Research and Innovation Binding Text and Guidance

• EMA, CAT, Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials, EMA/CAT/852602/2018, 31 January 2019
• EMA, CHMP, Guideline on safety and efficacy follow-up and risk management of advanced therapy medicinal products, EMEA/149995/2008, 20 November 2008
  • UNDER REVISION
• EMA, CAT, Risk-based approach according to Annex I, part IV of Directive 2001/83/EC applied to Advanced Therapy Medicinal Products, EMA/CAT/CPWP/686637/2011, 11 February 2013
• EMA, Inspections, Human Medicines, Pharmacovigilance and Committees Division, Development of non-substantially manipulated cell-based ATMPs : flexibility introduced via the application of the risk-based approach, EMA/CAT/216556/2017, 3 July 2017
• 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, CHMO, CAT, Creutzfeldt-Jakob disease and advanced therapy medicinal products, EMA/CHMP/BWP/353632/2010, 23 June 2011
• EMA, Heads of Medicines Agency, (EU innovation Network), Genome editing, EU-IN Horizon Scanning Report, EMA/319248/2020, 15 February 2021

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, 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. chapter 5.1.7 on viral safety (01/2008:50107)
• Ph.Eur. chapter 5.2.3 on Cell substrates for the production of vaccines for human use (01/2017:50203)
• Ph.Eur.  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. chapter 5.14  Gene transfer medicinal products for human use (01/2010:51400)
• Ph.Eur. 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 on Mycoplasmas (2.6.7.)
• Ph.Eur. monograph on Bacterial endotoxins (2.6.14.)
• Ph.Eur. chapter 5.2.12 Raw materials for the production of cell-based and gene therapy medicinal products

Genetically Modified Organisms (GMOs) 

