Market access for ATMPs
BINDING EU TEXTS
- Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, OJ L 311, 28.11.2001, p. 67–128, CELEX number: 32001L0083, as amended.
- Directive 2009/53/EC of the European Parliament and of the Council of 18 June 2009 amending Directive 2001/82/EC and Directive 2001/83/EC, as regards variations to the terms of marketing authorisations for medicinal products (Text with EEA relevance), OJ L 168, 30.6.2009, p. 33–34, CELEX number: 32009L0053
- Proposal (Proposal for a Directive of the European Parliament and of the Council amending Directive 2001/82/EC and Directive 2001/83/EC as regards variations to the terms of marketing authorisations for medicinal products {SEC (2008) 273} {SEC (2008) 274}, COM/2008/0123 final - COD 2008/0045, CELEX number: 52008PC0123)
- Original text
- Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (Text with EEA relevance), OJ L 334, 12.12.2008, p. 7–24, CELEX number: 32008R1234
Action Plan on ATMPs
- European Commission DG Health and Food Safety and European Medicines Agency, Action Plan on ATMPs, 20 October 2017, European Commission
Marketing authorization pathway
Standard approval process: centralized procedure
GUIDELINES
- EMA, Procedural advice on the evaluation of ATMPs, EMA/630043/2008, 25 January 2018
- EMA, CAT, Procedural advice on the evaluation of combined advanced therapy medicinal products and the consultation of Notified Bodies in accordance with Article 9 of Regulation (EC) No. 1394/2007, EMA/354785/2010, 11 February 2011
- EMA, CHMP, Procedural advice on the re-examination of CHMP opinions, EMEA/CHMP/50745/2005 Rev.1, 12 February 2009
- EMA, Administration and Corporate Management Division, Dossier requirements for centrally authorised products (CAPs), EMA/497021/2012 Rev. 26, 4 January 2021
- EMA, CHMP, CVMP, Recommendation to marketing authorisation holders, highlighting the need to ensure compliance with 3Rs methods described in the European Pharmacopoeia, EMA/CHMP/CVMP/JEG-3Rs/252137/2012, 12 July 2012
Marketing Authorisation Application file
GUIDELINES
- EMA, Guide on Advanced Therapy Medicinal Products- Quality Flowchart and Checklist, 29 November 2021
- EMA, Guide on Advanced Therapy Medicinal Products- Non- Clinical Development Flowchart and Checklist, 29 November 2021
- EMA, Guide on Advanced Therapy Medicinal Products- Clinical Developement Flowchart and Checklist, 29 November 2021
- EMA, CHMP, Guideline on environmental risk assessments for medicinal products consisting of, or containing, genetically modified organisms (GMOs), EMEA/CHMP/BWP/473191/2006, 11 December 2006,
- EMA, Heads of Medicines Agency, (EU innovation Network), Genome editing, EU-IN Horizon Scanning Report, EMA/319248/2020, 15 February 2021
- EMA, CHMP, Guideline on excipients in the dossier for application for marketing authorisation of a medicinal product, EMEA/CHMP/QWP/396951/2006, 19 June 2007
- EMA, CPMP, ICH Q2 (R1) Validation of analytical procedures: text and methodology, CPMP/ICH/381/95, June 1995
- EMA, CPMP, ICH Q5A (R1) Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin, CPMP/ICH/295/95, October 1997
- EMA, CPMP, ICH Q5C Stability testing of biotechnological/biological products, CPMP/ICH/138/95, July 1996
- EMA, CPMP, ICH Q5D Derivation and characterisation of cell substrates used for production of biotechnological/biological products, CPMP/ICH/294/95, March 1998
- EMA, CPMP, ICH Q5E Comparability of biotechnological/biological products, CPMP/ICH/5721/03, June 2005
- EMA, CPMP, ICH Q6B Specifications: Test procedures and acceptance criteria for biotechnological/biological products, CPMP/ICH/365/96, September 1999
