GLP Update and Hot Topics

Transcription

1 GLP Update and Hot Topics RQA Annual Conference Mark Goodwin 9 Nov 2016

2 Introduction International GLP Updates OECD including MAD Agreement EC/ EMA US FDA & US EPA UK GLP Update MHRA MHRA GLP Deficiencies 2015 Hot Topics RQA GLP Committee Activities

3 OECD GLP Working Group Chair of WG - Japanese PMDA representative Vice Chair of WG - Swiss representative Meeting was held in April 2016.

4 OECD GLP Working Group Headlines OECD FAQ Page: RQA Members are encouraged to view this page, as the FAQs are agreed by consensus across OECD. New FAQs will be reviewed at the OECD WG meeting in 2017.

5 International GLP News: Mutual Acceptance of Data (MAD) Current Adherents Provisional Adherents OECD Countries Argentina Brazil India Malaysia South Africa Singapore Thailand Argentina-MAD applies to industrial chemicals, pesticides and biocides only Thailand is likely to be evaluated in the near future Russia was striving for OECD MAD status but little progress recently China is not a provisional adherent although the OECD continues to work with China; China reps are Observers at OECD Working Party meetings

6 UK position on non-oecd GLP claims Non MAD adherent countries The UK GLPMA will not support claims of compliance for GLP studies made by facilities located in non MAD adherent countries even if the facility holds a GLP compliance statement issued by a monitoring authority from a MAD adherent country. National Regulatory Receiving Authorities The UK GLPMA advise national regulatory receiving authorities to request regulatory study audits of all studies (performed in non MAD adherent countries) that are deemed to be pivotal to an application. However it should be noted that final decision whether or not to accept or reject data rests with the regulatory receiving authority.

7 Regulatory Update: OECD OECD Series on GLP No.18 issued on 2 Sep 2016: Position Paper regarding the Relationship between the OECD GLP Principles and ISO/IEC Draft was made available for industry comment no comments from the GLP Committee review The paper explains the general (often philosophical) differences and is not a detailed comparison of the technical content

8 Regulatory Update: OECD OECD GLP Discussion Group: 3 themes QA activities QA statement content Who should sign QA statement? Audit of the QA department Access to QA reports Identification and characterisation of test items New advisory document planned to clear up a lot of uncertainty. Likely to be issued in 2017 Issues relating to advances in IT technology OECD Advisory Document No 17: Application of GLP to Computer Systems Issued 22 April 2016 and replaces OECD Monograph No 10.

9 Regulatory Update: OECD 4 questions added to FAQ on OECD website Re-opening a GLP study, post issue of the final report. Reporting requirements following the early termination of a GLP study. Method validation completion relative to initiation of a GLP study. Standards applicable to method validations

10 EC / EMA Update EMA currently considering Advanced Therapies and how they affect GLP EC GLP Group currently establishing a working agreement with the European Food Safety Authority (EFSA) regards study audits The possibility of EU developing data integrity guidance to be discussed at EU GLP working group meeting in spring 2017

11 EC / EMA Update EMA issued a document entitled "Triggers for Audits of GLP studies". Effective in March 2015 but only reached our attention in Dec It includes a checklist for Regulatory Assessors to check the GLP compliance status of the studies. - EMA might reject GLP studies conducted at facilities outside a national GLP Compliance programme or if they have not been inspected by the national GLPMA

12 Regulatory Update: US FDA FDA have a notice of proposed rule making in development for 21 CFR Part 58: Review All industry comments were reviewed Clearance Proposed draft issued in August 2016 Comment Industry given 90 days to comment Issue New (Final) Regulations expected in 2018

13 Regulatory Update: US FDA Non-GLP Data If non-glp data are included as part of a GLP submission it will be included in the scope of inspection (although not held to GLP standards) FDA have increased their scrutiny of test facility responsibility regarding the compliance status and integrity/quality of data from subcontractors. The SD needs to be assured of the quality and integrity of the data from GLP compliance test sites used on multi-site studies, including sponsor test sites.

14 Regulatory Update: US EPA Modified Inspection program has resolved any questions by OECD GLP Working party Consists of desk-top inspection but still doing mix of conventional inspections Geographical bundle of inspections to reduce travel time and costs

15 Regulatory Update: US EPA EPA Letter of Intent This has been signed with the Chinese Ministry of Agrochemicals (ICAMA) to mutually recognise each others GLP Programme EPA Inspection Closure Letters These must not be used in marketing as these are not approval of a facility

16 MHRA GLP Update Organisation Information form StEM meeting 2015 GLP Inspection Information MHRA Symposium, Sep 2016 MHRA Guidance Documents

17 Inspection, Enforcement & Standards * GCP/GLP Inspector Division Inspectorate Unit Manager, Inspectorate Operations GLP/GCP/GDP Andrew Gray Operations Manager GCP Jenny Martin (maternity cover) Operations Manager GLPMA/Labs Group Stephen Vinter Operations Manager GDP Peter Coombs Operations Manager GDP Phillip Neale Senior Inspectors Andy Fisher Kathleen Meely Inspectors Mandy Budwal-Jagait Balall Naeem Hayley Dixey Senior Inspectors Lesley Graham Jason Wakelin-Smith* Emma Whale* Inspectors Michael McGuinness Martin Reed Lisa Ottowell

18 MHRA Organisation Chris Gray is Operations Manager GMP, reporting to Richard Andrews, a Unit Manager, Inspectorate Operations (responsible for GMP Inspectorate and GPvP Inspectorate).

