Market Authorization of Biological Medicinal Products in EU

Definition of Biological Medicinal Products:

According to Part I Annex I of Directive 2001/83/EC, a biological medicinal product is a product that contains a biological substance. A biological substance is a substance that is produced by or extracted from a biological source and that needs a combination of physico-chemical-biological testing together with the production process and its control for its characterization and the determination of its quality.


List of Biological Medicinal Products:




Allergen products (e.g. for allergy shots and tests)




Blood or plasma derived products and their recombinant alternatives












Monoclonal Antibodies







Biotechnology derived proteins as active substances



Advanced Medicinal Therapies such as Tissue Engineering, Gene therapy, Cell therapy etc.




Regulatory Pathway for Biological Medicinal Products:


Market Authorization Procedures in EU:

Centralized Procedure

National Authorization

Mutual Recognition Procedure

Decentralized Procedure

This procedure results in a Single Market Authorization that is valid in all EU countries

Individual Application to Each Country in EU

Single Application Reviewed by One Member State for Authorization and other Member States accept the decision

Individual Application to all Concerned Member States (CMS); Simultaneous review and authorization by all CMS

This procedure is mandatory for following products:

  1. Medicines derived from biotechnology processes, such as genetic engineering;
  2. Advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines;

3.     Orphan medicinal products

4.     New active substances for which the therapeutic indication is the treatment of:

a.      Diabetes

b.     Cancer

c.      HIV/AIDs

d.     Neurodegenerative diseases

e.      Auto-immune diseases

f.       Other immune dysfunctions

g.      Viral diseases

Applicable for all products that fall outside the scope of EMA centralized procedure

Applicable for all products that fall outside the scope of EMA centralized procedure

Applicable for all products that fall outside the scope of EMA centralized procedure

This procedure can be optionally used for following products:

1.     Medicines with significant therapeutic, scientific or technical innovation

2.     In the interests of patients at community level:

a.      Medicines for pandemic

b.     Generic medicinal products of nationally authorized reference medicinal products

c.      OTC medicinal products

d.     Generic medicinal products of reference medicinal products authorized by this procedure


Overview of Contents of Clinical Trial Application (CTA):

1.     Covering Letter

2.     Application Form

a.      Module 1 – Contains information on the administration of the trial, trial site(s) with principal investigator(s), the trial design and on the investigational medicinal products (IMP).

b.     Module 2 – Represents national or local Ethics Committee application form (optional).

3.     Clinical Trial Protocol

4.     Information on Investigational Medicinal Products (IMP)

5.     Recruitment Arrangments

6.     Subject information and the informed consent procedure

7.     Suitability of the investigator and quality of the facilities

8.     Insurance and indemnity

9.     Financial Arrangements



[1]  Directive 2001/83/EC

[2]  Guidelines on Application Format and Documentation for Clinical Trial

[3]  Procedure for Market Authorization

[4]  Procedure for Market Authorization – Centralized Procedure

[5]  Presentation and Format of Dossier – Common Technical Document

[6]  Guidelines for Similar Biological Medicinal Products