Kyle McDuffie, Vice President

Beckman User Meeting 2001

Delaware . Orlando . Holland . UK

Instrument Integration and Instrument Integration and Regulatory ComplianceRegulatory Compliance

Fact or FictionFact 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

AgendaAgenda

Brief review of cGMP requirements for laboratories

Brief review of 21 CFR Part 11 Promise of instrument

integration with LIMS Our approach Fact or Fiction Conclusion

cGMP 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

cGMP Requirements - LabscGMP 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

cGMP RequirementscGMP 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

21 CFR Part 11 Electronic Records; Electronic 21 CFR Part 11 Electronic Records; Electronic SignaturesSignatures

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

21 CFR Part 1121 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!

Promise of Instrument Integration - cGMP Promise of Instrument Integration - cGMP RequirementsRequirements

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• Minimum of 1 year post expiration of the batch

• Must be available for inspection

Promise of Instrument IntegrationPromise of Instrument Integration

Automate the laboratory workflow Prevent multiple instances of the same data Prevent manual transcription and related errors Simplify / enhance the review and approval processes

Leading to…..

Streamlined lot release Faster decision making (Quarantine, reject, re-test) Lower overall cost Better compliance / ease of demonstrating compliance

Instrument IntegrationInstrument Integration

“ … Any instrument to Beckman LIMS in any application”• Gas / liquid chromatography

(Waters Millennium32)

• Quality Control / Quality Assurance

• R&D / Drug Discovery

Unidirectional or Bi-directional• Continuous Operation (Polling)• Interactive Mode

– Setup Autosampler runs– Review results– Calculations, spec checking,

rounding, dilution– Advanced applications

Example Example

Our ApproachOur Approach

Seamless integration to LabManager• Maintain data integrity by utilizing TPO

Validation• Following GAMP recommendations for development and implementation

Audit Trail• Includes reason for change• Includes all user actions within the software

Archive and retrieve• Can reconstruct all activities from the audit trail• Includes all files to / from the LIMS / Instrument• Independent archive from LabManager for flexibility

Security• Username / password • Access control by job title• Inactivity timeout

Fact or FictionFact or Fiction

• the FDA doesn’t like file based architectures

• Closed systems are inherently better than open systems

• the vendor validated the system for me

• If I keep paper copies of the chromatograms, I’ll be fine

• 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 can’t be validated

• There is no installation or operational qualification 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

Fact or FictionFact 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

ConclusionsConclusions

Instrument Integration• Is a key part of laboratory automation

• Excellent tools are available now

• Regulatory compliance is improved

• Easier to demonstrate compliance with a computer than with paper files

Regulatory compliance• Beware the fiction, keep up to date

• Interpretations still evolving (FDA has promised additional guidance)

For More Info / Copy of PresentationFor More Info / Copy of Presentation

Send an email to• kylem@csols.com

• Phone 302-731-4686

Other sources• www.fda.gov

• www.pda.org

• Institute of Validation Technology (www.ivthome.org)