Volume 10 of the publication “The rules governing medicinal products in the European Union” contains guidance documents applying to clinical trials.
A number of documents in Volume 10 are being revised and updated to bring them in line with the changes required by the Clinical Trials Regulation (EU) No 536/2014. Additionally, new documents were prepared to cover new aspects introduced by the same Regulation.
In order to make a distinction between documents applicable to clinical trials authorised under Directive 2001/20/EC (i.e. the current applicable documents) and documents relevant to clinical trials authorised under Regulation (EU) No 536/2014, these documents will be listed in two separate pages on the Eudralex Volume 10 website.
Until the Clinical Trials Regulation becomes applicable sponsors should follow the documents relevant to the Clinical Trials Directive.
During the transitional period, which will last for a period of 3 years starting from when the Regulation becomes applicable, both sets of documents will apply accordingly and should be referred to respectively according to the legislation under which the Clinical trial is conducted.
At the end of the transitional period all clinical trials shall be conducted under the Regulation and should follow only the set of documents applicable to the Regulation.
Although it is not mandatory, stakeholders are encouraged to take already into consideration a number of aspects that are outlined in the new or updated documents published in the page dedicated to the Clinical Trial Regulation and apply them to those clinical trials authorised under the Directive, to the extent possible and in compatibility with the legal framework of the Directive.
Set of documents applicable to clinical trials authorised under Regulation EU No 536/2014
Recommendation paper on decentralised elements in clinical trials |
| This recommendation paperSearch for available translations of the preceding link (December 2022) was created as part of the priority action 8 ‘Methodology guidances’ of the ACT EU initiative of the Heads of Medicines Agencies, the European Commission and the European Medicines Agency. |
Recommendations to sponsors on managing the impact of the war in Ukraine on clinical trials |
| The Clinical Trials Coordination Group (an HMA working group of experts in the classification, assessment and oversight of clinical trials from National Agencies) has published a set of recommendations focusing on the transfer of trial participants from centres in Ukraine to centres in the EU/EEA within the same multinational clinical trial. |
Guidance on the management of clinical trials during COVID-19 pandemic |
| Guidance documentSearch for available translations of the preceding link (UPDATED VERSION v5 – 10 February 2022) Slides of the webinar about the Guidance on the management of clinical trials during the COVID-19 pandemicSearch for available translations of the preceding link Webinar about the Guidance on the management of clinical trials during the COVID-19 pandemicSearch for available translations of the preceding link |
Chapter I – Application and application documents
- Templates documents for FORM section of the CTIS
- Template statement on compliance Regulation (EU) 2016/679: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
- Part II application document templates
- Compensation for trial participants – Template: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
- Harmonisation guidance: PDFSearch for available translations of the preceding link
- Investigator Curriculum Vitae template: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
- Declaration of interest template: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
- Site suitability form: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
- Informed consent and patient recruitment procedure template: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
- Compliance with applicable rules for biological samples: PDFSearch for available translations of the preceding link/WordSearch for available translations of the preceding link
Chapter II – Safety reporting
For more guidance on safety reporting please refer to the Q&A document on the Clinical Trials Regulation in Chapter V
Chapter III – Quality
- Guideline on the responsibilities of the sponsor with regard to handling and shipping of investigational medicinal products for human use in accordance with Good Clinical Practice and Good Manufacturing PracticeSearch for available translations of the preceding link
- Template for the qualified person’s declaration equivalence to EU GMP for Investigational Medicinal Products manufactured in third countries : PDF versionSearch for available translations of the preceding link – Word versionSearch for available translations of the preceding link (may 2013)
- Detailed Commission guideline of 8 December 2017 on the good manufacturing practice for investigational medicinal products pursuant to the second paragraph of the Article 63(1) of Regulation (EU) No 536/2014Search for available translations of the preceding link
- Template for IMP batch release (applicable as from the date of entry into application of Regulation (EU) No 536/2014 on Clinical Trials)Search for available translations of the preceding link
- Union Basic Format for Manufacturer’s Authorisation (June 2013)
- Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials (revision 2 – January 2022)Search for available translations of the preceding link
- Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials (Revision 2 – January 2022)Search for available translations of the preceding link
- Auxiliary medicinal products in clinical trialsSearch for available translations of the preceding link (rev. 2, June 2017)
Chapter IV – Inspections
- Guidance for the conduct of good clinical practice inspections (August 2017)Search for available translations of the preceding link
- Annex I – to guidance for the conduct of good clinical practice inspections – investigator site (September 2017)Search for available translations of the preceding link
- Annex II – to guidance for the conduct of good clinical practice inspections – clinical laboratories (August 2017)Search for available translations of the preceding link
