Biologicals: drug substance

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This page lists the European Medicines Agency's scientific guidance documents on biological drug substances.

If you have comments on a document that is open for consultation, use the form for submission of comments on scientific guidelines.

Table of contents

Manufacture, characterisation and control of the drug substance

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Process validation for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submission

Overview of comments

Adopted guideline

Draft guideline

EMA/CHMP/BWP/187338/2014April 20161 November 2016 
Quality of biological active substances produced by transgene expression in animals

Overview of comments

Adopted guideline

Draft guideline

Concept paper

CHMP/BWP/151897/2013June 2013December 2013 
Use of starting materials and intermediates collected from different sources in the manufacturing of biological medicinal products

Overview of comments

Adopted guideline

Draft reflection paper

CHMP/BWP/729106/2012July 2013December 2013 
Q 11 Development and manufacture of drug substances (chemical entities and biotechnological / biological entitites), Step 3Draft guidelineCHMP/ICH/425213/2011Released for consultation May 2011 Deadline for comments September 2011
Need for a guideline on process validation of medicinal products containing biotechnology derived proteins as active substanceConcept paperEMA/CHMP/BWP/25360/2011Released for consultation May 2011 Deadline for comments 31 August 2011
Production and quality control of monoclonal antibodies and related substances

Overview of comments

Adopted guideline

Draft guideline

Concept paper

CHMP/BWP/157653/07January 2009July 2009 
Potency testing of cell-based immunotherapy medicinal products for the treatment of cancer

Overview of comments

Adopted guideline

Draft guideline

CHMP/BWP/271475/06December 2007May 2008 
Quality of biological active substances produced by stable transgene expression in higher plants

Overview of comments

Adopted guideline

Draft guideline

CPMP/BWP/48316/06July 2008February 2009 
Development and manufacture of lentiviral vectorsAdopted guidelineCPMP/BWP/2458/03May 2005November 2005 
Production and quality control of animal immunoglobins and immunosera for human useAdopted guidelineCPMP/BWP/3354/99July 2002August 2002 
Human cell-based medicinal products

Overview of comments

Adopted guideline

Draft guideline

CHMP/410869/06June 2008September 2008 
Quality, preclinical and clinical aspects of gene transfer medicinal products

Adopted guideline

Concept paper

CHMP/GTWP/234523/09Release for consultation December 2009 Deadline for comments 31 March 2010
Xenogeneic cell-based medicinal products

Adopted guideline

Draft guideline

Concept paper

CHMP/CPWP/83508/09December 2009January 2010 
Quality of biotechnological products: Derivation and characterisation of cell substrates used for production of biotechnological / biological productsAdopted guidelineCPMP/ICH/294/95 ICH Topic Q5DJuly 1997March 1998 
Position statement on the use of tumorigenic cells of human origin for the production of biological and biotechnological medicinal productsAdopted guidelineCPMP/BWP/1143/00March 2001  
Position statement on DNA and host cell protein impurities, routine testing versus validation studiesAdopted guidelineCPMP/BWP/382/97June 1997June 1997 
Allergen products: Production and quality issues

Overview of comments

Adopted guideline

Draft guideline

CHMP/BWP/304831/07November 2008May 2009 
Quality of biotechnological products: Analysis of the expression construct in cell lines used for production of rDNA-derived protein productsAdopted guidelineCPMP/ICH/139/95November 1995June 1996 
Production and quality control of medicinal products derived by recombinant DNA technologyAdopted guideline3AB1A July 1995 
Gene therapy product quality aspects in the production of vectors and genetically modified somatic cellsAdopted guideline3AB6A July 1995 
Use of transgenic animals in the manufacture of biological medicinal products for human useAdopted guideline3AB7A  Superseded by CHMP/BWP/151897/2013
Production and quality control of cytokine products derived by biotechnological processAdopted guideline3AB3A August 1990 

