European medicines regulation

2. CONTENTS
 INTRODUCTION
 HISTORY OF EMA
 MILESTONES AND ACHIEVEMENTS
 RESPONSIBILITY
 FUNCTIONS
 COMMITTEES
 DRUG APPROVAL PROCESS
 CLINICAL TRIALS IN EU
 EU CTD
 BIOSIMILARS
 NEWS AND DRUG UPDATES

3. Agency overview
FORMED : January 1st 1995
HEADQUARTERS: London
JURISDICTION: Executive director, chairperson
(official power to make legal decisions and judgements)
KEY DOCUMENT: Regulation (EC) no.726/2004
OFFICIAL WEBSITE: www.ema.europa.eu

4. Description
 It is a European Union agency
 Prior to 2004, it was known as EUROPEAN AGENCY FOR EVALUTION
OF MEDICINAL PRODUCTS (EMEA)
VISION : To explore Science, Medicines & Health.
MISSION : To safeguard and promote human and animal health.
OFFICE ADDRESS:
European Medicines Agency
30 Churchill Place
Canary Wharf
London E14 5EU
United Kingdom
Tel. +44 (0)20 3660 6000
Fax: +44 (0)20 3660 5555

6.  European medical agency was founded in 1995 , has worked
across the European Union (EU) and globally to protect public and
animal health by assessing medicines to scientific standards and
by providing partners and stakeholders with independent, science
based information on medicines.
 EMA has a 20-year track record of ensuring efficacy and safety
of human and veterinary medicines across Europe, and promoting
research and innovation in the development of medicines.
 In its first two decades, the Agency recommended the
authorisation of a total 975 human and 188 veterinary medicines.
 Today EMA’s success is based on cooperation of European
medicines regulatory network, a partnership b/w EC and EEA.

7. EMA was set up in 1995 to harmonise the work of existing national
medicine regulatory bodies.
20TH ANNIVERSARY OF EMA:-
On 2015 marked the 20th anniversary of EMA. The Agency
produced a 20th anniversary book, which captures the important
progress in regulatory science and changes in medicines regulation
in the first 20 years.
50 YEARS OF PHARMACEUTICAL LEGISLATION:-
On 2015 also marked the 50th anniversary of the introduction of
the first EU legislation on human medicines.

8. RESPONSIBILITY

9. functions
SCOPE OF OPERATION :
To Explore medicinal products
How they work?:
 The European Medicines agency(EMA) works closely to national competent
authorities in a regulated network.
 The agency also implements policies and procedures to ensure it works
independently, openly and transparently.
 Maintains the highest standards in its scientific recommendations.
Compared with other regulatory agencies :
E. M. A is parallel to FDA without centralization.
CENTRALISED MARKETING AUTHORISATION :
 European economic area (EEA)
 European free trade association (EFTA)

10. COMMITTEES
1.Committee for medicinal products for human use (CHMP).
2.Pharmacovigilance Risk Assessment Committee (PRAC).
3.Committee on Herbal Medicinal Products (CHMP).
4.Committee for Advanced Therapies (CAT).
5.Committee for medicinal products for vertinary use (CVMP)
6.Committee on orphan medicinal products (COMP).
7.Paediatric Committee (PDCO).

11. The Committee for Medicinal Products for Human Use (CHMP) is
responsible for preparing the Agency's opinions on all questions concerning
medicines for human use, in accordance with Regulation (EC) No 726/2004.
The Pharmacovigilance Risk Assessment Committee (PRAC) is responsible
for assessing and monitoring safety issues for human medicines. This includes
the detection, assessment, minimisation and communication relating to the risk
of adverse reactions, while taking the therapeutic effect of the medicine.
The Committee for Medicinal Products for Veterinary Use (CVMP) is
responsible for preparing opinions on questions concerning medicines for
veterinary use.

12. The Committee for Orphan Medicinal Products (COMP) is responsible for
reviewing applications from people or companies seeking 'orphan-medicinal-
product designation' for products they intend to develop for the diagnosis,
prevention or treatment of life-threatening or very serious conditions that affect
not more than 5 in 10,000 persons in the European Union.
The Committee on Herbal Medicinal Products (HMPC) is the committee at the
European Medicines Agency that is responsible for preparing the Agency's
opinions on herbal medicines.
The Committee for Advanced Therapies (CAT) is responsible for assessing
the quality, safety and efficacy of advanced-therapy medicinal products (ATMPs)
and following scientific developments in the field.
It was established in accordance with Regulation (EC) No 1394/2007 on
ATMPs.

13.  There are two regulatory steps to go through before a drug is approved to be
marketed in the European union.
These two steps are:-
1.Clinical trial application
2.Marketing authorization application.
 Clinical trial applications are approved at the Member State level.
(The European Union (EU) consists of 28 member states)
 Marketing authorization applications are approved at both the Member State
and centralized levels.

14. CLINICAL TRIAL APPLICATION
EU Directive EC 20/2001 (April 2001) sets out the new rules and regulations for
the approval and conduct of clinical trials in Europe.
A sponsor submits a clinical trial application to the Competent Authority in
each Member State where the trials are to be conducted.
The Competent Authority has 60 days to review and approve or reject the
application.
Application is in prescribed forms and covers the proposed clinical trial
protocol, manufacturing and quality controls on the drug and supporting data
such as,
(a) chemical, pharmaceutical and biological data,
(b) non-clinical, pharmacological and toxicological data,
(c) clinical data and previous human experience.
The supporting data are submitted in the Common Technical Document (CTD)
format.

