Clinical Trials Environment EU Legislation: Ausblick auf die neue Gesetzgebung für klinische Prüfungen

Transcription

1 The Future of the Regulatory Berlin, Clinical Trials Environment EU Legislation: Qualifizierungstag für Study Nurses Ausblick auf die neue Gesetzgebung für klinische Prüfungen Dr. med. Ingrid Klingmann Pharmaplex bvba, Brüssel

2 Table of Contents Introduction Key changes in the proposal Definitions Single application dossier Single portal EU Database CTA review process Ethical assessment National decision making Inclusion of additional countries Approval of amendments Safety reporting 2

3 Introduction Criticism on effects of Clinical Trials Directive (CTD) 2001/20/EC from all involved stakeholders Formal review process of the CTD impact by the European Commission Numerous workshops on possible solutions, e.g. Roadmap Initiative for Clinical Research in Europe : DG SANCO s proposal for: Regulation on clinical trials on medicinal products for human use, and repealing of Directive 2001/20/EC 3

4 Introduction Structure of the draft Regulation: Extended Explanatory Memorandum Regulation text with 19 Chapters Annex 1: Application dossier for initial application Annex 2: Application dossier for substantial modification Annex 3: Safety reporting Annex 4: IMP and AMP labelling Annex 5: Correlation table (Directive 2001/20/EC versus this Regulation) Legislative Financial Statement 4

5 It is a REGULATION Key Changes in the Proposal Single portal, single dossier Coordination of assessments in multi-national trials shifted from sponsor to competent authorities Coordinated 2-Part assessment procedure amongst Member States Role of ethics committees Single national decision via EU Portal Risk-based approach Streamlined safety reporting New indemnification provisions 5

6 Definitions: Clinical study Clinical study Investigation in humans to discover or verify the clinical, pharmacological or other pharmacodynamic effects Investigation in humans to identify any adverse reactions Investigation in humans to study pharmacokinetics 6

7 Definitions: Clinical trial Clinical trial : a clinical study which fulfills one of the following conditions: Investigational Medicinal Product (IMP) not authorised IMP not used within the label Assignment of subjects to a particular therapeutic strategy is decided in advance and does not fall within normal clinical practice of this member state Decision to prescribe the IMP is taken together with the decision to include the subject into the trial Diagnostic or monitoring procedures in addition to normal clinical practice 7

8 Definitions: Low-interventional clinical trial Clinical trial : a clinical study which fulfills all of the following conditions: IMP is authorised IMP used within the label or is a standard treatment in any of the Member States concerned The additional diagnostic or monitoring procedures do not pose more than minimal additional risk or burden to the safety of the subjects compared to normal clinical practice in any Member State concerned 8

9 Definitions: Non-interventional study : A clinical study other than a clinical trial IMP : a medicinal product which is being tested or used as reference, including placebo, in a clinical trial Authorised IMP : a medicinal product authorised in accordance with Regulation (EC) No 726/2004, or, in any Member State concerned, in accordance with Directive 2001/83/EC, irrespective of changes to the labelling of the medicinal product which is used as IMP Auxiliary medicinal product : a medicinal product used in the context of a clinical trial, but not as an IMP 9

10 Definitions: Investigator : an individual responsible for the conduct of a clinical trial at a clinical trial site Start of the clinical trial : the first act of recruitment of a potential subject, unless defined differently in the protocol End of the clinical trial : the last visit of the last subject, unless defined differently in the protocol Substantial modification : any change to any aspect of the clinical trial which is made after notification of the authorisation decision and which is likely to have an impact on the safety or rights of the subjects or on the reliability and robustness of the data generated in the clinical trial 10

11 Single Application Dossier: Introduction and General Principles Cover letter EU application form Protocol Investigator Brochure GMP compliance documents IMPD Auxiliary Medicinal Product Dossier Scientific Advice and PIP Content of IMP labelling Recruitment arrangements PIS and IC Suitability of investigators and sites Proof of insurance cover or indemnification Financial arrangements Proof of payment of fee 11

12 Single Portal EU Database The Commission shall set up and maintain a portal at Union level as a single entry point for the submission data and information relating to clinical trials in accordance with the Regulation. Data and information submitted through the EU portal shall be stored in the EU database Commission will set-up and control an EU Database of submitted information: To enable collaboration between competent authorities To enable sponsors to refer to previous submissions Publicly accessible with exception of personal data, commercially confidential data, inspection information 12

13 The EU-Portal Dossier submission (Part I + II) Assessment (Part I) Reaction on questions (Part I) E U Dossier submission (Part I) Questions in Part I Reporting Member State rms Sponsor Notification on start of the CT, End of recruitment, End of the CT Reactions on questions (Part II) P O R T A L Single decision of MS, Based on Part I und II Dossier Submission (Part II) Notifications Questions in Part II Comme nts to Part I Assessment Report (Part I) Concerned Member State cms Assessment Report (Part II) vfa AGAH-Workshop September 2012 Ruppert

14 Submission Content Application Dossier Content & Submission Part I «General» One Dossier Part II «National» Therapeutic & public health benefit aspects Risks & inconveniences for the subject Manufacturing/importation of IMPs/AMPs Labelling Investigator s brochure Informed consent Compensation/ rewarding arrangements Recruitment arrangements Data protection rules Suitability of - individuals - trial sites Damage compensation Biological samples EU Portal References: Art. 6 (Part I), Art. 7 (Part II), Annex I

15 Risk-based Approach and Impact on Assessment Timelines Assessment time (Report) of Part I Low-intervention clinical trials (LiCT) (Phase IV, PASS, PAES) Other clinical trials (Phase I III) Special Case: Advanced therapy clinical trials 10 days post validation date 25 days post validation date 30 days post validation date Reference: Art. 6 (4); PASS: Post Authorisation Safety Study; PAES: Post 15 Authorisation Efficacy Study

16 Assessment Timelines Part I Validation period: 6 days Sponsor validation response time: 6 days CA response time to additional information: 3 days (tacit) Assessment time Part I (see above) during which cms can give their comments to rms During assessment time rms can ask for additional explanations Clockstop for 10 resp. 20 days for the sponsor to provide answers Upon receipt of information CA can expand response time by 3 resp. 5 days 16

17 Assessment Timelines Part II Validation period: 6 days Sponsor validation response time: 6 days CA response time to additional information: 3 days (tacit) Assessment time Part II: 10 days During assessment time cms can ask for additional explanations Clockstop for 10 days for the sponsor to provide answers Upon receipt of information CA can expand response time by 5 days 17

18 Decision Making Outcome of Part I assessment from rms, reported to cmss and sponsor: Conduct is acceptable Conduct is acceptable but subject to compliance with specific listed conditions Conduct is not acceptable Each MS notifies the sponsor through the Portal within 10 days after the assessment date about approval, approval under condition or refusal of the CT (tacit) Only 2 reasons for refusal: Significant differences in normal clinical practice in the Member State leading to a disadvantage for the patients when participating Infringement of national legislation in CT with IMPs derived from cells 18

19 Thank you Any questions? 19