- EMA, CPMP, ICH Q7 Good manufacturing practice for active pharmaceutical ingredients, CPMP/ICH/4106/00, November 2000
- EMA, CHMP, ICH Q8 (R2) Pharmaceutical development, CHMP/ICH/167068/04, 22 June 2017
- EMA, CHMP, Draft ICH guideline Q9 (R1) on quality risk management, Step 2b, EMA/CHMP/ICH/24235/2006, 16 December 2021, UNDER CONSULTATION
- EMA, CHMP, ICH Q9 Quality risk management – Step 5, EMA/CHMP/ICH/24235/2006, September 2015
- EMA, CHMP, ICH Q10 Pharmaceutical quality system, EMA/CHMP/ICH/214732/2007, September 2015
- EMA, CPMP, ICH E1 The extent of population exposure to assess clinical safety, CPMP/ICH/375/95, June 1995
- EMA, CPMP, ICH E3 Structure and content of clinical study reports, CPMP/ICH/137/95, July 1996
- EMA, CPMP, ICH E4 Dose response information to support drug registration, CPMP/ICH/378/95, November 1994
- EMA, CHMP, ICH E6 (R2) Good clinical practice Step 5, CPMP/ICH/135/95, 1 December 2016
- EMA, CPMP, ICH E7 Geriatrics, CPMP/ICH/379/95, March 1994
- EMA, CPMP, ICH E8 General considerations for clinical trials, CPMP/ICH/291/95, March 1998
- EMA, CPMP, ICH guideline E10 on choice of control groups in clinical trials, CPMP/ICH/364/96, January 2001
- EMA, CHMP, ICH E11 (1) Clinical investigation of medicinal products in the paediatric population, CPMP/ICH/2711/99, 1 September 2017
- EMA, CPMP, ICH guideline M3 (R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals, EMA/CPMP/ICH/286/1995, December 2009
- EMA, CHMP, ICH guideline S2 (R1) on genotoxicity testing and data interpretation for pharmaceuticals intended for human use, EMA/CHMP/ICH/126642/2008, June 2012
- EMA, CHMP, ICH S5 (R3) guideline on reproductive toxicology: Detection of toxicity to reproduction for human pharmaceuticals - step 5, EMA/CHMP/ICH/544278/1998, 17 February 2020
- EMA, CHMP, ICH guideline S6 (R1) on Preclinical safety evaluation of biotechnology-derived pharmaceuticals, CHMP/ICH/731268/1998, June 2011
- EMA, CPMP, ICH guideline S7A on Safety pharmacology studies for human pharmaceuticals, CPMP/ICH/539/00, June 2001
- EMA, CHMP, ICH guideline S8 Immunogenicity studies for human pharmaceuticals, CHMP/167235/2004, May 2006
- EMA, CHMO, CAT, Creutzfeldt-Jakob disease and advanced therapy medicinal products, EMA/CHMP/BWP/353632/2010, 23 June 2011
- EMA, Note for guidance on Development pharmaceutics for biotechnological and biological products, CPMP/BWP/328/99, 21 October 1999
- EMA, CPMP, Annex to Note for guidance on development pharmaceutics, CPMP/QWP/155/96, 21 October 1999
- Existing clinical guidance for the studied indication(s)
For GTMP
- EMA, CAT, Quality, preclinical and clinical aspects of gene therapy medicinal products, EMA/CAT/80183/2014, 22 March 2018
- EMA, CAT, Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells, EMA/CAT/GTWP/671639/2008 Rev. 1 – corr, 12 November 2020
- EMA, CHMP, Potency testing of cell-based immunotherapy medicinal products for the treatment of cancer, EMA/CHMP/BWP/271475/2006 rev.1, 21 July 2016
- EMA, CHMP, Development and manufacture of lentiviral vectors, CHMP/BWP/2458/03, 26 May 2005
- EMA, CHMP, Non-clinical studies required before first clinical use of gene therapy medicinal products, EMEA/CHMP/GTWP/125459/2006, 30 May 2008
- EMA, CHMP, Non-clinical testing for inadvertent germline transmission of gene transfer vectors, EMEA/273974/2005, 16 November 2006
- EMA, CHMP, Follow-up of patients administered with gene therapy medicinal products, EMEA/CHMP/GTWP/60436/2007, 22 October 2009
- EMA, CHMP, Scientific requirements for the environmental risk assessment of gene-therapy medicinal products, CHMP/GTWP/125491/06, 30 May 2008
- EMA, CHMP, Guideline on quality, non-clinical and clinical aspects of live recombinant viral vectored vaccines, EMA/CHMP/VWP/141697/2009, 24 June 2010