15. MARKETING AUTHORIZATION
Following successful clinical trials, the sponsor has to apply for authorization to
market the drug in Europe.
Depending on the type of drug product and the intended market, there are. four
different types of marketing authorization applications. They are:-
1.Centralised procedure.
2. Mutual recognition procedure.
3. National authorization procedure.
4. Decentralised procedure.
Class Details
Full dossier Has to contain the complete data set – CTD Module 1-5
Generic Pure generic application
Biosimilar Generic Biotech products

16. CENTRALISED PROCEDURE:
PREPARATION OF MARKETING AUTHORIZATION APPLICATION DOSSIER
The application dossier is divided into four parts:
Part I: Summary of the dossier
(Description, overall content, reporting dates and guidelines)
Part II: Chemical/pharmaceutical/biological documentation
Part III: Toxico-Pharmaceutical documentation.
Part IV: Clinical documentation
(Clinical documentation (CD) is the creation of a digital or analog
record detailing a medical treatment, medical trial or clinical test.)
(Clinical documents must be accurate, timely and reflect specific
services provided to a patient.)

17. CENTRALISED PROCEDURE
Stepwise procedure:

18. The Mutual Recognition Procedure is stated in Council Directive 93/39/EEC.
 Once a drug is approved for marketing authorization by one Member State,
it is eligible to apply for marketing authorization in other Member States
through the mutual recognition procedure since 1998.
 The first Member State that reviews the application is called the ’Reference
Member State’.
 It notifies other states, called ‘Concerned Member States’.
 The EMA forwards its opinion to the European Commission, which makes
the final decision. Altogether, the decision process may take up to 300 days
if there is no objection, and when objections are raised it takes 600 days.
The decision of the Reference Member State is forwarded to the Concerned
Member States.

19.  This procedure is used whenever a company wants to commercialize a
product in only one EU Member State.
 The National procedure is specific to each country.
 That is, each country within the EU has its own procedures for authorizing a
marketing application for a new drug.
 Sponsors can find information regarding the requirements and procedure of
each country on the websites of the regulatory agencies.
 To obtain marketing authorization in a country, the application must be
submitted to the Competent Authority (a body with authority to act on
behalf of the member state government ) of that Member State in its own
language.

20. DECENTRALISED PROCEDURE
The objective of this procedure is to obtain marketing authorizations in several
Member States, when no marketing authorization has been granted in the
European Community.
 The applicant should send an application to the competent authorities of each of the
Member States, where there is intent to obtain a marketing authorization.
 The applicant may designate a country to act as the Reference Member State (RMS).
 The RMS will start the procedure after the application is determined to be complete by
both the RMS and all the CMS(s).
PROCESS:
 The RMS forwards a preliminary Assessment Report on the dossier to the CMS(s) and
the applicant within 70 days and entire process takes 90 days.
 RMS and CMS validates the application.

22.  All clinical trials included in applications for marketing authorisation for
human medicines in the European Economic Area must have been carried out
in accordance with the requirements set out in Annex 1 of Directive 2001/83/EC.
 clinical trials conducted outside the EEA have to comply with ethical principle
equivalent to those set out in the EEA, including adhering to international
good clinical practice and the Declaration of Helsinki.
The European Medicines Agency is responsible for coordinating inspections to
verify compliance with the principles of good manufacturing practice (GMP),
good clinical practice (GCP), good laboratory practice (GLP) and good
pharmacovigilance practice (GVP).
Sampling and testing:-
The Agency also implements a sampling and testing programme aimed at
supervising the quality of centrally authorised medicines available on the
European market.

23.  The European union Common Technical Document (EU-CTD) describes the
organisation of modules, sections and documents to be used by an Applicant
for a Marketing Authorisation for a medicinal product for human use in the
European Union.
 European union adopted CTD submission since 2003.
eCTD IN THE CENTRALISED PROCEDURE:
 In centralised procedure the EMA now only accepts submissions received in
eCTD format.
 Since January 2013 and its "Mandatory from March 2014" all eCTD
submissions must be sent using the dedicated submission channels:
eSubmission Gateway (eSG) or the related eSubmission Web Client.

24.  A biosimilar medicine is a biological medicine that is
developed to be similar to an existing biological
medicine (the ‘reference medicine).
EVALUATION OF BIOSIMILARS IN EU:-
 The main part of the evaluation is a comparison of the biosimilar
with its reference medicine to show that there are no significant
differences between them.
WHAT THEY WILL COMPARE?
 The relevant regulatory authority applies stringent criteria in their
evaluation of the studies comparing the quality, safety and
effectiveness of the two medicines.

25. NEWS UPDATES
EMA’s public hearing: Giving EU citizens a voice to help reduce the risk of
sodium valproate.
NEW MEDICINES:
 SYMTUZA- Anti-vial medicine used to treat type 1 HIV-1
contains active substance DARUNOVIR and TENOFOVIR.
 INSULIN LISPRO sanofi- which is a biosimilar medicine (highly similar to
biological medicines)
used to control blood glucose level
Contains active substance INSULIN LISPRO.

26.  www.ema.europa.eu/
 Review article by Santosh Kumar “MARKETING AUTHORIZATION OF HUMAN
MEDICINAL PRODUCTS TO EUROPEAN UNION/EUROPEAN ECONOMIC AREA.
 Life science Technical bulletin by arash ghaLamkarPour “MARKETING
AUTHORIZATION PROCEDURES IN THE EUROPEAN UNION – MAKING THE RIGHT
CHOICE”.
 EU regulatory roundup
 European regulatory science (wikipedia)