EU Regulatory System

EMEA Biologics

The European Commission (formally the Commission of the European Communities) is the executive branch of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union’s treaties and the general day-to-day running of the Union. The European System is based on the cooperation between the National Competent Authorities of the member states and the EMA (European Medicines Agency).

European Medicines Agency, EMA

  • The EMA is headed by the Executive Director and has a secretariat of about 897 staff members in 2019. The Management Board is the supervisory body of the EMA, responsible, in particular, for budgetary matters.
  • Responsible in EU for coordinating:
    1. Scientific resources provided by Member States for the evaluation, maintenance and pharmacovigilance of medicinal products.
    2. The Court of Justice of the European Communities exercises jurisdiction over the EMA for the application of Community Law.

The European Pharmaceutical Regulatory System is based on complementary procedure for the registration of medicinal products:

  1. Centralized Procedure: mandatory for biotech-derived medicinal products and optional for other innovative products. This results in a single marketing authorization valid throughout the EU.
  2. Mutual Recognition Procedure: The main route for non-biotech products. Establish a MA in one member state applies for other member states to recognize.
  3. National Procedure: used to authorize medicinal products for local use only

EU Regulatory Process

  • National authorities / experts – assessment
  • CHMP provided / adopts scientific opinion
    (CHMP composed of Rapporteurs – representing National Authorities)
  • European Commission – legislative decision
  • Centralised Authorisation – valid for all (27) Member States (~512 million people).


Europe’s Pharmaceutical Legislation

  • 1965: Dir 65/65/EEC : Safeguard public health after Thalidamide; a highly sophisticated system of legal provisions dealing with medicinal products.
  • 1975: Dir 75/318/EEC: Establish Laws in Member States relating to Analytical, pharmacotoxicology, and clinical standards (quality, safety, and efficacy)
  • 1975: Dir 75/319/EEC: Established CPMP to ensure companies comply with former directive and introduce concept of mutual recognition [established as a scientific review committee]
  • 1987: Dir 87/ 22 EEC: Requirements for approval of “High Technology” Medicinal Products particularly those derived from Biotechnology
  • 1983: introduction of the mutual recognition process in 1983 (established as anamendment to directive 75/319)(1), made it possible for a single national review for most pharmaceutical/medicinal products to be used as the basis for marketing authorizations in all EU countries.
  • 1991: Dir 91/356/EEC: Principles of GMP’s for human products
  • 1993: 3 Directives and a regulation together form the legal basis for the EMEA system
    Regulation (EEC) No 2309/93.
    The centralized procedures for authorizing biotechnology -derived and high technology Medicines is laid down in Council Regulation (EEC) No 2309/936 and Directive 93/41/EEC.
  • 1995: Council Regulation EEC 2309/93 ; Creation of EMEA and unification of regulatory process (creation of centralized procedure)
  • The current relevant legislation is given in Directive 2001/83/EC relating to medicinal products for human use, amended by Directives 2002/98/EC, 2003/63/EC, 2004/24/EC and 2004/27/EC.

Regulatory Processes

EMA’s Regulatory Pathway

  • The application is submitted directly to the EMA in Amsterdam.
  • At the conclusion of the Scientific Evaluation (210 days) at the Agency, the opinion of the Scientific Committee is transmitted to the Commission for single Marketing Authorization applying to the entire EU (all member states).
    EMEA Chart
  • 2001, the European Parliament and the Council adopted Directive 2001/83/EC on the Community Code relating to medicinal products for human use. The so-called “Community Code Directive” combined in one legal act nearly all aspects of European law on medicinal products.
  • The European Community revised two legislative acts: Directive 2001/83/EC on products subject to national authorisation and mutual recognition was amended by new Directive 2004/27/EC (“Revised Community Code Directive”) and the former Regulation 2309/93/EEC of 22 July 1993 on centrally authorised product was replaced by Regulation 726/2004/EC (“Revised Community Procedures Regulation”).
  • In addition several other laws were issued, such as Directive 2002/98/EC (re human blood) and Directive 2003/63/EC (re dossier harmonization) as well as Commission Regulations (EC) 1084/2004 and (EC) 1085/2003 (re variations) and directives dealing with human tissues and herbal medicinal products.
  • Regulation (EU) 2017/745 was enacted into law on May 25, 2017, replacing the EU’s Medical Device Directive (93/42EEC) and the EU’s Directive on active implantable medical devices (90/385/EEC). Per Article 117 of the new regulation, medicinal products with an integral medical device are subject to new requirements. Manufacturers and developers submitting drug–device combination (DDC) products for market approval on or after May 26, 2020, must comply with the new regulations.

EU Submission Requirements

ClinicalClinical Trial Authorisation (CTA) DIRECTIVE 2001/20/EC (1)
CommercialAuthorizationMarketing Authorization Application in CTD Format:Directive 2001/83/EC:• Article 8(3) – Full application• Article 10 – Generic, hybrid or similar biological application• Article 10a – Well-established use application• Article 10b – Fixed combination application• Article 10c – Informed consent application
Post ApprovalVariations (2)

(1) The Directive 2001/20/EC, the Directive, should be read in conjunction with this detailed guidance, Commission Directive 2005/28/EC2

(2) Variations