• Regulation (EU) 2020/1043 of the European Parliament and of the Council of 15 July 2020 on the conduct of clinical trials with and supply of medicinal products for human use containing or consisting of genetically modified organisms intended to treat or prevent coronavirus disease (COVID-19), OJ L 231, 17.7.2020, p. 12–16, CELEX number: 32020R1043 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council on the conduct of clinical trials with and supply of medicinal products for human use containing or consisting of genetically modified organisms intended to treat or prevent coronavirus disease, COM/2020/261 final, CELEX number: 52020PC0261) 
  • Original text 
• Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms (Recast) (Text with EEA relevance), OJ L 125, 21.5.2009, p. 75–97, CELEX number: 32009L0041 
  • Proposal (Proposal for a Directive of the European Parliament and of the Council on the contained use of genetically modified micro-organisms (Recast), COM/2007/0736 final - COD 2007/0259, CELEX number: 52007PC0736) 
  • Original text 
  • Document summary 
• 2000/608/EC: Commission Decision of 27 September 2000 concerning the guidance notes for risk assessment outlined in Annex III of Directive 90/219/EEC on the contained use of genetically modified micro-organisms (notified under document number C(2000) 2736) (Text with EEA relevance), OJ L 258, 12.10.2000, p. 43–48, CELEX number: 32000D0608 
  • Original text 
• Regulation (EC) No 1946/2003 of the European Parliament and of the Council of 15 July 2003 on transboundary movements of genetically modified organisms (Text with EEA relevance), OJ L 287, 5.11.2003, p. 1–10, CELEX number: 32003R1946 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council on the transboundary movement of genetically modified organisms, COM/2002/0085 final - COD 2002/0046, OJ C 151 E, 25.6.2002, p. 121–128, CELEX number: 52002PC0085) 
  • Original text 
  • Document summary 
• Commission Implementing Decision (EU) 2021/1161 of 13 July 2021 amending Decision 2011/891/EU and Implementing Decisions (EU) 2017/1211, (EU) 2017/1212, (EU) 2017/2449, (EU) 2019/2085 and (EU) 2019/2086 as regards the authorisation holder and its representative in the Union for the placing on the market of products containing, consisting of, or produced from certain genetically modified organisms (notified under document C(2021) 5148) (Text with EEA relevance) (Only the Dutch text is authentic), C/2021/5148, OJ L 252, 15.7.2021, p. 1–6, CELEX number: 32021D1161 
  • Original text 
• Commission Implementing Decision (EU) 2021/184 of 12 February 2021 amending Decisions 2009/813/EC, 2009/814/EC and 2010/429/EU and Implementing Decisions 2012/82/EU, 2012/83/EU, 2012/347/EU, 2013/649/EU, (EU) 2015/683, (EU) 2015/684, (EU) 2015/685, (EU) 2015/686, (EU) 2015/687, (EU) 2015/688, (EU) 2015/689, (EU) 2015/693, (EU) 2015/695, (EU) 2015/696, (EU) 2015/700, (EU) 2015/701, (EU) 2015/2279, (EU) 2015/2281, (EU) 2016/1216, (EU) 2016/1217, (EU) 2017/1207, (EU) 2018/1111, (EU) 2018/2045, (EU) 2018/2046, (EU) 2019/1307, (EU) 2019/1308, (EU) 2019/1309, (EU) 2019/2083 and (EU) 2020/1360 as regards the authorisation holder and its representative in the Union for the placing on the market of products containing, consisting of or produced from certain genetically modified organisms (notified under document C(2021) 826) (Only the Dutch text is authentic) (Text with EEA relevance), C/2021/826, OJ L 55, 16.2.2021, p. 4–23, CELEX number: 32021D0184 
  • Original text 
• Regulation (EU) 2019/1381 of the European Parliament and of the Council of 20 June 2019 on the transparency and sustainability of the EU risk assessment in the food chain and amending Regulations (EC) No 178/2002, (EC) No 1829/2003, (EC) No 1831/2003, (EC) No 2065/2003, (EC) No 1935/2004, (EC) No 1331/2008, (EC) No 1107/2009, (EU) 2015/2283 and Directive 2001/18/EC (Text with EEA relevance.), OJ L 231, 6.9.2019, p. 1–28, CELEX number: 32019R1381 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council on the transparency and sustainability of the EU risk assessment in the food chain amending Regulation (EC) No 178/2002 [on general food law], Directive 2001/18/EC [on the deliberate release into the environment of GMOs], Regulation (EC) No 1829/2003 [on GM food and feed], Regulation (EC) No 1831/2003 [on feed additives], Regulation (EC) No 2065/2003 [on smoke flavourings], Regulation (EC) No 1935/2004 [on food contact materials], Regulation (EC) No 1331/2008 [on the common authorisation procedure for food additives, food enzymes and food flavourings], Regulation (EC) No 1107/2009 [on plant protection products] and Regulation (EU) No 2015/2283 [on novel foods], COM/2018/0179 final - 2018/088 (COD), CELEX number: 52018PC0179) 
  • Original text 
  • Document summary 

