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GMP Inspections A Global Perspective Auditing of Computerised System Suppliers IPCMF & ISPE Conference Global Pharma Networks Tom Farmer 25th June 2004 – PowerPoint PPT presentation

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Title: GMP%20Inspections%20


1
GMP Inspections A Global PerspectiveAuditing
of Computerised System Suppliers
  • IPCMF ISPE Conference
  • Global Pharma NetworksTom Farmer
  • 25th June 2004

2
Overview of Presentation
  • Reasons to Audit Computerised System Suppliers
  • Outline Procedure for Audit
  • Case Studies/Examples
  • Overview of Audit Repository Centre (ARC)
  • Typical Issues/Observations
  • Summary and Conclusions

3
Reasons to Audit Suppliers
  • Business Reasons
  • Risk Management
  • Good Practice
  • Cost/Schedule/Quality Benefits
  • Regulatory
  • Requirements and Expectations

4
Business Reasons
  • Risk Assessment
  • Regulatory Impact
  • Data Integrity
  • Security
  • Product Quality
  • Business Risk
  • Risk To manufacturing/process equipment
  • Corporate Reputation
  • Safety Concerns
  • Patient Safety
  • Environmental Safety
  • Supplier Audit is not part of Risk Assessment as
    such, but an integral part of the overall Project
    Management process which includes Risk Management.

5
Business Reasons (Cont.)
  • Good Practice
  • Communication/Develop Relationships
  • Helps identify misunderstandings and risks
  • Set or clarify expectations and intentions with
    regard to documentation other deliverables
  • Identify potential gaps in procedures (eg change
    control, configuration management) at an early
    stage, so they can be addressed with minimal
    impact.
  • Cost/Schedule/Quality Benefits
  • Reduce Rework
  • On-Time Delivery
  • Aim for Right First Time

6
GMP Regulations
  • EU Vol 4 Annex 11
  • 21 CFR Part 210, 211 (Drugs)
  • 21 CFR Part 820 (Medical Devices)
  • 21 CFR Part 11 (Electronic Records Signatures)
  • ICH Q7A (Active Pharmaceutical Ingredients)

7
EU Regulations
  • EC Guide to GMP for Medicinal Products
  • Vol 4, Annex 11
  • 5. The software is a critical component of a
    computerised system. The user of such software
    should take all reasonable steps to ensure that
    it has been produced in accordance with a system
    of Quality Assurance. (emphasis supplied)

ICH
  • Q7A (API Manufacturing)
  • Not explicit regarding requirement for supplier
    audits (ie Supplier audits/assessments not
    stated as mandatory)

8
FDA Regulations
  • Do not explicitly mandate computerised system
    supplier audits, with possible exception for
    Medical Devices (21 CFR 820)
  • But note that for Medical Devices, computer
    system supplier could be providing components
    that are part of the finished product.

9
FDA Regulations (Cont.)
  • 21 CFR 820.50 (a)
  • Each manufacturer shall establish and maintain
    procedures to ensure that all purchased or
    otherwise received product and services conform
    to specified requirements. (a) Evaluation of
    suppliers, contractors, and consultants. Each
    manufacturer shall establish and maintain the
    requirements, including quality requirements,
    that must be met by suppliers, contractors, and
    consultants.
  • Each manufacturer shall
  • (1) Evaluate and select potential suppliers,
    contractors, and consultants on the basis of
    their ability to meet specified requirements,
    including quality requirements. The evaluation
    shall be documented. (emphasis supplied)
  • (2) Define the type and extent of control to be
    exercised over the product, services, suppliers,
    contractors, and consultants, based on the
    evaluation results.
  • (3) Establish and maintain records of acceptable
    suppliers, contractors, and consultants.

10
FDA Warning Letter Oct 2003
  • 4. Your firm failed to evaluate and select
    potential suppliers on the basis of their ability
    to meet specified requirements, including quality
    requirements with all evaluations documented as
    required by 21 CFR 820.50(a)(1). You failed to
    document supplier audits and your audit procedure
    (PUR-0200) fails to describe supplier audit
    procedures FDA 483, Item 7.

