Qualification and validation: - an inspector s perspective. Ian Rees, Unit Manager Inspectorate Strategy

Transcription

1 Qualification and validation: - an inspector s perspective Ian Rees, Unit Manager Inspectorate Strategy

2 GMP - basics A system within an organisation (or linked organisations) to assure the quality of its products. Qualification and validation is part of that system. A system, based on QRM principles, to ensure that medicinal products are: consistently manufactured controlled to quality standards that are appropriate to their intended use (CTA / MA / product specification of MS or HE products) available when required to avoid shortages As simple as you can As complex as you must

3 GMP current structure Introduction Part I Part II Part III Annexes 1-17, 19, (21) 3

4 GMP future structure(?) Introduction Part I Part II Part III Annexes 1-17, 19, (21) IMPs ATIMPs / ATMPs 4

5 Annex 15 history Main EU guidance document for qualification and validation First published in 2001 and revised in 2015 by a group of EU and PIC/S experts and others. Revision driven by age of document and need to link to recent QWP guideline on process validation Revision team: UK rapporteur EU member states - Ireland, Germany, Italy and Portugal European Medicines Agency (EMA) PIC/S - Canada, US FDA 5

6 Annex 15 history/gmp revision Problem Statement Review comments, text revision Final text adopted by IWG Concept Paper Feb-May 14 Public consultation (3 or 6 months) Apr 15 Final text adopted by EC Nov 12- Feb 13 Public consultation (3 months) Review comments, text revision 1 st Oct 15 Publish, time to come into effect 6 6

7 Qualification and validation lifecycle Process Validation - new / modified / site transfers Manufacture/pack, store, transport Ongoing Process Verification New product / process / location Performance Qualification Change Control Organising & planning: stage-appropriate PQS, trained staff, QRM, VMP - Q&V policy [Engage with NCA] Operational Qualification Periodic re-evaluation Documentation: protocols, reports, 3 rd party agreements Installation Qualification (FAT) / SAT Contract(s), purchase DQ URS

8 Key changes to Annex 15 Principle and General sections Include the concept of the validation life cycle The use of risk assessments is a general expectation in the document and during the lifecycle of a medicinal product Organising and Planning section Validation is performed by suitably trained personnel but quality oversight is required The use of risk assessments for validation should be defined in detail, they are dynamic and change. 8

9 Key changes to Annex 15 Documentation including VMP section Links documentation to knowledge management Emphasises the role of deviations Need well founded, justified conclusions against pre-defined acceptance criteria in reports Qualification stages for equipment, facilities, utilities and systems section Clarifies what qualification applies to includes guidance on URS, FAT/SAT 9

10 Key changes to Annex 15 Process Validation General documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes Concurrent validation - allowed in exceptional circumstances, strong risk benefit to the patient, make visible in VMP Retrospective validation - removed Scope includes all dosage forms, new, modified processes and site transfers Includes traditional and Continuous verification approach to process validation 10

11 Key changes to Annex 15 Process Validation General Promotes involvement of production staff in validation work Requires knowledge from product development to be available for commercial manufacturing sites Where validation batches are to be released - define up front as part of a planned process. 11

12 Key changes to Annex 15 Process Validation Traditional approach A series of batches are made to confirm reproducibility. The number of batches required should be based on QRM principles and should be justified. However, the guide still quotes the number 3, without prejudice, to avoid too much confusion In general - more variability / uncertainty / complexity in the process the greater the number of validation batches required 12

13 Key changes to Annex 15 Continuous process verification (CPV) An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. (ICH Q8) Based on: an enhanced approach to development or a substantial amount of product and process knowledge and understanding, gained through historical data and manufacturing experience 13

14 Key changes to Annex 15 Hybrid approach A hybrid approach could be used for products which were validated using the traditional approach but where a lot of process knowledge has been built up over many years allowing a CPV approach. 14

15 Key changes to Annex 15 Ongoing process verification Documented evidence that the process remains in a state of control during commercial manufacture Replaced continued to ongoing process verification to avoid confusion. Applies to all (traditional, CPV, hybrid) approaches. A monitoring process to: confirm control is maintained across the product s lifecycle detect unplanned departures or unintended process variability from the process as designed 15

16 Key changes to Annex 15 Ongoing process verification Could be performed: in conjunction with the annual Product Quality Review (PQR) according to a protocol and a report, e.g. for a new product where a PQR has not yet been written or after changes to products where trends are noted. Should be more frequent for new products where process knowledge is limited. The extent and frequency should be reviewed periodically 16

17 Where can it go wrong? Links not made between documents in complex projects Forget the basic elements of any experiment: objective, method, acceptance criteria, results, conclusion Changing acceptance criteria during execution of the protocol with no / insufficient justification No checks of data in the report against the raw data resulting in anomalies which question the report s integrity 17

18 Where can it go wrong? Confusion between PQ of equipment / utilities / systems and process validation. Risk assessments: start with preconceived ideas of the end result not reviewed / updated on frequent basis Validation protocols don t include additional sampling other than normal IPC checks. Deviations only recorded in protocols and not in the formal deviation system so cannot be used in future investigations 18

19 Proportionate approach to risk?

20 Early engagement with MHRA! Thanks for your attention Questions? 20

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