Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 A... (32014R0536)
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
- 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)
- CHAPTER I
- GENERAL PROVISIONS
- Article 1
- Scope
- Article 2
- Definitions
- Article 3
- General principle
- CHAPTER II
- AUTHORISATION PROCEDURE FOR A CLINICAL TRIAL
- Article 4
- Prior authorisation
- Article 5
- Submission of an application
- Article 6
- Assessment report — Aspects covered by Part I
- Article 7
- Assessment report — Aspects covered by Part II
- Article 8
- Decision on the clinical trial
- Article 9
- Persons assessing the application
- Article 10
- Specific considerations for vulnerable populations
- Article 11
- Submission and assessment of applications limited to aspects covered by Part I or Part II of the assessment report
- Article 12
- Withdrawal
- Article 13
- Resubmission
- Article 14
- Subsequent addition of a Member State concerned
- CHAPTER III
- AUTHORISATION PROCEDURE FOR A SUBSTANTIAL MODIFICATION OF A CLINICAL TRIAL
- Article 15
- General principles
- Article 16
- Submission of application
- Article 17
- Validation of an application for the authorisation of a substantial modification of an aspect covered by Part I of the assessment report
- Article 18
- Assessment of a substantial modification of an aspect covered by Part I of the assessment report
- Article 19
- Decision on the substantial modification of an aspect covered by Part I of the assessment report
- Article 20
- Validation, assessment and decision regarding a substantial modification of an aspect covered by Part II of the assessment report
- Article 21
- Substantial modification of aspects covered by Parts I and II of the assessment report
- Article 22
- Assessment of a substantial modification of aspects covered by Parts I and II of the assessment report — Assessment of the aspects covered by Part II of the assessment report
- Article 23
- Decision on the substantial modification of aspects covered by Parts I and II of the assessment report
- Article 24
- Persons assessing the application for a substantial modification
- CHAPTER IV
- APPLICATION DOSSIER
- Article 25
- Data submitted in the application dossier
- Article 26
- Language requirements
- Article 27
- Update by way of delegated acts
- CHAPTER V
- PROTECTION OF SUBJECTS AND INFORMED CONSENT
- Article 28
- General rules
- Article 29
- Informed consent
- Article 30
- Informed consent in cluster trials
- Article 31
- Clinical trials on incapacitated subjects
- Article 32
- Clinical trials on minors
- Article 33
- Clinical trials on pregnant or breastfeeding women
- Article 34
- Additional national measures
- Article 35
- Clinical trials in emergency situations
- CHAPTER VI
- START, END, TEMPORARY HALT, AND EARLY TERMINATION OF A CLINICAL TRIAL
- Article 36
- Notification of the start of a clinical trial and of the end of the recruitment of subjects
- Article 37
- End of a clinical trial, temporary halt and early termination of a clinical trial and submission of the results
- Article 38
- Temporary halt or early termination by the sponsor for reasons of subject safety
- Article 39
- Update of the contents of the summary of results and summary for laypersons
- CHAPTER VII
- SAFETY REPORTING IN THE CONTEXT OF A CLINICAL TRIAL
- Article 40
- Electronic database for safety reporting
- Article 41
- Reporting of adverse events and serious adverse events by the investigator to the sponsor
- Article 42
- Reporting of suspected unexpected serious adverse reactions by the sponsor to the Agency
- Article 43
- Annual reporting by the sponsor to the Agency
- Article 44
- Assessment by Member States
- Article 45
- Technical aspects
- Article 46
- Reporting with regard to auxiliary medicinal products
- CHAPTER VIII
- CONDUCT OF A CLINICAL TRIAL, SUPERVISION BY THE SPONSOR, TRAINING AND EXPERIENCE, AUXILIARY MEDICINAL PRODUCTS
