Quality Risk Management

Transcription

1 Safeguarding public health Quality Risk Management Challenges and opportunities Ian Thrussell Strategy and Development Team GMP Inspection, I&S Division

2 Presentation overview Current regulatory and external environment QRM fundamentals system relationships, definition, primary principles, Q9 model process, application Regulatory changes EU and UK Challenges and opportunities Summary Slide 2

3 Current regulatory and external environment Fundamental issue is patient safety availability of products of appropriate quality Perceptions: - Regulatory processes inflexible - Innovation and improvement stifled - Risk averse compliance focus with non-science or non risk-based regulations and guidance - Toleration of the status quo Slide 3

4 Current regulatory and external environment Issues still occur despite regulations, guidance, standards, training, communication, inspection and enforcement: - Serious manufacturing issues: Chiron influenza vaccine contamination - Serious control issues: recent Foot and Mouth Disease - Cross contamination issues glycerol, heparin, mix ups - Unexpected events: TGN1412 (Northwick Park incident) - Criminal activities: counterfeiting Lessons being learnt! Slide 4

5 Current regulatory and external environment EU position - GMP for medicinal products for human use based on Directive 2003/94/EC - An effective QMS is already mandated by EU GMPs and most of the accepted common elements of an effective QS are already required by EU GMP. - Risk management is implicit in the current guide. - Inspections conducted into company QSs for many years but looking at QRM processes is newer. Slide 5

6 Current regulatory and external environment EU position: - Risk concept not new: mentioned 90 times and in 20 different documents in EU GMP legislation and guidance - Unless otherwise justified concept frequently used in both GMP and Quality guidelines - Risk management use in other areas Medical devices: since early 90s, e.g. ISO Application of risk management to medical devices Pharmacovigilance: risk management plans 3 to 153 pages, used to extend knowledge on safety or change warnings/dosage/excipients, withdraw from market inspection of source plasma sites for blood products Slide 6

7 Current regulatory and external environment Pressure on cost pressures for industry and regulators - Margins / resources reduced - Drive for improved efficiency and effectiveness - Supply chains changing, more global and complex Recent initiatives: - ICH Q8, Q8R, Q9, Q10 - Better and risk-based regulation: EU Other regions and countries Slide 7

8 QRM fundamentals system relationships The Regulatory system Quality system Q10 GMP Quality Risk Management Q9 Pharmaceutical Development Q8 Existing GMP Slide 8

9 QRM fundamentals definition A systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle. Slide 9

10 QRM fundamentals - primary principles The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk Slide 10

11 QRM fundamentals Q9 model process Initiate Quality Risk Management Process Risk Assessment Risk Identification Define problem, assemble information, team and timeline Risk Analysis Risk Communication Risk Evaluation Risk Control Risk Reduction Risk Acceptance unacceptable Risk Management tools Choice of internal procedure or risk management tool - Q9 process (shown), FMEA, HACCP etc Output / Result of the Quality Risk Management Process Link to company s QS Risk Review Review Events Slide 11

12 QRM fundamentals application A structured, scientific decision-making process about risks to patients and therefore implicitly to product quality Across all stages of product lifecycle However. formality is not always necessary: - Practical knowledge and internal procedures (e.g. SOPs) will be appropriate - Define level where formal (QRM) or other processes apply - Horses for courses Slide 12

13 QRM fundamentals industry application areas Current use is largely reactive: - on sites when there are significant problems - use structure and formality to get to root cause(s) - provides guide to rank issues Evaluating a company s response when things go wrong is a major diagnostic indicator of the robustness of the organisation s systems and culture Slide 14

14 QRM fundamentals industry application areas Proactive use during: - development: selection of product / process, studies to conduct, data to be submitted in CTA / MAA, specifications in PSF - IMP/commercial: protection product / environment; choice of facility/equipment type; depth of validation of facilities/equipment, process, cleaning, IT; location / method / extent of EM; supply chain evaluation; training; change management systems; quality incidents systems Slide 15

15 QRM fundamentals Competent Authority application areas European Commission: - Better Regulation launch in simplify and improve regulatory environment - impact assessments, consultations Changes to Compilation of Community Procedures - facilitate approaches to regulatory inspections - proposes baseline inspection time on different sites - aim is to establish common ground - no conflict with QRM/Better Regulation Updates to the EU GMP Guide Chapter 1 and Annex 20 Slide 16

16 Regulatory changes EU: Variations Regulations Better regulation of pharmaceuticals: towards a simpler, clearer and more flexible framework on variations - focus on the changes having a genuine impact on quality and further reduce the overall number of variations - regulatory action classified according to relative risk - applies to Community and National Licences - design space optional but encouraged - continuous improvement encouraged - Type 1A - do and tell procedures: annual reporting or immediate notification (admin procedures) - Type 1B by default Slide 17

17 Regulatory changes UK: Hampton Report Reducing administrative burdens: effective inspection and enforcement, March 2005 Executive summary: Risk assessment should be comprehensive, and should be the basis for all regulators enforcement programmes. Proper analysis of risk directs regulators efforts at areas where it is most needed, and should enable them to reduce the administrative burden of regulation, while maintaining or even improving regulatory outcomes. Slide 18

