Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2013 , Vol 17 , Num 1
Drug product registration and marketing authorization procedures in EU-A perspective
Ashish Kekare2, Jagadish PC3, Manthan Janodia1, Krishnamurthy Bhat3, Swati Karande4, N Udupa1
1Manipal College of Pharmaceutical Sciences, Department of Pharmacy Management, Manipal, Karnataka, India
2Manipal University, Department of Advanced Pharmaceutical Studies, Manipal, Karnataka, India
3Manipal College of Pharmaceutical Sciences, Department of Pharmaceutical Quality Assurance, Manipal, Karnataka, India
4Bioplus Pharma, Regulatory Affairs, Bangalore, India
DOI : 10.12991/201317384


Avrupa Birliği’ne üye 27 ülkeden üçü Avrupa Ekonomik Alanı (European Economic Area, EEA) ve dördü Avrupa Serbest Ticaret Birliği’ne (European Free Trade Association, EFTA) de üyedir. EEA’da piyasada bulunmak isteyen bir firma tıbbi ürünü için pazarlama ruhsatı başvurusunda bulunmak istediğinde tüm üyeler arasında geçerli olan EC726/2004 numaralı mevzuata uymak zorundadır. Avrupa Birliği geniş bir nüfusu kapsamaktadır ve piyasada bulunan ilaçların güvenliliği ve halk sağlığına sonuçları konusunda ciddi yaklaşımlar mevcuttur. Bu makalede Avrupa Birliği’nde pazarlama ruhsatına başvuruda uygulanan prosedürdeki farklı uygulamalar tartış ılmıştır.


The primary objective of European regulation is to safeguard public health, encouraging the development of the pharmaceutical industry of the EU. Prior to marketing a medicinal product in the EU, a marketing authorization (MA) (product license) must be obtained. The company (more specifically “Marketing Authorization Holder”) responsible for placing the medicinal product on the market must be established within the EEA (Iceland, Liechtenstein, Norway and the Member States of the European Union). European regulation has established and harmonized many aspects of regulating the production, distribution, and use of medicines in the EU[1].

A major and important step was taken in 1995 by creating the European agency for the evaluation of medicinal products (European Medicines Evaluation Agency, EMA) and the establishment of a Centralized procedure, leading to a single EU wide evaluation and approval of new medicines[2].

Need for the initiation of the regulation of pharmaceuticals by the impact of the Thalidomide disaster in the early 1960s. Thalidomide is a sedative designed to prevent morning sickness in pregnant women. But result of the use of this drug lead to birth of thousands of deformed babies.

This tragedy exposed the inadequacies of safety control mechanisms. In a time where pharmaceutical scientific research progressed and international trade flows increased, the existing regulatory regimes were inadequate to face the nature of the risk involved[2].

In 1965, the first European piece of legislation in the pharmaceuticals sector, the regulation (EC) was pursuing three main lines of action:

1) It clarified what a “medicinal product” was considered to be;

2) A drug would be approved for marketing, if it shows its safety, effectiveness and therapeutic value with proper documentation;

3) Laid down a number of common rules guiding testing requirements and labeling[2-3].

After this in 1975, a new wave of legislative intervention came and regulation (EC) approved three changes:

1) It developed a set of detailed common rules to standardize the tests and trials that medicinal products were subject to in the European Community.

2) A multi-state mutual recognition procedure was established, whereby a company which had received authorization to market a certain medicine in a Member State could seek the recognition of that authorization in at least five other Member States.

3) A Committee for Proprietary Medicinal Products (CPMP), including representatives of the Commission and national authorities, was created with the objective of supervising the multi- state application process and submit an opinion on whether medicines subject to that procedure complied with the requirements laid down by Council Directive 65/65/EEC[2].

Formal procedure as per Directive 75/319/EEC marketing authorization of medicinal product was; 120 days: Examination of application, member state concerned could raise reasoned objective, 60 days: Opinion of Committee for Proprietary Medicinal Products, 30 days: Statement of member states concerned on their position.

By this procedure, 41 dossiers were filed from 1978 to 1985, which covers a total of 253 individual applications made to 5 member states or more. This is shown in Table 1.

In this as per respective country, dossiers are:

TABLE 1: Dossiers filed between 1978 to 1985.

