Agency- Overview
IMPD – Introduction
Content and Approval procedure of IMPD
Marketing authorization procedures in EU
Conclusion

3. EMA – Overview
The European Medicines Agency (EMA) is a decentralised agency of the European
Union (EU). It is responsible for the scientific evaluation, supervision and safety
monitoring of medicines.
EMA protects public and animal health in EU Member States, as well as the
countries of the European Economic Area, by ensuring that all medicines available
on the EU market are safe, effective and of high quality.
1

4. European Economic Area (EEA)
EEA includes 27 EU member states and
the 3 European Free Trade Association
states (EFTA) (Iceland, Liechtenstein
and Norway). Hence, European Economic
Area constitutes total 30 countries.
EFTA
EU member states
2

5. EEA
3
EFTA States

6. Drug approval Applications in Europe
 All clinical trials,
including phase 1 trials must
first be registered in European
EudraCT database after which
the clinical trial application
(CTA) is scrutinised by a
Competent Health Authority
and an Ethics Committee
Clinical trial
application
MAA provides comprehensive
information about a drug,
enabling regulatory agencies to
assess Quality, Safety and
Efficacy, and evaluate the
ability of the future MAH to
ensure and monitor a
sustainable benefit/risk ratio.
Marketing
authorization
application
4

7. IMPD
 The Investigational Medicinal Product Dossier
(IMPD) is a document containing information about
an Investigational medicinal product to be marketed
in the EU.
 IMPD includes detailed information essential for
regulatory authorities to evaluate the safety, quality,
and efficacy of the investigational product.
5

8. Objectives
 Since clinical trials will often be designed as multi-
center studies, potentially involving different member
states, it is the aim of this guideline to define
harmonized requirements of the documentation to be
submitted throughout the European community.
 Administrative provisions of the member states relating
to the implementation of good clinical practice (GCP)
in the conduct of clinical trials on medicinal products
for human use.
6

9. (i) Quality, Manufacture and Control of the IMP
(ii) Non-clinical studies conducted with the IMP
(iii) Clinical use of the IMP
(iv) Overall risk / benefit assessment of the IMP in
the proposed trial.
7
Sections of IMPD

10. Full IMPD Simplified IMPD
When applying for a clinical trial authorization, a
full IMPD is required when little or no
information about IMP has been previously
submitted to competent authorities, when it is not
possible to cross refer to data submitted by another
sponsor and/or when there is no MA in the
community.
A simplified IMPD may be submitted if
information has been assessed previously as
apart of a marketing authorization in any MA or
clinical trial to that competent authority. This
IMPD will also be sufficient for studies of dosing
regimens where the sponsor can demonstrate that
information justifies the safety of new dosing
regimen.
Types of IMPD
8

11. Approval process
IMPD
Ethical committee National agency
Approval notification
Clinical trial
60 days of reviewing
60 days of reviewing
9

12. Marketing Authorization Procedures in EU
Medicinal products are highly regulated in the
European Union (EU) and are subject to a separate,
complicated system of approvals that governs how,
when, where, and in what form such products will be
allowed to be sold within the borders of the EU.
10

13. Important terms
• Process of review and providing the licence to the
applicant.
Marketing authorization(MA)
• Applicant submit dossier to the authority in Europe
is called marketing authorization application
Marketing authorization
application(MAA)
• Holder of approved application
Marketing authorization
holder(MAH)
11

14. Cont.
• Committee for medicinal products for Human use.
• It is one among 7 EMA committes.
CHMP
• One of the members of committee or working
party who leads the evaluation of an application
Rapporteur
• Concerned member state
• Reference member state
CMC and RMC
12

15. EU Marketing Authorization Procedures
Centralized
Procedure
Decentralized
Procedure
Mutual
Recognition
procedure
National
Procedure
All
EU Member
State
One or more
EU Member
State
One or more
EU Member
State
Only one
EU Member
State
13