• Commission Directive (EU) 2018/350 of 8 March 2018 amending Directive 2001/18/EC of the European Parliament and of the Council as regards the environmental risk assessment of genetically modified organisms, OJ L 67, 9.3.2018, p. 30–45, CELEX number: 32018L0350 
  • Original text 
• Commission Implementing Regulation (EU) No 120/2014 of 7 February 2014 amending Regulation (EC) No 1981/2006 on detailed rules for the implementation of Article 32 of Regulation (EC) No 1829/2003 of the European Parliament and the Council as regards the Community reference laboratory for genetically modified organisms Text with EEA relevance, OJ L 39, 8.2.2014, p. 46–52, CELEX number: 32014R0120 
  • Original text 
• 2009/770/EC: Commission Decision of 13 October 2009 establishing standard reporting formats for presenting the monitoring results of the deliberate release into the environment of genetically modified organisms, as or in products, for the purpose of placing on the market, pursuant to Directive 2001/18/EC of the European Parliament and of the Council (notified under document C(2009) 7680) (Text with EEA relevance), OJ L 275, 21.10.2009, p. 9–27, CELEX number: 32009D0770 
  • Original text 
• Directive 2008/27/EC of the European Parliament and of the Council of 11 March 2008 amending Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, as regards the implementing powers conferred on the Commission, OJ L 81, 20.3.2008, p. 45–47, CELEX number: 32008L0027 
  • Proposal (Proposal for a Directive of the European Parliament and of the Council Amending Directive 2001/18/CE concerning the deliberate release into the environment of genetically modified organisms, as regards the implementing powers conferred to the Commission, COM/2006/0920 final - COD 2006/0296, CELEX number: 52006PC0920) 
  • Original text 
• Commission Regulation (EC) No 1981/2006 of 22 December 2006 on detailed rules for the implementation of Article 32 of Regulation (EC) No 1829/2003 of the European Parliament and of the Council as regards the Community reference laboratory for genetically modified organisms (Text with EEA relevance), OJ L 368, 23.12.2006, p. 99–109, CELEX number: 32006R1981 
  • Original text 
  • Consolidated text 
• Commission Regulation (EC) No 65/2004 of 14 January 2004 establishing a system for the development and assignment of unique identifiers for genetically modified organisms, OJ L 10, 16.1.2004, p. 5–10, CELEX number: 32004R0065 
  • Original text 
  • Document summary 
• 2002/813/EC: Council Decision of 3 October 2002 establishing, pursuant to Directive 2001/18/EC of the European Parliament and of the Council, the summary notification information format for notifications concerning the deliberate release into the environment of genetically modified organisms for purposes other than for placing on the market, OJ L 280, 18.10.2002, p. 62–83, CELEX number: 32002D0813 
  • Original text 
  • Consolidated text 
• 2002/812/EC: Council Decision of 3 October 2002 establishing pursuant to Directive 2001/18/EC of the European Parliament and of the Council the summary information format relating to the placing on the market of genetically modified organisms as or in products, OJ L 280, 18.10.2002, p. 37–61, CELEX number: 32002D0812 
  • Original text 
• 2002/811/EC: Council Decision of 3 October 2002 establishing guidance notes supplementing Annex VII to Directive 2001/18/EC of the European Parliament and of the Council on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC, OJ L 280, 18.10.2002, p. 27–36, CELEX number: 32002D0811 
  • Proposal (Proposal for a Council Decision establishing guidance notes supplementing Annex VII to Directive 2001/18/EC of the European Parliament and of the Council on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC /* COM/2002/0359 final */ OJ C 262E , 29.10.2002, p. 325–335) 
  • Original text 
• Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC - Commission Declaration, OJ L 106, 17.4.2001, p. 1–39, CELEX number: 32001L0018 
  • Proposal (Proposal for a European Parliament and Council Directive amending Directive 90/220/EEC on the deliberate release into the environment of genetically modified organisms, COM/98/0085 final - COD 98/0072, OJ C 139, 4.5.1998, p. 1, CELEX number: 51998PC0085) 
  • Amended proposal (Amended proposal for a European Parliament and Council Directive amending Directive 90/220/EEC on the deliberate release into the environment of genetically modified organisms, COM/99/0139 final - COD 98/0072, OJ C 139, 19.5.1999, p. 7, CELEX number: 51999PC0139) 
  • Original text 
  • Consolidated text 
  • Document summary 
• 96/134/EC: Commission Decision of 16 January 1996 amending Decision 91/448/EEC concerning guidelines for classification referred to in Article 4 of Council Directive 90/219/EEC on the contained use of genetically modified micro-organisms (Text with EEA relevance), OJ L 31, 9.2.1996, p. 25–27, CELEX number: 31996D0134 
  • Original text 
• 93/572/EEC: Commission Decision of 19 October 1993 concerning the placing on the market of a product containing genetically modified organisms pursuant to Article 13 of Council Directive 90/220/EEC, OJ L 276, 9.11.1993, p. 16–17, CELEX number: 31993D0572 
  • Original text 
• 91/596/EEC: Council Decision of 4 November 1991 concerning the Summary Notification Information Format referred to in Article 9 of Directive 90/220/EEC on the deliberate release into the environment of genetically modified organisms, OJ L 322, 23.11.1991, p. 1–16, CELEX number: 31991D0596 
  • Proposal (Proposal For A Council Decision Concerning The Summary Notification Information Format Referred To In Article 9 Of Directive 90/220/Eec/* Com/91/282final */) 
  • Original text 
  • Consolidated text 

Medical Devices (MD) 

