Kyle McDuffie, Vice President

1

Part 11 Compliant Technical Solutions

• Kyle McDuffie, Vice President
• Computer and Software Validation 2002
• Delaware . Holland . UK

2
Fact or Fiction?

• the FDA is targeting laboratories in inspections
• I can buy a validated, 21 CFR Part 11 compliant
  software product
• There have been several recent warning letters
  related to laboratory systems
• Web or browser based systems are inherently more
  compliant than classic client server systems
• As long as I have the raw data, I can delete
  other electronic copies of the results
• I need to be able to re-analyze the data for the
  full retention period

3
Agenda

• Brief review of cGMP requirements for
  laboratories
• Brief review of 21 CFR Part 11
• Electronic systems
• Technology Impacts and Strategy
• Fact or Fiction?
• Conclusion

4
cGMP

• Overall FDA objectives
• Protect the public health
• Prevent fraud
• Since 1997, to assist getting lifesaving drugs to
  market faster
• FDA Inspections
• For cause
• Be able to reconstruct what occurred including
  all steps from raw materials through distribution
• Routine
• Verify compliance control

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cGMP Requirements - Labs

• FDA 21 CFR Part 211 (Finished Pharmaceuticals)
• Adequate laboratory facilities
• Each lot must be sampled and tested
• Conformance with specifications
• Specific tests required
• Dissolution
• Content Uniformity
• Assay
• Stability
• Quarantine
• Control of retesting
• Rejected lots
• Responsibilities
• Approval, rejection
• Documentation, documentation, documentation

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cGMP Requirements

• Record Keeping (211.180 through 211.198)
• Complete record of all data secured during the
  test
• Record of all calculations
• Statement of the results
• Signature or initials and date
• Second level review / approval and evidence
• Calibration records
• Method modifications records
• Record Retention
• Minimum of 1 year post expiration of the batch
• Must be available for inspection
• Can be paper or computer records

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21 CFR Part 11 Electronic Records Electronic
Signatures

• For cGMP environments
• Specifies requirements for electronic records to
  be considered equivalent to handwritten records
  for those records required by cGMP
• Key aspects
• Validation
• Audit Trail
• Security
• Authority checks
• Operational checks
• Limit access to authorized individuals
• Accountability
• Archival and retrieval

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21 CFR Part 11

• Technical Controls
• About 50 of the regulation requirements
• Primary focus of software vendors
• Procedural Controls
• About 50 of the regulation requirements
• Focused on the end-user and the environment
• Software Products
• Should provide technical functionality to allow
  the system to be operated in a compliant manner
• A vendor can not validate a system for you
• Technically compliant products can be operated in
  a non-compliant manner!

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Promise of Technical Solutions - cGMP
Requirements

• Improved Record Keeping (211.180 through
  211.198)
• Complete records
• Record of all calculations
• Electronic or printed Statement of the results
• Electronic Signature
• Electronic Second level review / approval and
  evidence
• Calibration records
• Method modifications records
• Record Retention
• Ease of retrieval / storage of records
• Minimum of 1 year post expiration of the batch
• Must be available for inspection

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Example
11
Laboratory Systems (cGMP)

• MRP / ERP
• Document Management Systems
• Chromatography Data Systems
• LIMS (Lot Release, Stability)
• Electronic Lab Notebooks
• Data Archival Solutions
• Instrument Integration
• Robotic systems

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Technology Impacts

• Wireless
• Offer promise of mobile, secure computing within
  the lab
• Improve productivity for the analyst, better lab
  automation
• Systems potentially affected
• Electronic Notebooks
• Instrument Integration (mainly balances)
• Mobile access to server based systems through a
  browser (LIMS, Document Management)
• Current state
• Products available, but low adoption rate to date
• Possible security, robustness, compliance issues
• Higher Risk

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Technology Impacts

• Web applications
• Use of the corporate intranet / sub intranet
• Offers ease of deployment, management for
  applications
• Affects
• LIMS
• MRP / ERP
• Document management systems
• Data Archival Solutions
• Instrument Integration
• Most vendors offer / plan to offer web interface
• Now mainstream, similar risk to classic client /
  server apps

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Issues for debate

• the FDA doesnt like file based architectures?
• If I validate my Excel macros, I dont need to
  keep the files, just a printer output
• Can a non compliant system be validated?
• the vendor validated the system for me
• A discrepancy between the data in the ERP, the
  LIMS and CDS is not a major problem as long as I
  can prove which one is right
• I only need to worry about new systems I put in
• Web or browser based systems cant be validated
• There is no installation or operational
  qualification on the users workstation required
  if I use a browser based system
• There is consensus within the FDA regarding the
  interpretation of all key aspects of 21 CFR Part
  11

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Strategies

• Knowledge (Regulatory, Compliance, Validation)
• Keep current
• Minimize the number of unlinked instances of the
  same GMP data through instrument integration
• Eliminate manual transcription steps
• Minimize / eliminate calculation tools like Excel
• Investigate Data Archival solutions
• Raw data
• Processed data
• LIMS data
• Adopt new technology, but do your homework first!
• Compliance is only one aspect
• Improve the workflow

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Fact or Fiction?

• the FDA is targeting laboratories in inspections
• TRUE
• I can buy a validated, 21 CFR Part 11 compliant
  software product
• FALSE
• There have been several recent warning letters
  related to laboratory systems
• TRUE
• Web or browser based systems are inherently less
  compliant than classic client server systems
• FALSE
• As long as I have the raw data, I can delete
  other electronic copies of the results
• FALSE
• I need to be able to re-analyze the data for the
  full retention period
• FALSE

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Conclusions

• Part 11 Compliant Technical Solutions in
  Laboratories
• Excellent tools are available now
• Regulatory compliance is improved
• Easier to demonstrate compliance with a computer
  than with paper files
• Emphasis needed on instrument integration, data
  archival
• Regulatory compliance
• Beware the fiction, keep up to date
• Interpretations still evolving (FDA has promised
  additional guidance beyond the 2 draft guidance
  published to date)

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For More Info / Copy of Presentation

• Send an email to
• kylem_at_csols.com
• Phone [phone]
• Other sources
• www.fda.gov
• www.pda.org
• Institute of Validation Technology
  (www.ivthome.org)