- EMA, CHMP, Guideline on development and manufacture of lentiviral vectors, CHMP/BWP/2458/03, 26 May 2005
- EMA, CPMP, ICH Q5B Analysis of the expression construct in cell lines used for production of r-DNA derived protein products, CPMP/ICH/139/95, July 1996
- EMA, CHMP, ICH guideline S12 on nonclinical biodistribution considerations for gene therapy products - Step 2b, EMA/CHMP/ICH/318372/2021, 24 June 2021
- EMA, CHMP, General principles to address the risk of inadvertent germline integration of gene therapy vectors, CHMP/ICH/469991/2006, November 2006
- EMA, CHMP, ICH Considerations: general principles to address virus and vector shedding, EMEA/CHMP/ICH/449035/2009, July 2009
- EMA, CHMP, ICH Considerations: oncolytic viruses, EMEA/CHMP/ICH/607698/2008, October 2009
- EMA, CAT, Design modifications of gene therapy medicinal products during development, EMA/CAT/GTWP/44236/2009, 14 December 2011
- EMA, CHMP, Quality, non-clinical and clinical issues relating specifically to recombinant adeno-associated viral vectors, CHMP/GTWP/587488/2007 Rev.1, 24 June 2010
- EMA, CAT, Management of clinical risks deriving from insertional mutagenesis, EMA/CAT/190186/2012, 19 April 2013
- EMA, CHMP, Questions and answers on gene therapy, EMA/CAT/80183/2014, 17 December 2009
- EMA, CPMP, CPMP position statement on DNA and Host Cell Proteins (HCP) impurities, routine testing versus validation studies, CPMP/BWP/382/97, 10 June 1997
- EMA, CPMP, Note for guidance on virus validation studies: The design, contribution and interpretation of studies validating the inactivation and removal of viruses, CPMP/BWP/268/95 or 3AB8A, 14 February 1996
- Ph.Eur chapter 2.6.16. Tests for extraneous agents in viral vaccines for human use (01/2011:20616)
- Ph.Eur. General chapter 5.1.7 on viral safety (01/2008:50107)
- Ph.Eur. General chapter 5.2.3 on Cell substrates for the production of vaccines for human use (01/2017:50203)
- Ph.Eur. General chapter 5.2.12. Raw materials of biological origin for the production of cell based and gene therapy medicinal products (01/2017:50212)
- Ph.Eur. General chapter 5.14 on Gene transfer medicinal products for human use (01/2010:51400)
- Ph.Eur. General chapter 5.15. Functionality-related characteristics of excipients (07/2017:51500)
For Cell Therapy and Tissue Engineered Products
- EMA, CAT, Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells, EMA/CAT/GTWP/671639/2008 Rev. 1 – corr, 12 November 2020
- EMA, CHMP, Human cell-based medicinal products, EMEA/CHMP/410869/2006, 21 May 2008,
- EMA, CHMP, Guideline on Potency testing of cell-based immunotherapy medicinal products for the treatment of cancer, EMA/CHMP/BWP/271475/2006 rev.1, 21 July 2016
- EMA, CHMP, Xenogeneic cell-based medicinal products, EMEA/CHMP/CPWP/83508/2009, 22 October 2009
- EMA, CAT, Clinical aspects related to tissue engineered products, EMA/CAT/573420/2009, 19 September 2014
- EMA, CAT, In-vitro cultured chondrocyte containing products for cartilage repair of the knee, EMA/CAT/CPWP/568181/2009, 8 April 2010
- EMA, CAT, Stem cell-based medicinal products, EMA/CAT/571134/2009, 14 January 2011
- Ph.Eur. monograph on human haematopoietic stem cells (Cellulae stirpes haematopoieticae humanae) Version 7.2
- Ph.Eur. monograph on Method of analysis (2.7.23.) Numeration of CD34/CD45+ cells in haematopoietic products. Version 7.2
- Ph.Eur. monograph on Method of analysis (2.7.28.) Colony-forming cell assay for human haematopoietic progenitor cells. Version 7.2
- Ph.Eur. monograph on Nucleated Cell Count and Viability (2.7.29.)
- Ph.Eur. monograph on Nucleic Acid Amplification Techniques (2.6.21.)
- Ph.Eur. monograph on Flow Cytometry (2.7.24.)