• Commission Implementing Decision (EU) 2022/6 of 4 January 2022 amending Implementing Decision (EU) 2021/1182 as regards harmonised standards for biological evaluation of medical devices, sterilisation of health care products, aseptic processing of health care products, quality management systems, symbols to be used with information to be supplied by the manufacturer, processing of health care products and home light therapy equipment, C/2022/9, OJ L 1, 5.1.2022, p. 11–13, CELEX number: 32022D0006 
  • Original text 

• Commission Implementing Regulation (EU) 2021/2226 of 14 December 2021 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards electronic instructions for use of medical devices, C/2021/8984, OJ L 448, 15.12.2021, p. 32–38, CELEX number: 32021R2226 
  • Original text 
• Commission Implementing Regulation (EU) 2021/2078 of 26 November 2021 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards the European Database on Medical Devices (Eudamed), C/2021/8447, OJ L 426, 29.11.2021, p. 9–15, CELEX number: 32021R2078 
  • Original text  
• Commission Delegated Directive (EU) 2021/1978 of 11 August 2021 amending, for the purposes of adapting to scientific and technical progress, Annex IV to Directive 2011/65/EU of the European Parliament and of the Council as regards an exemption for the use of bis(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) in spare parts recovered from and used for the repair or refurbishment of medical devices (Text with EEA relevance), C/2021/5866, OJ L 402, 15.11.2021, p. 65–68, CELEX number: 32021L1978 
  • Original text 
• Commission Implementing Decision (EU) 2021/1182 of 16 July 2021 on the harmonised standards for medical devices drafted in support of Regulation (EU) 2017/745 of the European Parliament and of the Council, C/2021/5210, OJ L 256, 19.7.2021, p. 100–102, CELEX number: 32021D1182 
  • Original text 
• Commission Implementing Decision (EU) 2021/611 of 14 April 2021 amending Implementing Decision (EU) 2020/438 as regards harmonised standards on biological evaluation of medical devices, packaging for terminally sterilised medical devices, sterilisation of health care products and clinical investigation of medical devices for human subjects, C/2021/2434, OJ L 129, 15.4.2021, p. 158–160, CELEX number: 32021D0611 
  • Original text 
• Commission Implementing Decision (EU) 2021/610 of 14 April 2021 amending Implementing Decision (EU) 2020/437 as regards harmonised standards on medical vehicles and their equipment, anaesthetic and respiratory equipment, biological evaluation of medical devices, packaging for terminally sterilised medical devices, sterilisation of health care products, clinical investigation of medical devices for human subjects, non-active surgical implants, medical devices utilising animal tissues and their derivatives, electroacoustics and medical electrical equipment, C/2021/2439, OJ L 129, 15.4.2021, p. 153–157, CELEX number: 32021D0610 
  • Original text 
• Commission Implementing Decision (EU) 2021/609 of 14 April 2021 amending Implementing Decision (EU) 2020/439 as regards harmonised standards on packaging for terminally sterilised medical devices and sterilisation of health care products, C/2021/2432, OJ L 129, 15.4.2021, p. 150–152, CELEX number: 32021D0609 
  • Original text 
• Regulation (EU) 2020/561 of the European Parliament and of the Council of 23 April 2020 amending Regulation (EU) 2017/745 on medical devices, as regards the dates of application of certain of its provisions (Text with EEA relevance), OJ L 130, 24.4.2020, p. 18–22, CELEX number: 32020R0561 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council amending Regulation (EU) 2017/745 on medical devices as regards the dates of application of certain of its provisions (Text with EEA relevance), COM(2020) 144 final, 2020/0060(COD) 
  • Original text 
• Commission Implementing Decision (EU) 2020/439 of 24 March 2020 on the harmonised standards for in vitro diagnostic medical devices drafted in support of Directive 98/79/EC of the European Parliament and of the Council, C/2020/1903, OJ L 90I, 25.3.2020, p. 33–39, CELEX number: 32020D0439 
  • Original text  
  • Consolidated text 
• Commission Implementing Decision (EU) 2020/438 of 24 March 2020 on the harmonised standards for active implantable medical devices drafted in support of Council Directive 90/385/EEC, C/2020/1902, OJ L 90I, 25.3.2020, p. 25–32, CELEX number: 32020D0438 
  • Original text  
  • Consolidated text 
• Commission Implementing Decision (EU) 2020/437 of 24 March 2020 on the harmonised standards for medical devices drafted in support of Council Directive 93/42/EEC, C/2020/1901, OJ L 90I, 25.3.2020, p. 1–24, CELEX number: 32020D0437 
  • Original text 
  • Consolidated text 