- Article 47
- Compliance with the protocol and good clinical practice
- Article 48
- Monitoring
- Article 49
- Suitability of individuals involved in conducting the clinical trial
- Article 50
- Suitability of clinical trial sites
- Article 51
- Traceability, storage, return and destruction of investigational medicinal products
- Article 52
- Reporting of serious breaches
- Article 53
- Other reporting obligations relevant for subject safety
- Article 54
- Urgent safety measures
- Article 55
- Investigator's brochure
- Article 56
- Recording, processing, handling and storage of information
- Article 57
- Clinical trial master file
- Article 58
- Archiving of the clinical trial master file
- Article 59
- Auxiliary medicinal products
- CHAPTER IX
- MANUFACTURING AND IMPORT OF INVESTIGATIONAL MEDICINAL PRODUCTS AND AUXILIARY MEDICINAL PRODUCTS
- Article 60
- Scope of this Chapter
- Article 61
- Authorisation of manufacturing and import
- Article 62
- Responsibilities of the qualified person
- Article 63
- Manufacturing and import
- Article 64
- Modification of authorised investigational medicinal products
- Article 65
- Manufacturing of auxiliary medicinal products
- CHAPTER X
- LABELLING
- Article 66
- Unauthorised investigational and unauthorised auxiliary medicinal products
- Article 67
- Authorised investigational and authorised auxiliary medicinal products
- Article 68
- Radiopharmaceuticals used as investigational medicinal products or as auxiliary medicinal products for a medical diagnosis
- Article 69
- Language
- Article 70
- Delegated act
- CHAPTER XI
- SPONSOR AND INVESTIGATOR
- Article 71
- Sponsor
- Article 72
- Co-sponsorship
- Article 73
- Principal investigator
- Article 74
- Legal representative of the sponsor in the Union
- Article 75
- Liability
- CHAPTER XII
- DAMAGE COMPENSATION
- Article 76
- Damage compensation
- CHAPTER XIII
- SUPERVISION BY MEMBER STATES, UNION INSPECTIONS AND CONTROLS
- Article 77
- Corrective measures to be taken by Member States
- Article 78
- Member State inspections
- Article 79
- Union controls
- CHAPTER XIV
- IT INFRASTRUCTURE
- Article 80
- EU portal
- Article 81
- EU database
- Article 82
- Functionality of the EU portal and the EU database
- CHAPTER XV
- COOPERATION BETWEEN MEMBER STATES
- Article 83
- National contact points
- Article 84
- Support by the Agency and the Commission
- Article 85
- Clinical Trials Coordination and Advisory Group
- CHAPTER XVI
- FEES
- Article 86
- General principle
- Article 87
- One payment per activity per Member State
- CHAPTER XVII
- IMPLEMENTING ACTS AND DELEGATED ACTS
- Article 88
- Committee procedure
- Article 89
- Exercise of the delegation
- CHAPTER XVIII
- MISCELLANEOUS PROVISIONS
- Article 90
- Specific requirements for special groups of medicinal products
- Article 91
- Relation with other Union legislation
- Article 92
- Investigational medicinal products, other products and procedures, free of charge for the subject
- Article 93
- Data protection
- Article 94
- Penalties
- Article 95
- Civil and criminal liability
- CHAPTER XIX
- FINAL PROVISIONS
- Article 96
- Repeal
- Article 97
- Review
- Article 98
- Transitional provision
- Article 99
- Entry into force
- ANNEX I
- APPLICATION DOSSIER FOR THE INITIAL APPLICATION
- A. INTRODUCTION AND GENERAL PRINCIPLES
- B. COVER LETTER
- C. EU APPLICATION FORM
- D. PROTOCOL
- E. INVESTIGATOR'S BROCHURE (IB)
- F. DOCUMENTATION RELATING TO COMPLIANCE WITH GOOD MANUFACTURING PRACTICE (GMP) FOR THE INVESTIGATIONAL MEDICINAL PRODUCT
- G. INVESTIGATIONAL MEDICINAL PRODUCT DOSSIER (IMPD)
- 1.1.
- Data relating to the investigational medicinal product
- Introduction
- Quality data
- Non-clinical pharmacology and toxicology data
- Data from previous clinical trials and human experience
- Overall risk and benefit assessment
- 1.2.
