EU guidelines for biosimilars

Last update: 8 January 2016

The regulatory body for approval of medicines in the European Union (EU) is the European Medicines Agency (EMA). The agency is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the EU.

All medicines for human and animal use derived from biotechnology and other high-tech processes (including biosimilars) must be approved via the centralized EMA procedure.

EMA has the following guidelines regarding biosimilars:

1. Overarching Guidelines
These guidelines cover all biosimilar products:

Guideline on similar biological medicinal products
CHMP/437/04 Rev 1
Effective date: 30 April 2015
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1)
EMA/CHMP/BWP/247713/2012
Effective date: 1 December 2014
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/06/WC500167838.pdf

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substances: non-clinical and clinical issues
EMEA/CHMP/BMWP/42832/2005 Rev1
Effective date: 1 July 2015
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180219.pdf

2. Specific Guidelines
These guidelines are specific to the type of biosimilar product:

Recombinant erythropoietins
EMEA/CHMP/BMWP/301636/2008
Effective date: 1 October 2010
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/04/WC500089474.pdf

Recombinant G-CSF
EMEA/CHMP/BMWP/31329/2005
Effective date: 1 June 2006
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003955.pdf

Low molecular weight heparins
EMEA/CHMP/BMWP/118264/2007
Effective date: October 2009
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003927.pdf

Somatropin
EMEA/CHMP/BMWP/94528/2005
Effective date: 1 June 2006
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003956.pdf

Recombinant interferon alfa
EMEA/CHMP/BMWP/102046/2006
Effective date: April 2009
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003930.pdf

Monoclonal antibodies
EMA/CHMP/BMWP/403543/2010
Effective date: 1 December 2012
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/11/WC500099361.pdf

Interferon beta
EMA/CHMP/BMWP/652000/2010
Effective date: 1 September 2013
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/03/WC500139622.pdf

Recombinant r-hFSH
EMA/CHMP/BMWP/671292/2010
Effective date: 1 September 2013
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/03/WC500139624.pdf

Human insulin EMEA
CHMP/BMWP/32775/2005_Rev. 1
Effective date: 1 September 2015
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/03/WC500184161.pdf

3. Draft Specific Guidelines
EMA has the following draft guidelines under public consultation to develop guidelines for specific biosimilar products:

Revision of guideline on low molecular weight heparins
EMEA/CHMP/BMWP/118264/2007 Rev. 1
End of consultation: 31 July 2013
www.ema.europa.eu/ema/doc_index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500138309&murl=menus/document_library/document_library.jsp&mid=0b01ac058009a3dc

Revision of guideline on interferon alfa
Date: 4 January 2016
End of consultation: 31 March 2016
www.ema.europa.eu/ema/doc_index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500199346&murl=menus/document_library/document_library.jsp&mid=0b01ac058009a3dc

4. Other guidelines
Other guidelines relevant for biosimilars from EMA include:

Comparability of biotechnological/biological products ICH Topic Q 5 E
CPMP/ICH/5721/03
Effective date: June 2005
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002805.pdf

Comparability of biotechnology-derived medicinal products after a change in the manufacturing process - non-clinical and clinical issues
EMEA/CHMP/BMWP/101695/2006
Effective date: 1 November 2007
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003935.pdf

Immunogenicity assessment of biotechnology-derived therapeutic proteins
EMEA/CHMP/BMWP/14327/2006
Effective date: April 2008
www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003946.pdf

Immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use EMEA/CHMP/BMWP/86289/2010
Effective date: 1 December 2012
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/11/WC500099362.pdf

5. Draft other guidelines
EMA has the following drafts or concept papers under public consultation to develop reflection papers or for revision of guidelines relevant for biosimilars:

Draft guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins
EMEA/CHMP/BMWP/14327/2006 Rev. 1
Date: 24 September 2015
End of consultation: 31 January 2015
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/10/WC500194507.pdf

Concept paper on the revision of the guideline on recombinant G-CSF
EMA/CHMP/BMWP/214262/2015
Date: 27 July 2015
End of consultation: 31 October 2015
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/07/WC500190635.pdf

Draft concept paper on the need for a reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development
EMA/297149/2013
Date: 28 June 2013
End of consultation: 31 September 2013
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/06/WC500144945.pdf

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Source: EMA