• Commission Implementing Decision (EU) 2019/1396 of 10 September 2019 laying down the rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards the designation of expert panels in the field of medical devices (Text with EEA relevance.), C/2019/6414, OJ L 234, 11.9.2019, p. 23–30, CELEX number: 32019D1396 
  • Original text 
• Commission Implementing Decision (EU) 2019/939 of 6 June 2019 designating issuing entities designated to operate a system for the assignment of Unique Device Identifiers (UDIs) in the field of medical devices (Text with EEA relevance.), C/2019/4068, OJ L 149, 7.6.2019, p. 73–75, CELEX number: 32019D0939 
  • Original text 
• Commission Implementing Regulation (EU) 2017/2185 of 23 November 2017 on the list of codes and corresponding types of devices for the purpose of specifying the scope of the designation as notified bodies in the field of medical devices under Regulation (EU) 2017/745 of the European Parliament and of the Council and in vitro diagnostic medical devices under Regulation (EU) 2017/746 of the European Parliament and of the Council (Text with EEA relevance. ), C/2017/7779, OJ L 309, 24.11.2017, p. 7–17, CELEX number: 32017R2185 
  • Original text 
• Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance), OJ L 117, 5.5.2017, p. 1–175, CELEX number: 32017R0745 
  • Proposal (Proposal for a Regulation of the European Parliament and the Council on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009, COM/2012/0542 final, 2012/0266 (COD), CELEX number: 52012PC0542) 
  • Original text 
  • Consolidated text 
  • Document summary 
• Commission Implementing Regulation (EU) No 920/2013 of 24 September 2013 on the designation and the supervision of notified bodies under Council Directive 90/385/EEC on active implantable medical devices and Council Directive 93/42/EEC on medical devices Text with EEA relevance, OJ L 253, 25.9.2013, p. 8–19, CELEX number: 32013R0920 
  • Original text 
  • Consolidated text 
• Commission Regulation (EU) No 207/2012 of 9 March 2012 on electronic instructions for use of medical devices Text with EEA relevance, OJ L 72, 10.3.2012, p. 28–31, CELEX number: 32012R0207 
  • Original text 
• 2010/227/: Commission Decision of 19 April 2010 on the European Databank on Medical Devices (Eudamed) (notified under document C(2010) 2363) (Text with EEA relevance), OJ L 102, 23.4.2010, p. 45–48, CELEX number: 32010D0227 
  • Original text 
• Commission Directive 2005/50/EC of 11 August 2005 on the reclassification of hip, knee and shoulder joint replacements in the framework of Council Directive 93/42/EEC concerning medical devices (Text with EEA relevance), OJ L 210, 12.8.2005, p. 41–43, CELEX number: 32005L0050 
  • Original text 
• Commission Directive 2003/12/EC of 3 February 2003 on the reclassification of breast implants in the framework of Directive 93/42/EEC concerning medical devices (Text with EEA relevance), OJ L 28, 4.2.2003, p. 43–44, CELEX number: 32003L0012 
  • Original text 
• Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance), OJ L 117, 5.5.2017, p. 176–332, CELEX number: 32017R0746 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council on in vitro diagnostic medical devices, /* COM/2012/0541 final - 2012/0267 (COD) */), CELEX number: 52012PC0541 
  • Original text 
  • Consolidated text 
  • Document summary 
• 2011/869/EU: Commission Decision of 20 December 2011 amending Decision 2002/364/EC on common technical specifications for in vitro diagnostic medical devices (notified under document C(2011) 9398) Text with EEA relevance, OJ L 341, 22.12.2011, p. 63–64, CELEX number: 32011D0869 
  • Original text 
• 2009/886/EC: Commission Decision of 27 November 2009 amending Decision 2002/364/EC on common technical specifications for in vitro diagnostic medical devices (notified under document C(2009) 9464) (Text with EEA relevance), OJ L 318, 4.12.2009, p. 25–40, CELEX number: 32009D0886 
  • Original text 
  • Consolidated text 
• 2002/364/EC: Commission Decision of 7 May 2002 on common technical specifications for in vitro-diagnostic medical devices (Text with EEA relevance) (notified under document number C(2002) 1344), OJ L 131, 16.5.2002, p. 17–30, CELEX number: 32002D0364 
  • Original text 
  • Consolidated text 
• Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices, OJ L 331, 7.12.1998, p. 1–37, CELEX number: 31998L0079 
  • Original text 
  • Consolidated text 
  • Document summary 
• Commission Regulation (EU) No 722/2012 of 8 August 2012 concerning particular requirements as regards the requirements laid down in Council Directives 90/385/EEC and 93/42/EEC with respect to active implantable medical devices and medical devices manufactured utilising tissues of animal origin (Text with EEA relevance), OJ L 212, 9.8.2012, p. 3–12, CELEX number: 32012R0722 
  • Original text 