- Simplified IMPD by referring to other documentation
- Possibility of referring to the IB
- Possibility of referring to the SmPC
- 1.3.
- IMPD in cases of placebo
- H. AUXILIARY MEDICINAL PRODUCT DOSSIER
- I. SCIENTIFIC ADVICE AND PAEDIATRIC INVESTIGATION PLAN (PIP)
- J. CONTENT OF THE LABELLING OF THE INVESTIGATIONAL MEDICINAL PRODUCTS
- K. RECRUITMENT ARRANGEMENTS (INFORMATION PER MEMBER STATE CONCERNED)
- L. SUBJECT INFORMATION, INFORMED CONSENT FORM AND INFORMED CONSENT PROCEDURE (INFORMATION PER MEMBER STATE CONCERNED)
- M. SUITABILITY OF THE INVESTIGATOR (INFORMATION PER MEMBER STATE CONCERNED)
- N. SUITABILITY OF THE FACILITIES (INFORMATION PER MEMBER STATE CONCERNED)
- O. PROOF OF INSURANCE COVER OR INDEMNIFICATION (INFORMATION PER MEMBER STATE CONCERNED)
- P. FINANCIAL AND OTHER ARRANGEMENTS (INFORMATION PER MEMBER STATE CONCERNED)
- Q. PROOF OF PAYMENT OF FEE (INFORMATION PER MEMBER STATE CONCERNED)
- R. PROOF THAT DATA WILL BE PROCESSED IN COMPLIANCE WITH UNION LAW ON DATA PROTECTION
- ANNEX II
- APPLICATION DOSSIER FOR SUBSTANTIAL MODIFICATION
- A. INTRODUCTION AND GENERAL PRINCIPLES
- B. COVER LETTER
- C. MODIFICATION APPLICATION FORM
- D. DESCRIPTION OF THE MODIFICATION
- E. SUPPORTING INFORMATION
- F. UPDATE OF EU APPLICATION FORM
- G. PROOF OF PAYMENT OF FEE (INFORMATION PER MEMBER STATE CONCERNED)
- ANNEX III
- SAFETY REPORTING
- 1. REPORTING OF SERIOUS ADVERSE EVENTS BY THE INVESTIGATOR TO THE SPONSOR
- 2. REPORTING OF SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTIONS (SUSARS) BY THE SPONSOR TO THE AGENCY IN ACCORDANCE WITH ARTICLE 42
- 2.1.
- Adverse Events and Causality
- 2.2.
- Expectedness, unexpectedness and the RSI
- 2.3.
- Information for the reporting of SUSARs
- 2.4.
- Follow-up reports of SUSARs
- 2.5.
- Unblinding treatment allocation
- 3. ANNUAL SAFETY REPORTING BY THE SPONSOR
- ANNEX IV
- CONTENT OF THE SUMMARY OF THE RESULTS OF THE CLINICAL TRIAL
- A. CLINICAL TRIAL INFORMATION:
- B. SUBJECT DISPOSITION:
- C. BASELINE CHARACTERISTICS:
- D. END POINTS:
- E. ADVERSE EVENTS:
- F. ADDITIONAL INFORMATION:
- ANNEX V
- CONTENT OF THE SUMMARY OF THE RESULTS OF THE CLINICAL TRIAL FOR LAYPERSONS
- ANNEX VI
- LABELLING OF INVESTIGATIONAL MEDICINAL PRODUCTS AND AUXILIARY MEDICINAL PRODUCTS
- A. UNAUTHORISED INVESTIGATIONAL MEDICINAL PRODUCTS
- A.1.
- General rules
- A.2.
- Limited labelling of immediate packaging
- A.2.1.
- Immediate and outer packaging provided together
- A.2.2.
- Small immediate packaging
- B. UNAUTHORISED AUXILIARY MEDICINAL PRODUCTS
- C. ADDITIONAL LABELLING FOR AUTHORISED INVESTIGATIONAL MEDICINAL PRODUCTS
- D. REPLACING OF INFORMATION
- ANNEX VII
- CORRELATION TABLE
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