Out of 253 applications 175 got marketing authorization and 63 are definite refusals[2,4].

In 1986 multi-state procedure was introduced by Directive 83/570/ EEC, the council reformed many important aspect of the previous procedure which has been established by Directive 75/319/EEC.

Changes made were,

1. Member states must in future take into due consideration the initial authorization, save in exceptional cases when they refer reasoned objectives to the opinion of the committee.

2. To make the procedure more attractive and effective, the minimum member states concerned has been reduced from 5 to 2, and firms have at their disposal direct access to the committee.

3. To reach a decision with full knowledge of all the aspects, the concerned member states have at their disposal a detailed description of the content of the initial authorization in the form of a “Summary of Product Characteristics” as well as critical evaluation report prepared by the original country, at least in the case of new medicines.

Result of this all change in the procedure is that, in between 1986 to Feb. 1988 the numbers of dossiers submitted were 36 which cover 198 individual national applications, which is more as compared to previous applications[4]. This is shown in Table 2 below.

TABLE 2: Dossiers filed between 1986 to 1988 after changes in procedure.

This paper was prepared with the following objectives.

• To understand Marketing Authorization procedures and types of applications.

• Selection of the process and basic requirements to get medicinal product into the EU market.

• The structure of Marketing Authorization process according to EU.

Type of Study
This was an exploratory study to understand the Drug Registration and Marketing Authorization Procedures in EU.

Data Collection
The study is based mainly on the basis of data collected from various sources like various regulatory agencies such as EMA, European Economic Council (EEC) etc. The data was also collected from available literature in journal articles published.


A medicinal product can be put in to the European market after getting the marketing authorization issued by the competent authority of member state or it is granted in accordance with Regulation (EC) No 726/2004 for entire community. Holder must follow respective regulation for development of the product and choose the correct procedure to get the marketing authorization for the medicinal product. To get the marketing authorization for medicinal product, holder must be established within the EEA.


1) What We Do. European Medicines Agency. Available from:http://www.ema.europa.eu/ema/index. jsp?curl=pages/about_us/general/general_content_ 000091.jsp&mid=WC0b01ac0580028a42#[Accessed: 3 November 2011].

2) New risks and institutional imbalances: the European Medicines Agency’s Centralized procedure for medicines authorization. Available from: http://euce.org/ eusa/2011/papers/12c_barroso.pdf [Accessed: 5 November 2011].

3) Directive 65/65/EEC. Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products. Available from: http:// www.echamp.eu/fileadmin/user_upload/Regulation/ Directive_65-65-EEC__-__Consolidated_Version.pdf [Accessed: 20 November 2011].

4) Commission of The European Communities. Report from the Commission to the Council on the activities. Available from: http://aei.pitt.edu/3854/1/3854.pdf [Accessed: 5 November 2011].

5) Marketing Authorization. Procedures for Marketing Authorization Chapter 1. Revision 3. November 2005. Available from: http://ec.europa.eu/health/files/eudralex/vol-2/a/ vol2a_chap1_2005-11_en.pdf [Accessed: 20 October 2011].

6) Centralized Procedure. Procedure for Marketing Authorization. Volume 2A. Chapter 4 –Centralized Procedure. April 2006. Available from http://ec.europa.eu/ health/files/eudralex/vol-2/a/chap4rev200604_en.pdf [Accessed: 20 October 2011].

7) Regulation (EC) No 1394/2007 Of The European Parliament And Of The Council Of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. Available from: http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2007:324:0121:0137:en:PDF [Accessed: 20 October 2011].

8) Scientific Aspects and Working Definitions For The Mandatory Scope Of The Centralized Procedure [Regulation (EC) No 726/2004 of the European parliament and of the council of 31 March 2004]. Available from: http:// www.ema.europa.eu/docs/en_GB/document_library/ Regulatory_and_procedural_guideline/2009/10/ WC500004085.pdf [Accessed: 11 October 2011].

9) Narla SK. Marketing authorization of human medicinal products to European union/European economic area. Int J Pharm Sci Rev Res 2011; 10: 1-8.

10) Mutual Recognition. Procedure for Marketing Authorization. Volume 2A. Chapter 2. Revision5. February 2007. Available from: http://www.imb.ie/images/uploaded/ documents/Chap2NTA.pdf [Accessed: 11 October 2011].

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