18 Regulatory changes UK: Hampton Report Principles: - allow & encourage economic progress, intervene only when there is a clear case for protection - comprehensive risk assessment to focus resources - no inspection without a reason - provide authoritative, accessible advice - businesses not have to give unnecessary information - quickly identify businesses that persistently break regulations, face proportionate and meaningful sanctions - regulators accountable for their efficiency and effectiveness, remain independent in decisions taken Slide 19

19 Regulatory changes UK: Better Regulation Not no regulation! Wide range of UK regulators in scope Statutory Code of Practice: the Regulators' Compliance Code Legal enabler for the Hampton Principles BRE/NAO reviews of the Principles are in progress - 6 key areas: Focus on outcomes Design of regulation Advice and guidance Data requests Risk based inspections Sanctions MHRA to be reviewed during 2008 Slide 20

20 Regulatory changes UK: MHRA business plan One of seven Strategic Agency Objectives: Minimise the burden of regulation so far as is compatible with our public health role Supported by Key Target 10 to progress the Better Regulation agenda - develop and implement risk assessments for all inspection types - pursue the actions in the DH Simplification Plan - take forward Better Regulation of Medicines Initiative (BROMI) Slide 21

21 Regulatory changes UK: MLX 345 on risk-based inspection programme for good practice inspections Public consultation closed 15 Jan 08 - provides background and general approaches - starter questions invite responses - link to introduction of daily fees (MLX 344, <9 Jan 08) Process not event: - phased implementation - risk appetite in pharmaceuticals is different to many other regulated areas [FSA - the level of harm or failure which one is prepared to accept ] - consequences will directly affect the health of large number of individuals Slide 22

22 Regulatory changes UK: MLX 345 on risk-based inspection programme for good practice inspections Learning from blood component regulation - blood banks not routinely inspected - desk assessment of annual compliance reports - inspect non-compliant sites For the more compliant companies - less frequent inspections and of less scope and depth.. and vice versa! Current risk assessment focuses on high risk sites and inspection frequency Slide 23

23 Regulatory changes UK: MLX 345 Model for risk assessment and inspection planning Knowledge, Intelligence about site, personnel etc. INSPECTION Previous Inspection History Post Inspection Letter Regulatory Actions Intelligence Corporate Governance Corporate Compliance Statements Risk Profile Pro-forma Self Assessment Report Inspector Risk Assessment Risk Management Review Board Inspection Planning Frequency, Duration, Scope Depth and Breadth Compliance Letter to Company Chief Executive Slide 24

24 Challenges and opportunities Trust and culture change: - Clear understanding of stakeholders needs and options - Trust and openness in working and learning together - Culture change: Overcome internal conservatism and silo thinking Organisational change management resistance to change, new competencies needed Slide 25

25 Challenges and opportunities Regulatory duty to take into account all kind of companies (global companies. medium and small size, generics etc) Must be no disadvantage to those with new approaches, especially first movers, or Small and Medium Enterprises Need to clarify and share definitions and understandings to facilitate effective implementation Degree of industry comfort with the life cycle approach? e.g. inspectors may go into Development more often Slide 26

26 Challenges and opportunities Responses currently undergoing analysis responses were received. General agreement that agreed that regulatory inspection requirements should be based on risk to public health and that non compliant organisations should carry a greater inspection burden. Further guidance is being developed and will be issued on the risk assessment process and how its three key elements of compliance history and inspection intelligence, corporate compliance statement and self-assessment reports will be performed. Slide 27

27 Challenges and opportunities The MHRA intends to work with the Industry to evaluate these processes. A pilot of is planned to commence in the 2 nd Quarter of A dialogue will be maintained with stakeholders through seminars, consultative committees, stakeholder meetings, and individual meetings with targeted groups. Slide 28

28 Conclusion MHRA: Committed to safeguarding public health but with an appropriate level of flexibility. Successful implementation requires: - effective and robust QRM underpinned by an effective QS - trust and culture change Committed to fostering innovation: new products, new ways of working, product availability Pleased to be consulted and to support initiatives Regulators also have finite resources - not possible to go further or faster without them! Slide 29

29 Abbreviations QRM: Quality Risk Management Q8: ICH draft guideline - Pharmaceutical Development, Quality by Design Q9 ICH draft guideline - QRM Q10 ICH draft guideline - pharmaceutical quality system QS Quality Systems CAPA Corrective and preventive action EM Environmental monitoring IMP Investigational Medicinal Product PSF Product Specification File CTA Clinical Trial Authorisation MAA Marketing Authorisation Application Slide 31

30 Crown copyright 2007 The materials featured within this MHRA presentation are subject to Crown copyright protection. Any other copy or use of Crown copyright materials featured in this presentation, in any form or medium, is subject to prior approval of the MHRA which has Delegated Authority from Her Majesty's Stationery Office (HMSO) to administer Crown copyright for MHRA originated material. Applications should be in writing, clearly stating the proposed use/reuse of the information, and should be sent to the MHRA at the following address: Conference and Education Function, 16 th Floor, MHRA, 1 Nine Elms Lane, London SW8 5NQ. Fax or e- mail speakers@mhra.gsi.gov.uk. You may not sell or resell any information reproduced to any third party without prior agreement. The permission to reproduce Crown copyright protected material does not extend to any material in this pack which is subject to a separate licence or is the copyright of a third party. Authorisation to reproduce such material must be obtained from the copyright holders concerned. Slide 32