16. National Decentralised Centralised
14

17.  A single marketing authorization allows the sponsor
to market the medicine and make it available to
patients and healthcare professionals throughout
Europe.
 Results in a single authorization valid in EU, Norway,
Iceland and Liechtenstein.
 Application evaluated by an assigned Rapporteur.
 Timeline: EMA opinion issued within 210 days, and
submitted to Commission for final approval.
Centralized procedure
15
Committee for Medicinal Products
for Human Use

18. Genetic
engineering
Cancer HIV/AIDS Diabetes
Neurodegenerative
disorders
Autoimmune
diseases
Orphan medicines
16

19. CP Eligibility
request (-18
to -7 months)
Letter of
intent (-7
months)
MAA
Submission
Validation
Rapporteur
and Co-
Rapporteur
appointment
(-6 months
EMA
17

20. Clock starts Day 0
Rapporteur issue Draft
assessment report to
applicant and to CHMP
Members – Day 80
CHMP members send
their assessment to
Rapporteurs
Consolidated list of
questions sent to applicant-
Day 120
Clock Stops -1
Clock Re starts Day 121
Rapporteur issue Draft
assessment report to
applicant and to CHMP
Members – Day 150
CHMP members send
their assessment to
Rapporteurs Day 180
Consolidated list of
questions sent to applicant-
Day 180
Clock Stops - 2
Clock Re starts Day 181
Adoption of CHMP
Opinion – Day 210
Submission of product
information translations
Day 215
Final EC decision Day 277
End of procedure
18

21.  The mutual recognition procedure allows applicants
to obtain a marketing authorization in the concerned
member states(CMS) other than the reference
member state(RMS), where the drug is previously
approved.
 Applicant submits identical dossier to all member
states in which they want marketing authorization,
including required information.
Mutual recognition procedure (MRP)
19
RMS
Applicant
CMS
CMS
CMS
CMS

22.  As soon as one member state decides to evaluate the medicinal product at
which point it becomes the (CMS), to whom application have also been
submitted.
 RMS issue a report to other states on its own findings.
 Generic industry is the major user of this type of drug approval procedure.
 Assessment time: 90 days + 30 days
Cont.
20

23. Submission to RMS
Assessment report
CMS starts the procedure
Day 0
CMS comments Day 50
Applicants response
Day 60
CMS comments Day 75
21
Timeline is not
defined for MRP
Final CMS position Day 85
Close of procedure Day 90
CMS issue the National
Licenses ( STD approval
times – 30 days

24.  Using this procedure, companies may apply for authorization simultaneously in
more than one EU country for products that have not yet been authorised in any
EU country and essentially do not fall within the centralized procedure’s essential
drugs list.
 Based on the assessment report which is prepared by the RMS & any comments
made by the CMS, marketing authorization should be granted in accordance
with the decision taken by the RMS & CMS in this decentralized procedure.
 Generally used for those products that has not yet received any authorisation in
an EU country.
 Time: 210 days.
Decentralised procedure (DP)
22

25. RMS starts the procedure
RMS forward PAR and
draft to CMSs Day 70
CMS sends their
comments to RMS Day
100
CMRMS forwards PAR
with CMS comments to
Applicant Day 105
Applicant submit
responses : RMS
restarts the procedure
Day 106
RMS updates PAR to
prepare DAR and
circulates to CMSs day
120
If consensus is reached,
the procedures can be
closed and proceed to
national 30 day phase
Day 120
Start of Assessment II
End of assessment I (120
days)
RMS circulates DAR
Day 120 (Day 0)
Additional CMS
comments on DAR to
the applicants and
applicants response Day
150-160 ( Day 25-35)
RMS and CMS reach
consensus and Final
decision on Approval
Day 210 (Day 90)
23

26.  The Nationalized procedure is one which allows applicants to obtain a
marketing authorization in one member state only.
 In order to obtain a national marketing authorization, an application must
be submitted to the competent authority of the Member State.
 New active substances which are not mandatory under Centralized
procedure can obtain marketing authorization under this procedure.
 Timeline for this procedure is 210 Days.
National procedure
24

27. Applicant submits dossier
Validation
Phase - I
Applicant response
document
Phase- II
National committee board
Marketing authorization
Scientific advice
Pre-submission
Pre-submission meeting
for the MRP
25