Specifications

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Step 5 note for guidance on specifications: Test procedures and acceptance criteria for biotechnological / biological productsAdopted guidelineCPMP/ICH/365/96March 1999September 1999 
Tests on samples of biological originAdopted guideline3AB11A   

Comparability / biosimilarity

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Similar biological medicinal products containing biotechnology-derived proteins as active substance: Quality issues

Overview of comments

Adopted guideline

Draft guideline

Concept paper

CHMP/BWP/247713/2012June 2014December 2014 
Similar biological medicinal products containing biotechnology-derived proteins as active substance: Quality issuesAdopted guidelineCHMP/49348/05February 2006  
Similar biological medicinal productAdopted guidelineCHMP/437/04October 2005October 2005 
Step 5 note for guidance on biotechnological / biological products subject to changes in their manufacturing processAdopted guidelineCPMP/ICH/5721/03December 2004June 2005 
Comparability of medicinal products containing biotechnology-derived proteins as active substance - Quality issues

Adopted guideline

Concept paper

CPMP/BWP/3207/00 Rev. 1
CPMP/ICH/5721/03
December 2003December 2003Superseded by ICH Q.5.E - CPMP/ICH/5721/03

Plasma-derived medicinal products

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Viral safety of plasma-derived medicinal products with respect to hepatitis E virus

Overview of comments

Adopted reflection paper

Reflection paper

Concept paper

EMA/CHMP/BWP/723009/2014June 2016  
Plasma-derived medicinal products

Overview of comments

Adopted guideline

Draft guideline

Concept paper

CPMP/BWP/706271/2010July 2010February 2012 
Plasma-derived medicinal productsAdopted guidelineCPMP/BWP/269/95 Rev. 3January 2001January 2001 
Assessing the risk for virus transmission - New chapter 6 of the note for guidance on plasma-derived medicinal productsAdopted guidelineCPMP/BWP/5180/03October 2004October 2004 
The replacement of rabbit pyrogen testing by an alternative test for plasma derived medicinal products

Overview of comments

Adopted guideline

Draft guideline

CHMP/BWP/452081/07May 2009November 2009 
Position statement on West Nile virus and plasma-derived medicinal productsAdopted guidelineCPMP/BWP/3752/03July 2003July 2003 
Position paper on plasma-derived medicinal products: Alt testingAdopted guidelineCPMP/BWP/385/99September 1999September 1999 
Position statement on Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products

Adopted guideline

Overview of comments

Draft guideline

Concept paper

CHMP/BWP/303353/2010June 2011June 2011 
Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal productsAdopted guidelineCPMP/BWP/2879/02 Rev 1June 2004June 2004Superseded by CHMP/BWP/303353/2010
Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal productsAdopted guideline
Adopted guideline
Adopted guideline
CPMP/BWP/2879/02June 2004
February 2003
February 1998
June 2004
February 2003
February 1998
 
Investigation of manufacturing processes for plasma-derived medicinal products with regard to variant Creutzfeldt-Jakob disease riskAdopted guidelineCPMP/BWP/5136/03October 2004October 2004 

Plasma master file

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Requirements for plasma master file certificationAdopted guidelineCPMP/BWP/4663/03Feb 2004Mar 2004 
Scientific data requirements for plasma master fileAdopted guideline
Annexes
CHMP/BWP/3794/03 Rev. 1Dec 2006Jun 2007 
Epidemiological data on blood transmissible infections (plasma master file)

Adopted guideline

Appendices

Overview of comments

Draft guideline

Concept paper

CHMP/BWP/548524/2008 Rev.1Feb 2016Aug 2016 
Epidemiological data on blood transmissible infections (plasma master file)

Adopted guideline

Appendices

Overview of comments

Draft guideline

Concept paper

CHMP/BWP/548524/2008Apr 2010Mar 2011Superseded by CHMP/BWP/548524/2008 Rev.1
Epidemiological data on blood transmissible infections (plasma master file)Adopted guidelineCPMP/BWP/125/04Jan 2005Jul 2005 Superseded by CPMP/BWP/125/04 Rev.1
Position statement on non-remunerated and remunerated donors: Safety and supply of plasma-derived medicinal productsAdopted guidelineCPMP/BWP/1818/02May 2002May 2002 
Validation of immunoassay for the detection of antibody to human immunodeficiency virus in plasma pools