11
FDA Regulations
  • 21 CFR Part 11
  • Again, not explicit on supplier audits, but
    implied by the Validation and Training
    requirements
  • Need to look to FDA guidance documents

12
FDA Guidelines
  • For validation, Scope and Application guideline
    specifically references
  • FDAs guidance for industry and FDA staff General
    Principles of Software Validation (CDRH -
    Medical Device guidance)
  • GAMP 4 Guide
  • Guidance for Industry - Part 11, Electronic
    Records Electronic Signatures Scope and
    Application
  • We recommend that you base your approach on a
    justified and documented risk assessment and a
    determination of the potential of the system to
    affect product quality and safety, and record
    integrity.
  • Convergence in approach to computerised systems
    across the different regulatory groups (CDER,
    CBER, CDRH)

13
General Principles of Software Validation Final
Guidance for Industry and FDA Staff (CDRH - Jan
2002)
  • 6.3. VALIDATION OF OFF-THE-SHELF SOFTWARE AND
    AUTOMATED EQUIPMENT
  • Where possible and depending upon the device risk
    involved, the device manufacturer should consider
    auditing the vendors design and development
    methodologies (empasis supplied) used in the
    construction of the OTS software and should
    assess the development and validation
    documentation generated for the OTS software.
    Such audits can be conducted by the device
    manufacturer or by a qualified third party. The
    audit should demonstrate that the vendors
    procedures for and results of the verification
    and validation activities performed the OTS
    software are appropriate and sufficient for the
    safety and effectiveness requirements of the
    medical device to be produced using that software.

14
GAMP Guideline
  • Section 7.1 - Determining Validation Strategy
  • Suppliers should be formally assessed as part of
    the process of selecting a supplier and planning
    for validation. The decision whether to perform
    a Supplier Audit should be documented and based
    on a Risk Assessment and categorisation of the
    system components.
  • Also highlights role of end-user in assisting and
    educating suppliers
  • Appendix M2 Audit Guideline and Checklist

15
Other Industry Guidelines
  • PIC/S GOOD PRACTICES FOR COMPUTERISED SYSTEMS
    IN REGULATED GXP ENVIRONMENTS (Aug 03)
  • The assurance of the reliability of a Suppliers
    software products is attributable to the quality
    of the software engineering processes followed
    during development. This should include design,
    coding, verification testing, integration, and
    change control features of the development life
    cycle, (including after sales support). In order
    for customers to have confidence in the
    reliability of the products, they should evaluate
    the quality methodology of the supplier for the
    design, construction, supply and maintenance of
    the software.(emphasis supplied) A formal,
    extensive review of the history of the Supply
    Company and the software package may be an option
    to consider where an additional degree of
    assurance of the reliability of the software is
    needed. This should be documented in a Supplier
    Audit Report.

16
Other Industry Guidelines (Cont.)
  • PDA TR 32 Auditing of Suppliers providing
    Computer Products and Services for Regulated
    Pharmaceutical Operations
  • Includes a very detailed procedure and checklist
    for supplier audits
  • Basis of audit procedure for Audit Repository
    Centre (ARC) shared audits

17
Summary Reasons to Audit Suppliers
  • If Predicate Rules do not explicity mandate
    Supplier Audits, why conduct them?
  • Business Benefits
  • Risk Management
  • Good Practice
  • Cost/Schedule/Quality
  • Regulatory expectations
  • FDA Guidelines Requirements for System
    Validation
  • Implication of Industry Guidelines (GAMP, PIC/S,
    PDA etc)
  • Audits are not mandatory but are considered good
    practice, and it is for the regulated user to
    determine any auditing needs, scope and
    standards. Recommend that the need for supplier
    audit/assessment be linked to Risk Assessments
    (and GAMP Categorisation)

18
Summary Reasons to Audit Suppliers
  • Organisations are expected to demonstrate control
    of the processes and systems that affect data
    integrity, product quality, and patient safety
  • Quality cannot be inspected or tested into the
    finished product it needs to be designed and
    built in
  • For software, one method to help achieve this is
    to follow a formal software development lifecycle
    (SDLC).
  • Audit of suppliers helps ensure that a SDLC is in
    place and is followed.

19
Approach to Supplier Audits
20
Approach to Supplier Audits
  • Pharma Industry has not yet formally embraced a
    single standard method for supplier audit, in
    spite of regulatory expectation to evaluate
    suppliers as part of the technical acquisition
    process.
  • Possible sources
  • GAMP 4 VPCS Best Practice Guide
  • PDA TR32
  • PIC/S
  • ISO 10011 Guidelines for auditing quality systems
    Part 1 Auditing
  • Other industry guidelines
  • Have procedure/SOP in place, and ensure personnel
    are trained accordingly.

