The European Union has established a centralized system for regulating and approving pharmaceutical drugs. There are three main approval routes: the centralized route administered by the European Medicines Agency, the mutual recognition procedure, and the decentralized procedure. Stringent regulations were implemented following drug safety disasters to protect public health and ensure safe, effective medicines.

1. Prepared by:-
Shivam kumar
M.Pharm Ist sem

2. The Europe Union
 A political union also called as Europe union formed in 1993 for purpose of achieving political and
economic integration.
 The EU includes 28 members states located in Europe.
 The EU total population is about 500 millions people.
The EU operates through a system of:
I. Supranational independent institution.
2. Intergovernmental negotiated decisions by its member of the states .
 It is legal entity and can negotiate international agreement on behalf of its member states.
 In EU there are two regulatory steps by which a drug is approved in market
1. clinical trials application [approved by both member state level].
2. Marketting authorisation [ approved by both member state and centralised level]

3.  Pharmaceutical industry is most regulated of all the industries. Regulation are put in order to
develop the most efficient and safe pharmaceutical products. It takes more than 8 to 15 years
to develop a new drug products and costs more than $800 million.
 When did this regulation came?
 During the 20th century, there were no law’s and regulation to protect public from the
unfavorable effects of the drugs.
 Misfortune, disaster and tragedy had triggered most of the advances in drug regulation. There
are some examples of disaster which leads to the formation of regulation in the industry.
*Thalidomide tragedy (1962)
*Elixir sulphanilamide (1937) {taste of death}
Regulation in the Industry

4. The Role of EMA
 EMA was established in 1995 to ensure the best use of scientific resources across Europe for
the evaluation, supervision and pharmacovigilance of medicines
 EMA is responsible for the scientific evaluation, primarily of innovative and high-technology
medicines developed by pharmaceutical companies for use in the EU.
 Experts participate in the work of EMA as members of its scientific committees, working
parties, scientific advisory groups
 The experts are chosen on the basis of their scientific expertise and many of them are made
available to EMA by the NCAs in Member States.
 Increasingly, patients and healthcare professionals are involved in the work of the Agency
including in the evaluation of medicines.

5. Registration in Europe Post Nov. 2005:
 Three European Systems
Centralized Procedure (CP)
(via EMA)
Mutual recognition
procedure
(MRP)
Decentralized procedure
(DCP)

6. Marketing Authorization
To protect public health and ensure the availability
of high quality, safe and effective medicines for
European citizens, all medicines must be authorized
before they can be placed on the market in the EU.
The European system offers different routes for such
an authorization.

7.  The centralized procedure : allows the marketing of a medicine on the basis of a
single EU- wide assessment and marketing authorization which is valid throughout the
EU.
 Pharmaceutical companies submit a single authorization application to EMA.
 The Agency’s committee for medicinal products for human use (CHMP) or committee
for medicinal products for veterinary use (CVMP) then carries out a scientific
assessment of the application and gives a recommendation to the European
commission on whether or not to grant a marketing authorization.
Drug approval in Europe Union
Centralized procedure:

8.  Once granted by the European commission, the centralized marketing authorization is
valid in all EU member states. The use of the centrally authorized procedure is
compulsory for most innovative medicines, including medicines for rare diseases.
 Rules and Requirements applicable to pharmaceuticals in the EU are the same,
irrespective of the authorization route for a medicine.
 A European public Assessment report, (EPAR), is published for every human or
veterinary medicine that has been granted for refused a marketing authorization
following an assessment by EMA.
 Drug approval in Europe Union Centralized process is compulsory for:
• Those medicines which are derived from any biotechnology processes, such as genetic
engineering
• Those medicines which are intended for the treatment of Cancer, HIV/AIDS, diabetes,
neurodegenerative disorders or autoimmune diseases and other immune dysfunctions.
• Medicines officially designated 'Orphan medicines' (medicines used for rare diseases).

