Biologicals: active substance
HumanBiologicalsRegulatory and procedural guidanceResearch and developmentScientific guidelines
On Monday, 12 January 2026, between 07:00 and 10:00 CET (Amsterdam time), this website will be unavailable due to scheduled maintenance.
The European Medicines Agency's scientific guidelines on biological drug substances help medicine developers prepare marketing authorisation applications for human medicines.
For a complete list of scientific guidelines currently open for consultation, see Public consultations.
Manufacture, characterisation and control of the active substance
Guidelines
- ICH Q5B Analysis of the expression construct in cell lines used for production of rDNA-derived protein products
- ICH Q5D Derivation and characterisation of cell substrates used for production of biotechnologial/biological products
- ICH Q11 Development and manufacture of drug substances (chemical entities and biotechnological/biological entities)
- ICH Considerations: oncolytic viruses
- Allergen products: production and quality issues
- Development and manufacture of lentiviral vectors
- Development, production, characterisation and specifications for monoclonal antibodies and related products
- Gene therapy product quality aspects in the production of vectors and genetically modified somatic cells
- Human cell-based medicinal products
- Potency testing of cell-based immunotherapy medicinal products for the treatment of cancer
- Process validation for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submission
- Production and quality control of animal immunoglobins and immunosera for human use
- Production and quality control of medicinal products derived by recombinant DNA technology
- Quality aspects of phage therapy medicinal products
- Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells
- Quality of biological active substances produced by stable transgene expression in higher plants
- Quality of biological active substances produced by transgene expression in animals
- Quality, preclinical and clinical aspects of gene therapy medicinal products
- Use of starting materials and intermediates collected from different sources in the manufacturing of biological products
- Xenogeneic cell-based medicinal products
Reflection papers
- Design modifications of gene therapy medicinal products during development
- In-vitro cultured chondrocyte containing products for cartilage repair of the knee
- Quality, non-clinical and clinical issues relating specifically to recombinant adeno-associated viral vectors
- Stem cell-based medicinal products
Public statements
- DNA and host cell protein impurities, routine testing versus validation studies
- Use of tumorigenic cells of human origin for the production of biological and biotechnological medicinal products
Questions and answers
Specifications
Comparability and biosimilarity
Guidelines
- ICH Q5E Biotechnological/biological products subject to changes in their manufacturing process: comparability of biotechnological/biological products products
- Similar biological medicinal products
- Similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues
Reflection papers
Plasma-derived medicinal products
Guidelines
- Investigation of manufacturing processes for plasma-derived medicinal products with regard to variant Creutzfeldt-Jakob disease risk
- Plasma-derived medicinal products
- Replacement of rabbit pyrogen testing by an alternative test for plasma derived medicinal products
Reflection papers
Position statements
Plasma master file
Guidelines
- Requirements for plasma master file certification
- Scientific data requirements for plasma master file
- Epidemiological data on blood transmissible infections
- Validation of immunoassay for the detection of antibody to human immunodeficiency virus in plasma pools
- Validation of immunoassay for the detection of hepatitis B virus surface antigen in plasma pools
Position statements
- Quality and safety assessment for the plasma master file (PMF) certification with regard to donor deferral criteria for sexual risk behaviour
- Non-remunerated and remunerated donors: safety and supply of plasma-derived medicinal products
Questions and answers
Vaccines
Guidelines
- Adjuvants in vaccines for human use
- Development of vaccinia virus-based vaccines against smallpox
- Influenza vaccines - quality module
- Quality aspects of mRNA vaccines
- Quality, non-clinical and clinical aspects of live recombinant viral vectored vaccines
- Requirements for vaccine antigen master file certification
- Scientific data requirements for a vaccine antigen master file
Points to consider
Public and position statements
- Evaluation of bovine spongiform encephalopathy risk via the use of materials of bovine origin in or during the manufacture of vaccines
- Quality of water used in the production of vaccines for parenteral use
- Testing for simian virus 40 (SV40) in polio virus vaccines
- Viral safety of oral poliovirus vaccine (OPV)
Concept papers
Questions and answers