28. Regulatory pathway Regulatory
body/Organization
involved
Timelines Authorization valid
CP CHMP/EC 210 days + 67 days for EC
Decision
One approval – all EU
member states = 3 EFTA
states
DP CMdh coordinates,
RMS + CMS
120 Days or 210 days +
National step
Parellel approval in more
than one country
MRP CMdh coordinates,
RMS + CMS
National approval + 90
days
First national approval +
added countries
NP National competent
Authority
Country specific Only one EU member
state
26

29. Mandatory CR Scope
Products can only authorized by centralized procedure.
Medicines containing a new active substance to treat HIV,AIDS, cancer, diabetes, neurodegenerative
diseases, auto-immune and other immune disfunction.
Medicine derived from biotechnology processes, advanced –therapy medicines
Orphan medicines
Optional CP Scope
Applicant can choose either CP/MRP/DCP/NP.
Containing new active substances for other than those stated in Mandatory CP Scope.
Outside of any CP Scope
Products excluded from centralized procedure.
Most generic medicines and
Medicines available without a prescription.
Choice of Authorization Route
27

30. US vs Europe
28
US Europe
Regulatory Agency USFDA EMA
Applications IND
NDA
ANDA
BLA
CTA-IMPD
MAA
Generic application
Registration process One registration process  Centralized
Procedure (CP)
 Decentralized
Procedure (DCP)
 Mutual Recognition
Procedure (MRP)
 National procedure

31. The Investigational Medicinal Product Dossier (IMPD) is a central piece of
Investigational Medicinal Product (IMP) related documents required for approval of
clinical trials by the competent authorities in the EU. An IMPD is required for IMPs to be
used in a clinical study, regardless of whether it is the test product itself, a reference
product already authorised or a placebo.
The European Medicines Agency (EMA) is responsible for the scientific evaluation of
centralised Marketing authorisation applications (MAA). Once granted by the
European Commission, the centralised marketing authorisation is valid in all European
Union (EU) Member States, Iceland, Norway and Liechtenstein.
Conclusion
29

32. References
1. Investigational Medicinal Product Dossier (IMPD) [Internet] Available from:
https://english.ccmo.nl/investigators/clinical-trials-with-medicinal-products-
ctr/preparation-ctr/research-dossier-part-i/g-investigational-medicinal-product-dossier-
impd (accessed on 20-01-2024)
2. What is IMPD? [Internet] Available from: https://www.freyrsolutions.com/what-is-
an-investigational-medicinal-product-dossier-impd (accessed on 20-01-2024)
3. Charyulu R N, Jose J. Pharmaceutical regulatory science, Nirali Prakashan, 1st edition
– 2021: 2.10 -13

33. 4. Marketing authorization [Internet] Available from:
https://www.ema.europa.eu/en/human-regulatory-overview/marketing-
authorisation (accessed on 28-01-2024)
5. Obtaining an EU marketing authorisation, step-by-step [Internet] Available from:
https://www.ema.europa.eu/en/human-regulatory-overview/marketing-
authorisation/obtaining-eu-marketing-authorisation-step-step (accessed on 28-01-
2024)
6. Marketing Authorization Procedure For Pharmaceuticals In Europe [Internet]
Available from: https://credevo.com/articles/2019/11/30/marketing-authorization-
procedure-for-pharmaceuticals-in-europe/ (accessed on 28-01-2024)

34. 7. van Gerven J, Cohen A. Integrating data from the Investigational Medicinal Product
Dossier/investigator's brochure. A new tool for translational integration of preclinical
effects. Br J Clin Pharmacol. 2018 Jul;84(7):1457-1466.
8. Garsen, M., Steenhof, M. & Zwiers, A. A Decade of Marketing Authorization
Applications of Anticancer Drugs in the European Union: An Analysis of Procedural
Timelines. Ther Innov Regul Sci 55, 633–642 (2021).
9. Muhaned Al-Hindawi, Chapter 3 - Marketing authorization and licensing of
medicinal products in EU: Regulatory aspects,Drug Delivery Trends, Elsevier,2020,
Pages 45-75.