21
Approach to Supplier Audits (Cont.)
22
(No Transcript)
23
Approach to Audits - Initiation
  • Determine Need for Audit
  • Based on Risk Assessment
  • System Categorisation
  • System Scale and Complexity
  • Define appropriate Audit Type
  • Document justification for Audit (or otherwise)
  • As part of Risk Assessment and/or within
    Validation Master Plan

24
Risk Assessment (GAMP App M3)
25
GAMP Software Categorisations
26
GAMP GLP Good Practice Guide
27
Audit types
  • Postal Audits / Assessments
  • System Audit / Detailed Audit
  • Surveillance Audit / Monitoring Audit
  • Joint Audits
  • Shared Audits

28
Approach to Audits Planning
  • End User inputs
  • Risk Assessment System Categorisation
  • Supplier Audit Procedure and Standard Checklist
  • Validation Master Plan
  • System Specifications/User Requirements/Project
    Brief
  • Supplier Inputs (If available)
  • Supplier Profile
  • Organisation Chart
  • Product/Service Details
  • Development Methodology
  • Proposal/Quotation

29
Approach to Audits Planning (Cont.)
  • Preparation
  • Audit Agenda
  • Audit Specific Checklist
  • Contact Supplier
  • Agree date and timescales with Supplier
  • Copy Supplier with agenda and checklist
  • Confirm resource availability with Supplier

30
Approach to Audits - Conduct
  • Typical Agenda
  • Introductions
  • Company Overview Presentation (including Quality
    System Overview/Workflow Methodology)
  • Office/Facility Tour
  • Inspection of selected Audit Areas
  • Include QMS and Procedures, Project
    Documentation, Maintenance etc
  • Review Findings/Observations
  • Present Findings to Supplier

31
Approach to Audits Checklist/Audit Areas
  • GAMP
  • Company Overview
  • Organisation and Quality Management
  • Planning and Product/Project Management
  • Specifications
  • Implementation
  • Testing
  • Completion and Release
  • Support/Maintenance
  • Supporting Processes and Activities
  • PDA TR 32
  • Quality System
  • Project Management
  • Methodology
  • Testing
  • Configuration Management
  • Manufacturing
  • Document and Records Management
  • Security
  • Training and Education
  • Maintenance

32
Comment on use of checklists
  • Need to be careful with use of standard
    checklists
  • Key is in preparation for audit
  • Tailor audit criteria and checklist based on
    supplier product and/or services
  • Try to ensure that audit criteria is suitably
    descriptive within checklist
  • When documenting audit execution
  • Try to avoid simple yes/no type responses
  • Include comments as appropriate to elaborate on
    and explain answers and observations
  • Include objective evidence, by unambiguous
    reference, or attachment

33
Approach to Audits Observations
  • Communicate observations back to Supplier for
    response
  • Consider categorisation of observations (eg
    Critical, Major, Minor, Comment only)
  • Helps to set priorities for actions
  • Helps justification of decision
  • Highlight positives also ie where supplier
    meets or exceeds industry best practices

34
Approach to Audits Report
  • Audit Report to be issued for approval
  • Include completed checklist, not just
    observations/findings
  • Include positive observations also
  • Formal Response on observations required from
    Supplier

35
Approach to Audits Follow Up
  • Need to ensure close out of observations by
    supplier
  • Remember, past performance is a good indicator of
    future performance (but not a guarantee)
  • Continuous monitoring is important, particularly
    for larger projects and customised systems
  • Use audit as an opportunity to establish open
    dialog and collaboration with your suppliers

36
Case Studies / Examples
37
Case Study/Example 1
  • Operations identify need for new automated
    system
  • Projects Group prepare equipment specification
  • Projects Group select Vendor/Supplier
  • Main Criteria Used
  • Cost (Cheapest!)
  • Technology
  • At FAT stage, Projects Group request input from
    Quality Unit / Validation

38
Case Study/Example 1 (Cont.)
  • Assessment/Audit planned executed
  • Findings
  • No Quality Systems/Procedures in place at
    supplier
  • Poor Design Documentation (No Functional
    Specification, etc)
  • Poor Change management/configuration management
  • Planned FAT Testing of limited benefit from
    Validation perspective additional testing
    required.

