EU Regulatory Perspective

Transcription

1 EU Regulatory Perspective Sensible Guidelines. Fergus Sweeney, Head, Compliance and Inspections, European Medicines Agency An agency of the European Union

2 Disclaimer The views presented in this presentation/these slides are those of the author and should not be understood or quoted as being made on behalf of the EMA and/or its scientific committees 2

3 Defining Quality Quality sufficient to support the decision making process on medicines throughout the clinical development and use post-marketing authorisation Collecting data, generating information, enabling decision making by: Sponsors Ethics Committees Regulators Investigators Healthcare professionals Study subjects Patients 3

4 Priority Subject rights, safety and welfare Robustness of data Identify what really matters Simplify protocol, data collection, study procedures Focus resource on what is truly important Mitigate important risks to those priorities. Risk Product of probability, impact, and detectability. How likely is it to happen, and how bad will it be if it does? Is it readily detectable? 4

5 Risk to people: Trial subjects Patients receiving authorised products Their decisions, their investigator s or physician s decisions Do I consent or not? Do I take the product or not? Why, why not? 5

6 POSSIBLE APPROACHES Trial Design and Trial Initiation Trial Conduct Data Evalution and Writing of Clinical Trial Report Regulatory Submissions and/or Publications Prioritization and risk mitigation approaches across several dimensions: Protection of trials subjects Rights, Safety, Integrity, Credibility of data and results Stratified according to knowledge of product (MA status): Medicine authorised in EU used within terms of MA or within established treatment regimen Medicine authorised in EU used significantly outside of MA, Medicine without MA in EU Customized approach depending on: Protocol complexity, extent of interventions related to trial Therapeutic indication and nature of endpoints, including population and co-medications Administration of the product, dose, formulation Complexity of study procedures and measurement, including the nature of the intervention Vulnerability of the study population 6

7 OECD Draft Recommendation on risk based approach endorsed (April 2012) work on final text in progress 7

8 CTTI 8

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10 European Science Foundation 10

11 ADAMON German initiative BfArM and academia 11

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13 Pilot launched spring 2011 Appendix 1: Guidance on risk-adapted approaches within the scope of the Clinical Trials Directive Appendix 2: Guidance on risk-proportionate approaches to the management and 13 monitoring of clinical trials (To be added following completion of the pilot phase)

14 m pdf Drug Information Association 14 ww w.di aho me. org

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18 Introduction and problem statement Purpose of the paper - facilitate the development of a more: systematic, prioritised, Proportionate, risk-based approach to quality management of clinical trials, to support the principles of GCP and to complement existing quality practices, requirements and standards. Problem can be summarised: current practices are not proportionate nor well adapted to achieving the desired goals generally very costly, resulting either in success at an unnecessarily high cost or failure which is also very costly. 18 The origins of the problem are multifactorial.

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20 Overview of Comments on Reflection Paper on risk-based quality management in clinical trials Comments from 24 stakeholders (including CRO/Sponsors/researchers associations, 4 commercial sponsors and 2 non commercial). Overall Positive approach to the researcher. Flexibility is left to the sponsors to adapt the best practices tailored for the organisation/practices. Therein lies a dilemma: The paper sets no new obligations or permissions concepts are already possible Some want more detail, more lists of what is and is not possible Others welcome open approach Need to change mindsets and preconceived ideas

21 General Comments Need for collaboration with other agencies within and outside the EU/EEA seek a common position from regulatory agencies - to avoid divergence and negative surprises during inspections and assessment: Define which risks would be acceptable for regulators so that inspections will not lead to a waterfall of findings later on. Perception of variation in what is considered as acceptable or not by the various agencies involved as well as a delay in some authorities accepting newer approaches. Concerns that auditors and inspectors themselves will not easily accept practices such as partial source data verification or remote / centralised monitoring Need for Coordination with the EU Commission and revision of legislation Paper is joint GCP IWG/CTFG text. EU regulators in close discussion with US FDA. EU legislation changing coming soon OECD, CTTI, ICH, APEC all platforms for building and ensuring consensus between regulators and with stakeholders

22 General Comments Options for pilot - phased and/or voluntary approach: This is not an obligation but a facilitation, it is already possible What about regulatory and business risk? Key is subject and patient protection and data robustness. Manage these risks well and the regulatory and business risks will be mitigated.

23 Focus more on trial protocol design and clinical implications. Quality by Design, Clinical development and Protocol design issues will be addressed- fundamental scientific aspects are addressed in other guidelines (e.g. adaptive trial designs ) Medical devices Out of scope of EMA and EU pharmaceutical legislation Sponsored trials Too much emphasis on industry sponsored clinical trials only, while more attention should be paid to academic trials Aimed at both paper will make clear

24 Encourage the use of technological advances Relevant aspects will be considered in particular in relation to quality control/monitoring/data standardisation and collection Standardise/harmonise risk based monitoring approaches put forward by EMA and FDA in order to ensure harmonisation of approaches. Good consensus between EU and US Accreditation - To manage risks not specific to any particular trial, suggest putting in place, a system of sponsor s accreditation. Concept has been raised for sponsors, institutions and investigators, and for training needs to be explored very diverse aspects need to focus. Define central monitoring Different elements of monitoring to be considered and how they can be centralised or hybridised (central and on site mixed) Is it communication, training, control, SDV, problem solving.? Will add some information but may warrant a separate Q and A.

25 Further information is required regarding the suggestion of introducing a quantitative quality assurance report within the study report. Qualitative and quantitative aspects need to be considered Some aspects already available but underutilised central data capture, data deviation, variation etc.. Linked to priorities and risks did risk mitigation work? Can this be measured? One of the more challenging aspects needs more research to define.

26 Need for standardization, protocols, data collection tools, reporting formats Standardization is an important tool but should not become a new obstacle. Initiatives already ongoing CDISC.. Examples of tolerance limits, windows.. Protocol specific and general approaches to be considered. Important concept will be better elaborated. There are also risks linked to data analysis and reporting receive too little attention. This area does need addressing Regarding the risk assessment, some scoring or risk rating method could be proposed. Risk management methodologies are well addressed elsewhere 26

27 Revise paper Next Steps Workshop with stakeholders 22 May 2012 Finalize and publish Jan 2013 Develop case studies - Establish and share experience Case Study Workshop Q Work with EU, FDA, CTTI, OECD, APEC to 27 develop concepts

28 What are you waiting for Most, if not all, that is described is already within the scope of existing legislation and guidance...change preconceived ideas, ingrained practices..technology and ideas are there.practic e is lagging behind. 28 you were doing this already. but less well planned or designed...with less focus on priorities with less understanding of risks. Why wait to do better!!!

29 Thank you questions suggestions Suggestions for next steps, case study workshops, Q and As etc to GCP@ema.europa.eu and cc: Noemie.Manent@ema.europa.eu By 20 June 2012 Subject line Risk based quality management 29