Overview of comments

Adopted guideline

CHMP/BWP/298388/05Sep 2006Apr 2007 
Validation of immunoassay for the detection of hepatitis B virus surface antigen in plasma pools

Overview of comments

Adopted guideline

CHMP/BWP/298390/05Sep 2006Apr 2007 

Vaccines

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Influenza vaccines - Quality module

Overview of comments

Adopted guideline

Draft quality module

Concept paper

EMA/CHMP/BWP/310834/2012

 

June 2014

 

1 November 2014  
Influenza vaccines prepared from viruses with the potential to cause a pandemic and intended for use outside of the core dossier context

Adopted guideline

Draft guideline

CHMP/VWP/263499/06July 2006February 2007 
Adjuvants in vaccines for human useAdopted guidelineCHMP/VEG/134716/04January 2005July 2005 
Explanatory note on immunomodulators for the guideline on adjuvants in vaccines for human useAdopted guidelineCHMP/VWP/244894/2006July 2006July 2006 
Dossier structure and content for pandemic-influenza-vaccine marketing-authorisation application

Adopted guideline

Draft guideline

Concept paper

CHMP/VEG/4717/03 Rev 1December 2008January 2009 
Submission of marketing-authorisation applications for pandemic influenza vaccines through the centralised procedureAdopted guidelineCPMP/4986/03April 2004April 2004 
Requirements for vaccine antigen master file certificationAdopted guidelineCPMP/4548/03/Final/ Rev 1February 2004March 2004 
Committee for Proprietary Medicinal Products position statement on the quality of water used in the production of vaccines for parenteral useAdopted guidelineCPMP/BWP/1571/02 Rev 1October 2003  
Scientific data requirements for a vaccine antigen master fileAdopted guidelineCPMP/BWP/3734/03December 2003March 2004 
Cell culture inactivated influenza vaccines

Adopted guideline

Concept paper

CPMP/BWP/2490/00January 2002August 2002Annex to CPMP/BWP/214/96
Guideline on quality aspects on the isolation of candidate influenza vaccine viruses in cell culture

Overview of comments

Adopted guideline

Draft guideline

Concept paper

CHMP/BWP/368186/2011August 2011February 2012 
Points to consider on the development of live attenuated influenza vaccines

Adopted guideline

Concept paper

CPMP/BWP/2289/01February 2003August 2003 
Development of Vaccinia virus-based vaccines against smallpoxAdopted guidelineCPMP/1100/02June 2002July 2002 
Development of a Committee for Proprietary Medicinal Products note for guidance on the on requirements for the evaluation of new adjuvants in vaccinesConcept paperCPMP/BWP/6622/02April 2002  
Points to consider on the reduction, elimination or substitution of thiomersal in vaccinesAdopted guidelineCPMP/BWP/2517/00April 2001May 2001 
Public statement on the evaluation of bovine-spongiform-encephalopathy risk via the use of materials of bovine origin in or during the manufacture of vaccinesAdopted guidelineCPMP/BWP/476/01February 2001February 2001 
Development of Committee for Proprietary Medicinal Products points to consider on stability and traceability requirements for vaccine intermediatesConcept paperCPMP/BWP/4310/002000  
Pharmaceutical and biological aspects of combined vaccinesAdopted guidelineCPMP/BWP/477/97July 1998January 1999 
Harmonisation of requirements for influenza vaccinesAdopted guidelineCPMP/BWP/214/96March 1997April 1997 

Stability

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TopicDocumentsReference numberPublication dateEffective dateRemarks
Quality of biotechnological products: Stability testing of biotechnological / biological productsAdopted guidelineCPMP/ICH/138/95 July 1996 

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