- Annex III – to guidance for the conduct of good clinical practice inspections – computer systems (March 2018)Search for available translations of the preceding link
- Annex IV – to guidance for the conduct of good clinical practice inspections – sponsor and CRO (August 2017)Search for available translations of the preceding link
- Annex VI – to guidance for the conduct of good clinical practice inspections – record keeping and archiving of documents (June 2017)Search for available translations of the preceding link
- Annex VII – to guidance for the conduct of good clinical practice inspections – bioanalytical part, pharmacokinetic and statistical analyses of bioequivalence trials (June 2017)Search for available translations of the preceding link
- Guidance for the preparation of good clinical practice inspections (August 2017)Search for available translations of the preceding link
- Guidance for the preparation of GCP inspection reports and communication of inspection findings (February 2022)Search for available translations of the preceding link
- Guidance for coordination of GCP inspections requested in the context of marketing authorisation applications for mutual recognition and decentralised procedures and cooperation between Member States (March 2018)Search for available translations of the preceding link
- Annex V – to guidance for the conduct of good clinical practice inspections – Phase I unitSearch for available translations of the preceding link
Chapter V – Additional documents
- Guideline on reporting serious breachesSearch for available translations of the preceding link
- Appendix III b – Information to be submitted with a notification of a serious breachSearch for available translations of the preceding link
- Accelerating clinical trials in the EU (ACT EU) – Delivering an EU clinical trials transformation initiativeSearch for available translations of the preceding link
- Questions and Answers Document – Regulation (EU) 536/2014Search for available translations of the preceding link
Please note that certain Q&As and a section of this document are still being discussed within the expert group on clinical trials and are therefore not yet included. Updated versions of the document will be published progressively. - Q&A on Complex clinical trials (May 2022) Search for available translations of the preceding link
This document has been developed in close collaboration between the European Medicines Agency, the Clinical Trials Coordination Group and the Clinical Trial Expert Group. It was endorsed by those groups and by the ACT EU Steering Group. - Q&A on the interface between Regulation (EU) 536/2014 on clinical trials for medicinal products for human use (CTR) and Regulation (EU) 2017/746Search for available translations of the preceding link
This document has been developed and endorsed by the Medical Device Coordination Group (MDCG) and the Clinical Trial Expert Group (CTEG). - Question and Answers on the interplay between the Clinical Trials Regulation and the General Data Protection Regulation (April 2019)Search for available translations of the preceding link
This document is applicable under the Clinical Trials Regulation except for question 11 which explains the current situation under the Clinical Trials Directive. - Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products – EMEA/CHMP/SWP/28367/07 Rev. 1 (July 2017)
- Guideline for good clinical practice – ICH E6(R2) – EMA/CHMP/ICH/135/1995 (2016)
- Risk proportionate approaches in clinical trialsSearch for available translations of the preceding link (April 2017)
- Summaries of Clinical Trial Results for LaypersonsSearch for available translations of the preceding link (version 2 – February 2018)
- Good Lay Summary Practice GuidanceSearch for available translations of the preceding link
- Ethical considerations for clinical trials on medicinal products conducted with minorsSearch for available translations of the preceding link
- Detailed guidelines on good clinical practice specific to advanced therapy medicinal products – (Update currently ongoing)
- Guideline on the content, management and archiving of the clinical trial master fileSearch for available translations of the preceding link
- List of national contact pointsSearch for available translations of the preceding link
Chapter VI – Legislation
Regulation (EU) No 536/2014Search for available translations of the preceding link 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
Commission Implementing Regulation (EU) 2017/556Search for available translations of the preceding link of 24 March 2017 on detailed arrangements for the good clinical practice inspection procedures pursuant to Regulation (EU) No 536/2014 of the European Parliament and of the Council
Commission Delegated Regulation (EU) 2017/1569Search for available translations of the preceding link (for linguistic versions, click hereSearch for available translations of the preceding link) of 23 May 2017 supplementing Regulation (EU) 536/2014 of the European Parliament and of the Council by specifying principles and guidelines for good manufacturing practice for investigational medicinal products for human use and arrangements for inspections (applicable as from the date of entry into application of Regulation (EU) No 536/2014 on Clinical Trials)
Commission Implementing Regulation (EU) 2022/20Search for available translations of the preceding link of 7 January 2022 laying down rules for the application of Regulation (EU) No 536/2014 of the European Parliament and of the Council as regards setting up the rules and procedures for the cooperation of the Member States in safety assessment of clinical trials (Text with EEA relevance)
Set of documents applicable to clinical trials authorised under Directive 2001/20/EC
Joint EC/EMA/HMA technical notice to sponsors regarding continuous compliance with the EU legislation for clinical trials following the withdrawal of the United Kingdom from the EUSearch for available translations of the preceding link
General informationSearch for available translations of the preceding link (July 2006)
Chapter I – Application and application form
- Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trialSearch for available translations of the preceding link.