19 Regulatory Update: UK GLPMA Monitoring Inspections Risk-based approach now embedded based on inspection history, intelligence and other risk factors (mainly volume and nature of work) High risk facilities No change and are inspected every 12 months although there may be some flexibility for facilities with high compliance Low risk facilities May be subject to a 30 month inspection cycle (rather than 24 months)

20 Regulatory Update: Stakeholder Engagement Meeting (StEM) held 8 Sep 2016 Covered: - MHRA GxP document on data integrity - International and UK GLPMA updates - Industry questions

21 MHRA Regulatory Update BREXIT No comments on this at the moment! All statements will be dealt with at an Agency level, through the Policy Division. Remember, GLP works through OECD Agreements

22 Regulatory Update: UK GLPMA 2015 GLP Inspection Summary 48 inspections conducted (53 in 2014) 4 Critical deficiencies 28 Major deficiencies (11 study conduct, 6 QA, 6 computerised systems) 593 Deficiencies

23 Regulatory Update: UK GLPMA 2015 GLP Inspection: 4 Critical deficiencies - 1 Failure to comply with own procedures - 2 Study Management - 1 Multi-site aspects General comments High impact of critical findings Increased inspection findings related to data and computerised systems

24 UK GLPMA (2015 Inspection Metrics) Item Number of deficiencies (total) Number of critical deficiencies (% of total) 6 (0.84) 2 (0.28) 4 (0.64) Number of major deficiencies (% of total) 38 (5.3) 23 (3.2) 28 (4.5) Number of deficiencies (% of total) 669 (93.8) 686 (96.5) 593 (96.5)

25 Regulatory Update: UK GLPMA Focus on Bioequivalence Studies (GCP) has increased particularly overseas inspections : 3 critical findings - Clinical Sample Analysis - QA - Data Integrity

26 Regulatory Update: UK GLPMA Bioequivalence Studies (GCP) 17 major findings - 2 Computer Systems validation - 2 Data Integrity - 2 CRF Data / Source Data - 2 QA - 2 Quality System

27 Regulatory Update: UK GLPMA Sign up to get up-to-date information

28 Regulatory Update: UK GLPMA A number of projects to develop internal systems resulting in changes to GLP documents - Notification Form - GLP Certificate - Harmonised reports for GLP facilities and GCP laboratories

29 MHRA GLP Symposium 2016 MHRA GLP and GCP Laboratory Symposium 22 September Topics - Regulatory Compliance for Computer Systems - Data Integrity - Data Integrity hot topics and example findings from inspection - Bioanalytical, Regulatory and Inspection (hot topics) - Panel session

30 MHRA GLP Symposium 2016 Computer Systems Off the shelf risk assessment; utilise vendor validation effort Bespoke complexity will determine how much validation Raw data for any system other than simple systems, print-outs are not representative of original data (i.e. electronic data is the raw data)

31 MHRA GLP Symposium 2016 Data Integrity - Inspectors will expect the GxP Guidance to be followed on issue of the document - should at least be an implementation plan in place (timelines; gap analysis; risk assessment) - data governance and risk assessment key elements of DI - DI failures: deletion, amendment, duplication, processing, fabrication

32 MHRA GLP Symposium 2016 Bioanalytical topics - Justifiable reasons for repeat runs - SOP required covering QCs set up - SOP required covering review of internal standards performance - Justifiable reasons for rejection of standards - Integration process needs to be transparent, audit trailed, reviewed and SOP controlled

33 Regulatory Update: UK GLPMA: Guidance Documents Set up QA Programme based on documented Risk assessment Out of scope are study plan and amendments, report and facility audits Risk Based QA Programme Allows resources to target areas of high risk, and is therefore value adding The Guidance does not mandate a risk based QA programme!

34 Regulatory Update: UK GLPMA: Guidance Documents Selection and use of GLP test sites located outside the UK (issued April 2016) Expectation that test site is located in a country that is signatory to MAD and subject to periodic inspections If not, this must be stated in SD statement and no claim of GLP Compliance made for that phase of the study

35 Regulatory Update: UK GLPMA: Guidance Documents Draft MHRA GxP Guidance on Data Integrity Released in July, for consultation by Industry Comments deadline 31 st October, 2016

36 Organisation & Personnel Identification of the individual(s) comprising Test Facility Management Job descriptions must mention the requirement to work to GLP Training Records Demonstration of Training leading up to Roles PI/SD Interaction & Communication

37 QA Tolerance for Conduct of Facility Inspections Test item If Annual in SOP, carried out in Q1 one year and Q4 next year, is this in compliance with SOP? Expiry vs. retest dates Formulation stability must be assessed under GLP Sample Storage Conditions Impact assessment if storage temperature outside required range

38 Data Integrity Conflict of Interest around Computer System Administrator also the primary user / SME Valid documented reasons for repeats and for not reporting data Justification of acceptance of results if do not fully meet predefined acceptance criteria (in study records and report) Data scrutiny e.g. Gaps in acquisition times; changes in data filenames

39 RQA GLP Committee News Two new publications GLP in the Analytical Laboratory (now available) Practical Guide on the Roles and Responsibilities of the Study Director (awaiting publication) Distance learning course being developed on the Role and Responsibilities of the Study Director Number of webcasts in preparation Representation on the OECD GLP Discussion Group Review of MHRA GxP DI Guidance and review of new (proposed) FDA GLP Regulations

40 RQA GLP Committee News GLP Discussion forum is being well used on lots of postings (and answers) Please keep them coming! If you know of any activities or topics you feel the GLP Committee should be involved in then let us know we are here to support the RQA membership!

41 Thanks very much for your time.?