Generic PowerPoint Slide Master

1
Instrument Integration in Pharmaceutical
Environments Is it worth it?
Kyle McDuffie CSols Inc. Newark, DE
March , 2003
2
Fact or Fiction?

• LIMS purchases are often justified based on
  improved laboratory automation and instrument
  integration
• Most instruments in typical pharmaceutical QA /
  QC labs are integrated with the LIMS
• Recent draft FDA guidance on Part 11 means that
  we shouldnt worry about validating LIMS and
  laboratory systems anymore
• There is a business benefit to integrating
  instrumentation in the pharmaceutical laboratory
  environment
• Regulatory compliance is easier to demonstrate
  with an integrated electronic system

3
Agenda

• Who is CSols?
• Current Situation
• Obstacles to automation
• Drivers for moving forward
• CSols Case Studies
• Fact or Fiction?
• Conclusion

4
Who is CSols?

• Advanced Instrument Integration Specialists
• Solution providers (products, services and custom
  solutions)
• Specialize in automation of laboratory processes
  (Optimize testing)
• Provider of products services for
  Pharmaceutical QA and RD laboratories and
  Biotech Laboratories
• 13th year of business

5
Links for LIMS canOptimize Testing with any
Instrument to Any LIMS

• Balances
• Mettler, Sartorius, Ohaus others
• Chromatography Data Systems
• ICP
• Automated Distillation
• Plate Readers

• Viscometers
• Dissolution equipment
• Titrators
• Sulfur Analyzers
• TOC analyzers
• BOD
• Zymate
• TPW II
• Robotic systems

6
Current Situation
Todays Pharmaceutical Labs
LIMS
Instruments
Extensive Manual Intervention
7
Current Situation

• Common Analytical Techniques
• High Performance Liquid Chromatography (HPLC)
• UV-Visible Spectroscopy
• Automated Dissolution Test Equipment
• Wet chemical methodologies
• Weighing and Sample Preparation
• Laboratory Notebooks
• Plethora of paper notebooks per instrument,
  analyst, project, technique, etc
• Raw data pasted in notebooks, calculations,
  review signatures, QA review
• Manual Data Entry to LIMS
• Reporting

8
21 CFR Part 211 (Finished Pharmaceuticals)

• Each lot must be sampled and tested
• Conformance with specifications
• Specific tests required
• Dissolution
• Content Uniformity
• Assay
• Stability
• Quarantine
• Control of retesting
• Rejected lots
• Personnel Responsibilities
• Approval, rejection, review

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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

10
The Instrument Integration Process
Connect
Instruments
LIMS
Optimize
Connect
11
Historical obstacles to automation

• Instrument Integration (rarely completed as part
  of the LIMS)
• Phase II (which never happens)
• Acceptance of manual processes (because they have
  never been automated)
• Computerization of the previous paper process
• Reliance on the lab notebooks can be hard to
  break
• Limited cost pressure (quality, compliance
  stronger drivers)
• Reliance on Excel or similar applications for
  calculations
• Requirements for peer and supervisory review
  poorly handled in most instrument integration
  packages
• Support for pharmaceutical specific needs
  (dissolution, content uniformity, reporting of
  unknowns, replicate analysis, retesting) poorly
  handled in most instrument integration packages
  and LIMS

12
Historical obstacles to automation

• Contd
• Fear of the validation effort
• Lack of understanding of the benefits of
  integration
• High failure rate of LIMS projects
• Will users accept it?

13
Why move forward now?

• Business environment
• Cost of drugs under scrutiny
• Many companies have global standardization
  projects for LIMS
• Optimization of the laboratory workflow is good
  business
• Compliance Validation
• Laboratories continue to be targets for
  inspections, warning letters
• Offline calculations and transcription are
  major potential sources of error
• Better Products available
• Next generation instrument integration /
  optimization tools
• Lower cost / instrument

14
The CSols Way
Connect
Connect
LIMS
Optimize Translate between LIMS and
instruments Evaluate data quality, data review
and approval Standardize lab operations Transform
raw results into useful Information Simplify the
analysts job
Instrument
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Better Products.. Optimize!

• Translate
• One to many relationships between LIMS /
  instruments
• Map component names / methods
• Evaluate
• Specification checking, AQC, controls and
  standards, review and approval, esignatures
• Standardize
• One tool flexible and powerful enough to optimize
  testing for all instruments, all analytical
  methods, all LIMS
• Transform
• Calculations, detection limits, reporting limits,
  impurities and unknowns, replicate analysis and
  reporting of means and individuals, rounding
• Simplify
• Eliminate manual operations, external
  calculations, tools, meets Part 11 record keeping
  requirements

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CSols Case Studies

• Chromatography Data System Integration with LIMS
• Balance Integration with LIMS

17
Example 1 CDS Integration with LIMS

• Global pharmaceutical companies
• Multi-site projects
• Many users
• 100s of instruments
• Unknown number of analytical methods

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Example CDS, LIMS

• PerkinElmer Turbochrom / TotalChrom
• ThermoLabsystems Atlas
• Waters Empower / Millennium32
• ABI SQLLIMS
• Beckman-Coulter LabManager
• Agilent ChemLMS
• ThermoLabsystems SampleManager

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Case 1 Chromatography System Integration

• Interactive query of LIMS for samples needing
  analysis
• Analyst control for creation of sequences for the
  CDS to use
• Where samples placed, delete, add
• Duplicates, replicates, spikes, blanks, standards
• Seamless integration with the CDS
• Launched from within the CDS
• Integrating with the CDS, LIMS security profiles
• Additional calculations beyond that provided by
  either the CDS or LIMS
• Unknowns (totals, counts)
• Dissolution profiles
• Review and approval of data prior to posting to
  LIMS

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Example 2 Acquiring Balance Data
LIMS
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Example Applications

• Inhalers
• Ampoules
• Loss on Drying
• Sample Preparation

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Case 2 Balance Integration

• Create list of samples to test (from LIMS)
• Collect Stable Weights from Balance
• Calculations Verification
• Limit Checking
• Reporting Requirements
• Data approval and release
• Transfer data to LIMS

23
CSols Track Record (Top Pharms companies)

• Instrument Integration is Good Business
• Process data faster with fewer errors
• Demonstration of compliance is easier
• Audit Trails
• Ability to reconstruct what happened
• Validated calculations
• Users like it!

24
Fact or Fiction?

• LIMS purchases are often justified based on
  improved laboratory automation and instrument
  integration
• TRUE
• Most instruments in typical pharmaceutical QA /
  QC labs are integrated with the LIMS
• FALSE
• Recent draft FDA guidance on Part 11 means that
  we shouldnt worry about validating LIMS and
  laboratory systems anymore
• FALSE
• There is a business benefit to integrating
  instrumentation in the pharmaceutical laboratory
  environment
• TRUE
• Regulatory compliance is easier to demonstrate
  with an integrated electronic system
• TRUE

25
For More Info / Copy of Presentation

• Send an email to
• kylem_at_csols.com
• Phone
• 302-731-5290
• Booth 4048
• Other sources
• www.fda.gov
• www.pda.org
• Institute of Validation Technology
  (www.ivthome.org)