- Annex 1 revised : PDF versionSearch for available translations of the preceding link – Word versionSearch for available translations of the preceding link (revision 4 of November 2009 ; updated on 22 of November 2019). EudraCT Version 8.0 uses the Revision 4 dated November 2009 of the Clinical Trials Application Form (updated on November 22, 2019). For more information please refer to the EudraCT website.
- Substantial Amendment Notification Form : PDF versionSearch for available translations of the preceding link – Word versionSearch for available translations of the preceding link (revision 3 of June 2010)
- Declaration of the End of Trial Form : PDF versionSearch for available translations of the preceding link – Word versionSearch for available translations of the preceding link (revision 19 of June 2019)
- Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial on medicinal products for human useSearch for available translations of the preceding link (revision 1 of February 2006)
- Detailed guidance on the European clinical trials database (EUDRACT Database)Search for available translations of the preceding link (revision of April 2004)
Chapter II – Safety reporting
- Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use (“CT-3”)Search for available translations of the preceding link
- ICH guideline E2F – Note for guidance on development safety update reports (September 2010)
Chapter III – Quality of the investigational medicinal product
- Template for the qualified person’s declaration equivalence to EU GMP for Investigational Medicinal Products manufactured in third countries : PDF versionSearch for available translations of the preceding link – Word versionSearch for available translations of the preceding link (may 2013)
- Good manufacturing practice for investigational medicinal products
- Good manufacturing practices for manufacture of investigational medicinal productsSearch for available translations of the preceding link (February 2010)
- Detailed Commission guideline of 8 December 2017 on the good manufacturing practice for investigational medicinal products pursuant to the second paragraph of the Article 63(1) of Regulation (EU) No 536/2014Search for available translations of the preceding link (applicable as from the date of entry into application of Regulation (EU) No 536/2014 on Clinical Trials)
- Template for IMP batch release (applicable as from the date of entry into application of Regulation (EU) No 536/2014 on Clinical Trials)Search for available translations of the preceding link
- Union Basic Format for Manufacturer’s AuthorisationSearch for available translations of the preceding link (October 2014)
- Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trialsSearch for available translations of the preceding link
- Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trialsSearch for available translations of the preceding link (September 2018)
- Guidance on Investigational Medicinal Products (IMPs) and “non investigational medicinal products” (NIMPs)Search for available translations of the preceding link (rev. 1, March 2011)
Chapter IV – Inspections
- Guidance for the preparation of GCP inspectionsSearch for available translations of the preceding link (June 2008)
- Recommendation on inspection procedures for the verification of good clinical practice complianceSearch for available translations of the preceding link (July 2006)
- Guidance for the conduct of GCP inspectionsSearch for available translations of the preceding link (June 2008)
- Annex I to Guidance for the conduct of GCP inspections – Investigator siteSearch for available translations of the preceding link (June 2008)
- Annex II to Guidance for the conduct of GCP inspection – Clinical laboratoriesSearch for available translations of the preceding link (June 2008)
- Annex III to Guidance for the conduct of GCP inspections – Computer systemsSearch for available translations of the preceding link (June 2008)
- Annex IV to Guidance for the conduct of GCP inspections – Sponsor and CROSearch for available translations of the preceding link (June 2008)
- Annex V to Guidance for the conduct of GCP inspections – Phase I UnitsSearch for available translations of the preceding link (November 2008)
- Annex VI to Guidance for the conduct of GCP inspections – Record keeping and archiving of documentsSearch for available translations of the preceding link (March 2010)