39
Case Study/Example 1 (Cont.)
  • Actions
  • DQ developed and executed
  • Develop additional detailed test procedures for
    FAT, Site testing qualification
  • Impact
  • Project Schedule Impact (Project Delayed)
  • Cost Impact (Internal costs as well as Supplier)

40
Case Study / Example 2
  • Project Group include Quality Unit /Validation at
    project definition phase.
  • Postal Assessment of all prospective suppliers,
    followed by conference call with each supplier
    (ie Quality issues addressed as part of bid
    analysis, as well as technical and commercial
    issues)
  • Prefered Supplier agreed by all parties
    (Operations, Projects, Quality)

41
Case Study / Example 2 (cont.)
  • Detailed systems audit conducted in selected
    suppliers premises at start of project
  • Limited/minor issues only raised at audit
  • On-going monitoring of supplier during project,
    up to system delivery to site
  • On time, within budget no surprises

42
Case Study / Example 3
  • Replacement of Laboratory Analysers
  • Categorised as GAMP Category 3 (Standard
    Software), but systems considered GxP critical
  • Supplier Audit indicated by company SOP
  • Issues
  • Multiple Suppliers (gt 6)
  • Local Supplier location not the same as System
    Development location.

43
Case Study / Example 3 (Cont.)
  • Following consultation with end-user, decided on
    Postal Audit (GAMP VPCS Good Practice Guide used
    as template).
  • Review of responses followed up by conference
    call with supplier to clarify written replies and
    request additional information
  • Reserved right to request face-to-face detailed
    audit, if deemed necessary
  • Main Benefits - Cost Saving.
  • Also, get involvement/feedback from system
    development group, as well as local distribution
    and support groups.

44
Case Study / Example 4
  • Manufacturing Control System
  • Categorised as GAMP 4/5, and system considered
    GMP Critical
  • Challenges
  • Scale of project
  • Multiple locations involved
  • Quality Unit an integral part of project process.
  • Aim to instill a culture of Right First Time

45
Case Study / Example 4 (Cont.)
  • Supplier Audit conducted as part of selection
    process
  • Follow-up surveillance audits/reviews during
    implementation (monthly) to supplement suppliers
    internal quality group.
  • Benefits
  • Identified issues at an earlier stage, and helped
    minimise impact
  • Reduced Rework/Retesting on site
  • Helped ensure overall schedule targets met

46
Shared Audits
47
ARC (Audit Repository Centre)
  • Centralised repository for audit reports,
    available to subscribing end-user companies. Not
    strictly limited to computerised system
    suppliers.
  • Statistics (as at June 2004)
  • Audits Available 28
  • Audits Scheduled - 13
  • Audits under consideration 18
  • Links
  • http//www.auditcenter.com/available.htm
  • http//www.auditcenter.com/scheduled.htm
  • http//www.auditcenter.com/consideration.htm

48
ARC (Cont)
  • Probably more appropriate as part of corporate
    system selection, may not be fully suitable for
    local (smaller) system implementations.
  • Access to ARC report does not absolve end-user
    from responsibility need to analyse audit
    results and observations, and make decision on
    supplier acceptability.
  • For project based systems, will still require
    on-going monitoring of supplier/implementer

49
Typical Issues / Observations
50
Considerations Client side
  • Timing of Audit/Assessment
  • Scope / Intent of Audit
  • Supplier Preparation (for Audit)
  • Follow up on Audit Observations/Findings
  • Overall business benefits of Quality (and
    Operations) input at the design and procurement
    stages

51
Typical Issues Supplier Side
  • Training
  • In-House Quality Procedures
  • Regulatory Issues/GAMP/21 CFR Part 11
  • Technical Training
  • Change Control
  • Typical focus on cost and schedule impact,
    lacking definition of re-test requirements and
    traceability
  • Configuration Management
  • Uncertainty as to requirements, Procedures and
    Baselines not clearly defined

52
Summary and Conclusions
53
Summary
  • Supplier Audit does not solve all problems, and
    is not a standalone process, but is a integral
    part of the overall project management process to
    help ensure sucessful system implementation
  • Use Risk Assessment to determine need for
    Audit/Assessment
  • Focus on Business Benefits, as well as Regulatory
    Needs
  • Improve quality of delivered systems
  • Schedule Impact/Delivery to Market
  • Cost Reduction (Minimise Rework)
  • Teamwork Partnership
  • Enhance co-operation between Quality, Projects
    Operations
  • Develop relationship and Improve communication
    with supplier

54
Questions?
  • Contact Tom Farmer
  • Mobile 087-299 5454
  • tom.farmer_at_global-networksgroup.com
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