Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16…

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 · European Union · 32014R0536

830 provisions in 2126 nodes · 41 provisions hand work to national law

Defined terms · All instruments · Internet · accounting · admissibility · advertising · auditing · cartel · computer science · confidentiality

CHAPTER I GENERAL PROVISIONS

Article 1 Scope

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Article 2 Definitions

Article 3 General principle

CHAPTER II AUTHORISATION PROCEDURE FOR A CLINICAL TRIAL

Article 4 Prior authorisation

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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

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Article 10 Specific considerations for vulnerable populations

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Article 11 Submission and assessment of applications limited to aspects covered by Part I or Part II of the assessment report

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Article 12 Withdrawal

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Article 13 Resubmission

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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

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Article 16 Submission of application

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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

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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

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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

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CHAPTER IV APPLICATION DOSSIER

Article 25 Data submitted in the application dossier

Article 26 Language requirements

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Article 27 Update by way of delegated acts

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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

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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

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Article 37 End of a clinical trial, temporary halt and early termination of a clinical trial and submission of the results

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Article 38 Temporary halt or early termination by the sponsor for reasons of subject safety

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Article 39 Update of the contents of the summary of results and summary for laypersons

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CHAPTER VII SAFETY REPORTING IN THE CONTEXT OF A CLINICAL TRIAL

Article 40 Electronic database for safety reporting

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Article 41 Reporting of adverse events and serious adverse events by the investigator to the sponsor

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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

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Article 44 Assessment by Member States

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Article 45 Technical aspects

Article 46 Reporting with regard to auxiliary medicinal products

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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

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Article 48 Monitoring

Article 49 Suitability of individuals involved in conducting the clinical trial

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Article 50 Suitability of clinical trial sites

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Article 51 Traceability, storage, return and destruction of investigational medicinal products

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Article 52 Reporting of serious breaches

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Article 53 Other reporting obligations relevant for subject safety

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Article 54 Urgent safety measures

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Article 55 Investigator's brochure

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Article 56 Recording, processing, handling and storage of information

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Article 57 Clinical trial master file

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Article 58 Archiving of the clinical trial master file

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Article 59 Auxiliary medicinal products

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CHAPTER IX MANUFACTURING AND IMPORT OF INVESTIGATIONAL MEDICINAL PRODUCTS AND AUXILIARY MEDICINAL PRODUCTS

Article 60 Scope of this Chapter

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Article 61 Authorisation of manufacturing and import

Article 62 Responsibilities of the qualified person

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Article 63 Manufacturing and import

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Article 64 Modification of authorised investigational medicinal products

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Article 65 Manufacturing of auxiliary medicinal products

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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

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Article 69 Language

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Article 70 Delegated act

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CHAPTER XI SPONSOR AND INVESTIGATOR

Article 71 Sponsor

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Article 72 Co-sponsorship

Article 73 Principal investigator

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Article 74 Legal representative of the sponsor in the Union

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Article 75 Liability

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CHAPTER XII DAMAGE COMPENSATION

Article 76 Damage compensation

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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

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Article 79 Union controls

CHAPTER XIV IT INFRASTRUCTURE

Article 80 EU portal

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Article 81 EU database

Article 82 Functionality of the EU portal and the EU database

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CHAPTER XV COOPERATION BETWEEN MEMBER STATES

Article 83 National contact points

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Article 84 Support by the Agency and the Commission

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Article 85 Clinical Trials Coordination and Advisory Group

Article 86 General principle

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Article 87 One payment per activity per Member State

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CHAPTER XVII IMPLEMENTING ACTS AND DELEGATED ACTS

Article 88 Committee procedure

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Article 89 Exercise of the delegation

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CHAPTER XVIII MISCELLANEOUS PROVISIONS

Article 90 Specific requirements for special groups of medicinal products

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Article 91 Relation with other Union legislation

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Article 92 Investigational medicinal products, other products and procedures, free of charge for the subject

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Article 93 Data protection

Article 95 Civil and criminal liability

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CHAPTER XIX FINAL PROVISIONS

Article 98 Transitional provision

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Article 99 Entry into force

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Preamble

ANNEX I APPLICATION DOSSIER FOR THE INITIAL APPLICATION

A. INTRODUCTION AND GENERAL PRINCIPLES

C. EU APPLICATION FORM

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)

36.

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1.1. Data relating to the investigational medicinal product

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

50.

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Possibility of referring to the IB

51.

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Possibility of referring to the SmPC

1.3. IMPD in cases of placebo

54.

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H. AUXILIARY MEDICINAL PRODUCT DOSSIER

55.

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I. SCIENTIFIC ADVICE AND PAEDIATRIC INVESTIGATION PLAN (PIP)

J. CONTENT OF THE LABELLING OF THE INVESTIGATIONAL MEDICINAL PRODUCTS

58.

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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)

67.

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O. PROOF OF INSURANCE COVER OR INDEMNIFICATION (INFORMATION PER MEMBER STATE CONCERNED)

68.

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P. FINANCIAL AND OTHER ARRANGEMENTS (INFORMATION PER MEMBER STATE CONCERNED)

Q. PROOF OF PAYMENT OF FEE (INFORMATION PER MEMBER STATE CONCERNED)

72.

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R. PROOF THAT DATA WILL BE PROCESSED IN COMPLIANCE WITH UNION LAW ON DATA PROTECTION

73.

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ANNEX II APPLICATION DOSSIER FOR SUBSTANTIAL MODIFICATION

A. INTRODUCTION AND GENERAL PRINCIPLES

C. MODIFICATION APPLICATION FORM

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D. DESCRIPTION OF THE MODIFICATION

E. SUPPORTING INFORMATION

F. UPDATE OF EU APPLICATION FORM

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G. PROOF OF PAYMENT OF FEE (INFORMATION PER MEMBER STATE CONCERNED)

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ANNEX III SAFETY REPORTING

1. REPORTING OF SERIOUS ADVERSE EVENTS BY THE INVESTIGATOR TO THE SPONSOR

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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

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2.2. Expectedness, unexpectedness and the RSI

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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

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A. CLINICAL TRIAL INFORMATION:

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B. SUBJECT DISPOSITION:

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C. BASELINE CHARACTERISTICS:

F. ADDITIONAL INFORMATION:

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ANNEX V CONTENT OF THE SUMMARY OF THE RESULTS OF THE CLINICAL TRIAL FOR LAYPERSONS

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10.

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ANNEX VI LABELLING OF INVESTIGATIONAL MEDICINAL PRODUCTS AND AUXILIARY MEDICINAL PRODUCTS

A. UNAUTHORISED INVESTIGATIONAL MEDICINAL PRODUCTS

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

Table

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