- Annex VII to Guidance for the conduct of GCP inspections – Bioanalytical part, Pharmacokinetic and Statistical Analyses of Bioequivalence TrialsSearch for available translations of the preceding link (November 2008)
- Guidance for coordination of GCP inspections and co-operation between GCP inspectors, the reference and concerned Member States and CMD(h), in the context of the evaluation of the GCP compliance of marketing authorization applications for mutual recognition and decentralized proceduresSearch for available translations of the preceding link (June 2009)
- Guidance for exchange of GCP Inspection Reports according to Article 15(2) of Directive 2001/20/ECSearch for available translations of the preceding link (revision 1 – May 2009)
- Guidance for the communication on GCP inspections and findingsSearch for available translations of the preceding link (June 2008)
- Procedure for standardisation of GCP inspection entries in EudraCTSearch for available translations of the preceding link (November 2008)
- Guidance for the preparation of Good Clinical Practice inspection reportsSearch for available translations of the preceding link (June 2008)
- Recommendations on the qualifications of inspectors verifying compliance in clinical trials with the provisions of Good Clinical PracticeSearch for available translations of the preceding link (July 2006)
Chapter V – Additional information
- Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products – EMEA/CHMP/SWP/28367/07 Rev. 1 (July 2017)
- Guideline for good clinical practice – ICH E6(R2) – EMA/CHMP/ICH/135/1995 (2016)
- Guidelines on Good Clinical Practice specific to Advanced Therapy Medicinal ProductsSearch for available translations of the preceding link(2019)
- Guideline on the content, management and archiving of the clinical trial master fileSearch for available translations of the preceding link
- “Questions & Answers” Document – Version 11.0Search for available translations of the preceding link (May 2013)
- Ethical considerations for clinical trials on medicinal products conducted with the paediatric population:
- Guideline 2008/C168/02 on the data fields from the European clinical trials database (EudraCT) that may be included in the European database on Medicinal ProductsSearch for available translations of the preceding link
- List of fields contained in the “EudraCT” clinical trials database to be made public, in accordance with Article 57(2) of Regulation (EC) No 726/2004 and its implementing guideline 2008/C168/02Search for available translations of the preceding link (June 2019)
- Guideline 2009/C28/01 on the information concerning paediatric clinical trials to be entered into the EU Database on Clinical Trials (EudraCT) and on the information to be made public by the European Medicines Agency (EMA), in accordance with Article 41 of Regulation (EC) No 1901/2006Search for available translations of the preceding link
- List of fields to be made public from EudraCT for Paediatric Clinical Trials in accordance with Article 41 of Regulation (EC) No 1901/2006 and its implementing guideline 2009/C28/01Search for available translations of the preceding link (June 2019)
- Guidance on posting and publication of result-related information on clinical trials in relation to the implementation of Article 57(2) of Regulation (EC) No 726/2004 and Article 41(2) of Regulation (EC) No 1901/2006Search for available translations of the preceding link
- Technical guidance on the format of the data fields of result-related information on clinical trials submitted in accordance with Article 57(2) of Regulation (EC) No 726/2004 and Article 41(2) of Regulation (EC) No 1901/2006Search for available translations of the preceding link (January 2013)
- EudraCT – List of additional fields contained in EudraCT (reasons for negative opinions of the Ethics Committee)Search for available translations of the preceding link (November 2010)
Chapter VI – Legislation
- Commission Delegated Regulation (EU) 2022/2239 of 6 September 2022 amending Regulation (EU) No 536/2014 of the European Parliament and of the Council as regards labelling requirements for unauthorised investigational and unauthorised auxiliary medicinal products for human use
- 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 useSearch for available translations of the preceding link
- 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 productsSearch for available translations of the preceding link
- Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use (OJ L 262, 14.10.2003, p. 22-26)