Fundamental research

Discovery phase leading to Proof of concept

Pre-clinical model

Good Laboratory practices

• EMA, Question and Answer on Good Laboratory Practice (GLP) principles in relation to ATMPs, 26 January 2017

Non-clinical development (safety and efficacy studies)

• EMA, Guide on Advanced Therapy Medicinal Products- Non- clinical development flowchart and checklist, 29 November 2021
• EMA, CHMP, Guideline on non-clinical tolerance testing of medicinal products, EMA/CHMP/SWP/2145/00 Rev.1 Corr. 1, 22 October 2015
• EMA, CHMP, Guideline on repeated dose toxicity, CPMP/SWP/1042/99 Rev1 Corr, 18 March 2010
• EMA, CHMP, CVMP, Guideline on the principles of regulatory acceptance of 3Rs (replacement, reduction, refinement) testing approaches, EMA/CHMP/CVMP/JEG-3Rs/450091/2012, 15 December 2016
• EMA, CHMP, CVMP, Review and update of EMA guidelines to implement best practice with regard to 3Rs (replacement, reduction and refinement) in regulatory testing of medicinal products – report on actions taken, EMA/CHMP/CVMP/3Rs/677407/2015, 28 June 2018
• EMA, CHMP, CVMP, Guidance for individual laboratories for transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs, EMA/CHMP/CVMP/3Rs/94436/2014, 9 November 2017
• EMA, CHMP, Reflection paper providing an overview of the current regulatory testing requirements for medicinal products for human use and opportunities for implementation of the 3Rs, EMA/CHMP/CVMP/3Rs/742466/2015, 18 October 2018
• EMA, Veterinary Medicines and Product Data Management, Statement of the EMA position on the application of the 3Rs (replacement, reduction and refinement) in the regulatory testing of human and veterinary medicinal products, EMA/470807/2011, 23 September 2011
• 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
• EMA, Note for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products, EMEA/410/01 rev. 3, 29 June 2011
• EMA, Guideline on Tests on samples of biological origin, 3AB11A
• 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

Research on existing collections of samples

Biobanks

Registries

Research on new collections of samples

Manufacturing phase

Good manufacturing practices

• European Commission, Guidelines on Good Manufacturing Practices specific to ATMPs, C(2017) 7694 final, 22 November 2017

Chemistry Manufacturing Controls (CMC)