- Ph.Eur: (2.6.27) Microbiological control of cellular products
- Ph.Eur: (2.6.1.) Sterility
- Ph.Eur: (5.1.6) Alternative methods for control of microbiological quality
- Ph.Eur. monograph Mycoplasmas (2.6.7.)
- Ph.Eur. monograph on Bacterial endotoxins (2.6.14.)
- General chapter 5.2.12 Raw materials for the production of cell-based and gene therapy medicinal products
Expediting access pathways
Conditional MA
BINDING EU TEXT
- Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Text with EEA relevance), OJ L 136, 30.4.2004, p. 1–33, CELEX number: 32004R0726
- Commission Regulation (EC) No 507/2006 of 29 March 2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004 of the European Parliament and of the Council (Text with EEA relevance), OJ L 92, 30.3.2006, p. 6–9, CELEX number: 32006R0507
GUIDELINES
Guideline on the scientific application and the practical arrangements necessary to implement Regulation (EC) No 507/2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004
MA under exceptional circumstances
BINDING EU TEXTS
- Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Text with EEA relevance), OJ L 136, 30.4.2004, p. 1–33, CELEX number: 32004R0726
- Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, OJ L 311, 28.11.2001, p. 67–128, CELEX number: 32001L0083, as amended.
GUIDELINES
- EMA, guideline on procedures for the granting of a marketing authorisation under exceptional circumstances, 15 December 2005, EMEA/357981/2005
Accelerated Assessment
BINDING EU TEXTS
- Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Text with EEA relevance), OJ L 136, 30.4.2004, p. 1–33, CELEX number: 32004R0726
GUIDELINES AND OTHER EMA GUIDANCE DOCUMENTS
- EMA, Guideline on the procedure for accelerated assessment pursuant to article 14 (9) of Regulation (EC) No 726/2004, 17 July 2006, EMEA/419127/05
Biosimilars
BINDING EU TEXTS
- Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, OJ L 311, 28.11.2001, p. 67–128, CELEX number: 32001L0083, as amended.
- Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Text with EEA relevance), OJ L 136, 30.4.2004, p. 1–33, CELEX number: 32004R0726
GUIDELINES AND OTHER EMA GUIDANCE DOCUMENTS
- EMA, European Medicines Agency procedural advice for users of the centralised procedure for similar biological medicinal products applications, 19 August 2019, EMA/940451/2011
- EMA, Tailored scientific advice to support step-by-step development of new biosimilars, 30 September 2021, EMA/289230/2021
- EMA, Guideline on similar biological medicinal products, 23 October 2014, CHMP/437/04 Rev 1
- EMA, Guideline on Similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues, 18 December 2014, EMEA/CHMP/BMWP/42832/2005 Rev1
- EMA, Guideline on Similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues, 22 May 2014, EMA/CHMP/BWP/247713/2012
- See also product-specific biosimilar guidelines as well as other relevant guidelines for biosimilars
EMA regulatory support schemes
PRIME
GUIDELINES
- EMA, Human Medicines Research and Development Support Division, European Medicines Agency Guidance for applicants seeking access to PRIME scheme, EMA/191104/20157 May 2018
- EMA, CHMP, Draft toolbox guidance on scientific elements and regulatory tools to support quality data packages for PRIME marketing authorisation applications, EMA/CHMP/BWP/QWP/IWG/694114/2019, 2 February 2021
- EMA, Human Medicines Evaluation Division, European Medicines Agency Guidance on interactions in the context of PRIME, EMA/205771/2016, 7 May 2018
- EMA, Decision of the Executive Director on fee reductions for scientific advice requests on PRIME products for SMEs and applicants from the academic sector, EMA/63484/2016, 27 May 2016
- EMA, CHMP, Enhanced early dialogue to facilitate accelerated assessment of PRIority Medicines (PRIME), EMA/CHMP/57760/2015, Rev. 1, 7 May 2018
- EMA, Human Medicines Research and Development Support Division, Meeting report: Workshop with stakeholders on support to quality development in early access approaches, such as PRIME and Breakthrough Therapies, 26 November 2018, European Medicines Agency, London, EMA/CHMP/BWP/812924/2018, 25 July 2019
Adaptive pathways
GUIDELINES AND OTHER GUIDANCE DOCUMENTS
- EMA, Guidance for companies considering the adaptive pathways approach, 1 August 2016, EMA/527726/2016