GLP Update and Hot Topics - s3.amazonaws.com€¦facility holds a GLP compliance statement ......
-
Upload
nguyenhuong -
Category
Documents
-
view
217 -
download
0
Transcript of GLP Update and Hot Topics - s3.amazonaws.com€¦facility holds a GLP compliance statement ......
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
OECD GLP Working Group
• Chair of WG - Japanese PMDA representative
• Vice Chair of WG - Swiss representative
• Meeting was held in April 2016.
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.
International GLP News: Mutual Acceptance of Data (MAD)
Current Adherents OECD Countries
Argentina
Brazil
India
Malaysia
South Africa
Singapore
Provisional Adherents 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
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.
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 17025.
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
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.
Regulatory Update: OECD
‘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
4 questions added to FAQ on OECD website…
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
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 2015
- 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
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
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.
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
Regulatory Update: US EPA
Letter of IntentEPA• This has been signed with the Chinese Ministry of
Agrochemicals (ICAMA) to mutually recognise each others GLP Programme
Inspection Closure LettersEPA• These must not be used in marketing as these are
not approval of a facility
MHRA GLP Update
• Organisation
• Information form StEM meeting
• 2015 GLP Inspection Information
• MHRA Symposium, Sep 2016
• MHRA Guidance Documents
Inspection, Enforcement & Standards DivisionInspectorate
Unit Manager, Inspectorate Operations
GLP/GCP/GDP
Andrew Gray
Operations Manager GCP
Jenny Martin
(maternity cover)
Operations Manager GDP
Peter Coombs
Operations Manager GDP
Phillip Neale
Senior Inspectors
Lesley Graham
Jason Wakelin-Smith*
Emma Whale*
Inspectors
Michael McGuinness
Martin Reed
Lisa Ottowell
* GCP/GLP Inspector
Senior Inspectors
Andy Fisher
Kathleen Meely
Inspectors
Mandy Budwal-Jagait
Balall Naeem
Hayley Dixey
Operations Manager
GLPMA/Labs Group
Stephen Vinter
MHRA Organisation
• Chris Gray is Operations Manager GMP, reporting to Richard Andrews, a Unit Manager, Inspectorate Operations (responsible for GMP Inspectorate and GPvP Inspectorate).
Regulatory Update: UK GLPMA
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)
Monitoring Inspections
Regulatory Update:
• Stakeholder Engagement Meeting (StEM) held 8 Sep 2016
• Covered:
- MHRA GxP document on data integrity
- International and UK GLPMA updates
- Industry questions
• 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
MHRA Regulatory Update…
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
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
UK GLPMA (2015 Inspection Metrics)
Item 2013 2014 2015
Number of deficiencies (total) 713 711 625
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)
Regulatory Update: UK GLPMA
• Focus on Bioequivalence Studies (GCP) has increased – particularly overseas inspections
• 2014 – 2016: 3 critical findings
- Clinical Sample Analysis
- QA
- Data Integrity
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
Regulatory Update: UK GLPMASign up to get up-to-date informationhttps://www.gov.uk/government/news/new-mhra-inspectorate-blog
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
MHRA GLP Symposium 2016
• MHRA GLP and GCP Laboratory Symposium 22 September 2016.
• 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
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)
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
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
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
Allows resources to target areas of high risk, and is therefore value adding
The Guidance does not mandate a risk based QA
programme!
Risk Based QA Programme
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
Regulatory Update: UK GLPMA: Guidance Documents
Draft MHRA GxP
Guidance on Data Integrity
Released in July, for
consultation by Industry
Comments deadline 31st
October, 2016
Organisation & Personnel
Identification of the individual(s) comprising Test
Facility Management
PI/SD Interaction &
Communication
Job descriptions must mention
the requirement to work to GLP
Training Records
Demonstration of Training
leading up to Roles
• QA
– Tolerance for Conduct of Facility Inspections
• If “Annual” in SOP, carried out in Q1 one year and Q4 next year, is this in compliance with SOP?
• Test item
– Expiry vs. retest dates
– Formulation stability must be assessed under GLP
• Sample Storage Conditions
– Impact assessment if storage temperature outside required range
• 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
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
RQA GLP Committee News
• GLP Discussion forum is being well used on www.therqa.com
– 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!