Clinical research

Clinical trial

• EMA, Guide on Advanced Therapy Medicinal Products- Clinical Developement flowchart and checklist, 29 November 2021,
• EMA, CHMP, Guideline on strategies to identify and mitigate risks for first-in-human clinical trials within investigational medicinal products EMEA/CHMP/SWP/28367/07 Rev.1, 20 July 2017
• EMA, CHMP, Guideline on repeated dose toxicity, CPMP/SWP/1042/99 Rev1 Corr, 18 March 2010
• Clinical Trial Facilitation Group, Recommendations related to contraception and pregnancy testing in clinical trials, 15 September 2014
• EMA, CHMP, Guideline on clinical trials in small populations, CHMP/EWP/83561/2005, 27 July 2006
• EMA, CPMP, Points to consider on applications with 1. Meta-analyses; 2. One pivotal study, CPMP/EWP/2330/99, 31 May 2001
• 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
• Existing clinical guidance for the studied indication(s) should be consulted:
  • Clinical efficacy and safety: general
  • Clinical efficacy and safety guidelines
• Regulation (EU) 2020/1043 of the European Parliament and of the Council of 15 July 2020 on the conduct of clinical trials with and supply of medicinal products for human use containing or consisting of genetically modified organisms intended to treat or prevent coronavirus disease (COVID-19), PE/28/2020/REV/1, OJ L 231, 17.7.2020, p. 12–16, CELEX number: 32020R1043 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council on the conduct of clinical trials with and supply of medicinal products for human use containing or consisting of genetically modified organisms intended to treat or prevent coronavirus disease, COM/2020/261 final, CELEX number: 52020PC0261) 
  • Original text 
• Commission Decision (EU) 2021/1240 of 13 July 2021 on the compliance of the EU portal and the EU database for clinical trials of medicinal products for human use with the requirements referred to in Article 82(2) of Regulation (EU) No 536/2014 of the European Parliament and of the Council (Text with EEA relevance), C/2021/5063, OJ L 275, 31.7.2021, p. 1–2, CELEX number: 32021D1240 
  • Original text 
• Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC Text with EEA relevance, OJ L 158, 27.5.2014, p. 1–76, CELEX number: 32014R0536 
  • Proposal (Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC, COM/2012/0369 final - 2012/0192 (COD), CELEX number: 52012PC0369) 
  • Original text 
  • Consolidated text 
  • Document summary 
• Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use, OJ L 121, 1.5.2001, p. 34–44, CELEX number: 32001L0020  
  • Proposal (Proposal for a European Parliament and Council Directive on the approximation of provisions laid down by law, regulation or administrative action relating to the implementation of Good Clinical Practice in the conduct of clinical trials on medicinal products for human use, COM/97/0369 final - COD 97/0197, OJ C 306, 8.10.1997, p. 9–15, CELEX number: 51997PC0369) 
  • Amended proposal (Amended proposal for a European Parliament and Council Directive on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use, COM/99/0193 final - COD 97/0197, OJ C 161, 8.6.1999, p. 5, CELEX number: 51999PC0193) 
  • Original text 
  • Consolidated text 
  • Document summary 
• Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products, OJ L 91, 9.4.2005, p. 13–19, CELEX number:  32005L0028 
  • Original text
• Q&A on complex clinical trials including ATMPs as IMPs: EC, EMA, HMA, Complex clinical trials – Questions and answers Version 2022-05-23, 23 May 2022 EMA/298712/2022

Good Clinical Practices

• European Commission, Guidelines on Good Clinical Practices specific to ATMPs, C(2019) 7140 final, 10 October 2019

Funding

• Regulation (EU) 2021/522 of the European Parliament and of the Council of 24 March 2021 establishing a Programme for the Union’s action in the field of health (‘EU4Health Programme’) for the period 2021-2027, and repealing Regulation (EU) No 282/2014, OJ L 107, 26.3.2021, pp. 1–29, CELEX number: 32021R0522 
  • Proposal 
  • Original text 

ATMP certification procedure by CAT

• EMA, CAT, Procedural advice on the certification of quality and non-clinical data for SMEs developing ATMPs, EMA/CAT/418458/2008/rev, 27 September 2016
• EMA, CAT, Guideline on the minimum quality and non-clinical data for certification of ATMPs, EMA/CAT/486831/2008/corr, 15 October 2010

Intellectual Property rights

Patentability

Early interactions with regulators

EMA- Innovation Task Force Briefing meetings

EMA- Scientific advice and Protocol Assistance

Early support from national competent authorities

• EMA, Heads of Medicines Agency, (EU innovation Network), Guidance for applicants on a pilot for Simultaneous National Scientific Advice (SNSA), 14 April 2020 Rev. 2
• EMA, Heads of Medicines Agency, (EU innovation Network), Simultaneous National Scientific Advice, 24 June 2021

Parallel advices (EMA/HTA, EMA/FDA)