9. Drug approval in Europe
Union Mutual Recognition
Procedure:
Mutual-recognition procedure where companies that have a medicine
authorised in one EU Member States can apply for this authorisation to be
recognised in other EU countries. This process allows Member States to rely on
each other’s scientific assessments. 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.

10. • Applicant submits identical dossier to all EU member states in which they want
marketing authorization, including required information.
• As soon as one Member State decides to evaluate the medicinal product (at which point
it becomes the "RMS"), it notifies this decision to other Member States (which then
become the "CMS"), to whom applications have also been submitted.
• RMS issues a report to other states on its own findings
• Generic industry is the major user of this type of drug approval procedure.
• This process may consume a time period of 390 days.

11. Drug approval in Europe Union
Decentralized procedure
The decentralised procedure where companies can apply for the
simultaneous authorisation of a medicine in more than one EU Member State
if it has not yet been authorised in any EU country and does not fall within
the scope of the centralised procedure;

12. Using this procedure, companies may apply for authorization simultaneously in more
than one EU country for products that have not yet been authorized 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.

13. Drug approval in Europe Union
Nationalized Procedure
• 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.

14. DCP FLOW CHART
Applicant submits application to the RMS & CMS
RMS & CMS validates the application
RMS distributes the preliminary assessment report to the CMS
RMS sends preliminary assessment report & all comments of the CMS
to the applicant

15. Clock stops, applicant responds, clock runs
RMS sends drafts assessment report to the CMS & applicant
CMS approve the assessment report
Marketing Authorization in RMS & each of the CMS

16. MRP FLOW CHART
Applicant submits application to the RMS & CMS
RMS validates the application
RMS distributes assessment report to the CMS

17. CMS approves the assessment report
CMS Validates the application
Marketing authorization in each of the CMS

18. The European Commission can also take action concerning other aspects of
medicine regulation:
• Right of initiative – it can propose new or amended legislation for the
pharmaceutical sector;
• Implementation – it can adopt implementing measures as well as oversee
the correct application of EU law on pharmaceuticals;
• Global outreach – it ensures appropriate collaboration with relevant
international partners and promotes the EU regulatory system globally.

19. EMA’s scientific committees
The EMA has seven scientific committees that carry out its
scientific assessments:
• 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)

20. NATIONAL COMPETENT AUTHORITIES
 The national competent authorities (NCAs), responsible for the regulation of human
and veterinary medicines in the EU, coordinate their work in a forum called Heads
of medicines Agencies (HMA).
 The heads of the NCAs work closely with EMA and the European Commission to
maximize cooperation and ensure the European medicines regulatory network
functions efficiently.
 The HMA meets four times per year to address key strategic issues for the network,
such as the exchange of information, sharing of best practices, and to streamline
mutual recognition and decentralized procedures.

21. GUIDELINE AND SCIENTIFIC ADVICE
 EMA prepares scientific guidelines in cooperation with experts from its scientific
committees and working groups.
 These guidelines reflect the latest thinking on developments in biomedical science.
 This is an important tool to help develop and make available high quality, effective and
safe medicines, for the benefit of patients.
 Scientific advice can also be given by NCAs.

22. SAFETY AND MONITORING OF MEDICINES
 The European regulatory system for medicines monitors the safety of all medicines that
are available on the European market throughout their life span.
 EMA has a committee dedicated to the safety of medicines for human use – the
Pharmacovigilance Risk Assessment committee, or PRAC.
 If there is a safety issue with a medicines that is authorized in more than one member
state, the same regulatory action is taken across the EU and patients and healthcare
professionals in all member states are provided with the same guidance.

23. CLINICAL TRIALS
 The authorization and oversight of a clinical trial is the responsibility of the member state in
which the trial is taking place. The European clinical trials database (Eudra CT) tracks which
clinical trials have been authorized in the EU.
 It is used by NCAs and clinical-trial sponsors to enter information protocols and results of
clinical trials.
 A subset of this information is made publicly available by EMA via the EU clinical trials
register.