ValidationQualification of Laboratory Equipment

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• Validation/Qualification of Laboratory Equipment
• In a Regulated Environment

Mark E. Newton Assoc Quality Consultant
Equipment/ Automation/ Lab Informatics Global
Quality Laboratories Eli Lilly and Company
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Objectives

• Understand the business environment for
  laboratory equipment
• Apply risk-based thinking to Laboratory equipment
  and software
• Describe our experience with using both
  approaches to create a single laboratory standard
• Discuss opportunities for efficiency in
  implementation of either approach

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Business Environment

• Analytical equipment is purchased from a vendor
  (e.g. COTS)it is seldom customized
• Business decisions depend on integrity of
  analytical results
• Forget regulationsjust good business
• Bad results are worse than no results
• Intended use of the equipment (e.g. risk) should
  influence development activities and depth of
  each activity
• Example autoclave (sterilize product vs petri
  plates for disposal)
• Instrument and software are intertwined
  therefore, develop the package, not separate
  software/hardware
• Not true is software is custom-developed

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I Need an Approach That Is

• Holistic considers hardware and software as a
  package. I use them together!
• Consistent I need people at other sites to
  create the same package that I do
• Reasonable I dont need 50 pages for an assay
  timer and 2 pages for an HPLC
• Comprehensive I need to handle water baths to
  LIMS systems and everything between
• Actionable Leads me toward what I need to do to
  complete the job!
• Answer Do I need to help me or 1,000 employees?

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I Dont Need

• Just do everything (avoid risk)
• Dont do anything (ignore risk)
• Do what you think is right (soon becomes dont
  do anything)

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Do We Validate or Qualify?
Common we validate processes and qualify
hardware Alternate Qualification and
validation are different degrees of the same
process
Consider we qualify something that has been
validated by someone else
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Validate or Qualify?

• Be practical pick one term and go with it
• Consider your majority audience lab people like
  qualify, IT likes validate
• The term must be defined to include the whole
  instrumenthardware and software
• The term does not dictate the activities to be
  completed during implementation
• (Eli Lilly manufacturing chose qualification
  for analytical equipment practices), since labs
  are comfortable with that term

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Two Approaches AAPS and GAMP

• Both apply risk-based thinking to create
  categories for analytical equipment. Categories
  are a form of risk assessment
• Both require vendor assessments, based on risks
• Both want holistic qualification of equipment and
  associated software
• Both use DQ/IQ/OQ/PQ approach for design/testing
• Neither manages end-user software well (e.g.
  Excel applications in VBA) tend toward the do
  everything approach

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Origin of AAPS Paper

• Workshop sponsored by FIP and ISPE
• Workshop held Mar 3-5,2003
• Paper accepted for publication Jan 20, 2004
• Paper has 10 authors, representing industry,
  vendors, consultants and FDA reviewers
• Has a scientists perspective
• American Association of Pharmaceutical
  Scientists(AAPS) Qualification of Analytical
  Instruments for Use in the Pharmaceutical
  Industry A Scientific Approach AAPS
  PharmSciTech 5(1) Article 22,2004

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Quality Hierarchy in AAPS
Careful! Two ways to interpret 1. Other Q
controls cover for less qualification of
equipment 2. Qualification is the foundation on
which other Q controls are built Yes, 2 is
correct!
Q During Test
QC Checks
System Suitability Tests
Analytical Methods Validation
Q Before Test
Analytical Instrument Qualification
External Physical Standards
(My addition)
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AAPS Phases of Qualification
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AAPS IQ, OQ, PQ

• Installation Qualification assures equipment is
  placed into proper environment for success
• System Description, All components/manuals,
  Utilities/Facility/Environment, network, initial
  diagnostics
• Operational Qualification assures correct
  performance of components within the unit
• HPLC Example pump flow rate, gradient linearity,
  detector wavelength, detector linearity, oven
  temperature, retention time precision
• Calibration of components is completed prior to
  testing
• Performance Qualification assures correct
  performance of whole unit for its intended use
• Testing against use requirements
• Should bracket region of possible intended use
• Some equipment has combined OQ/PQ (e.g. pH meter)

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AAPS Roles Responsibilities(1)

• Users
• Hold ultimate responsibility for operation and
  data quality
• Should be adequately trained in instruments use
• Best qualified group to design instrument tests
  and specifications
• Quality Assurance
• Should understand qualification process
• Should learn instruments application by working
  with users
• Should review qualification process to determine
  if it meets regulatory requirements and users
  attest to scientific validity

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AAPS Roles Responsibilities(2)

• Manufacturer
• Responsible for Design Qualification
• Responsible for validating processes to
  manufacture and assemble instrument
• Responsible for validating software
• Should test assembled instrument prior to
  shipping
• Should make summary of validation efforts
  available to users
• Should provide critical functional test scripts
  to qualify instrument at user site
• Should notify users of defects discovered after
  release, offer training and support
• Discuss do you find vendors that meet these
  expectations?

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AAPS Categories Software
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AAPS Software Validation

• Firmware
• Part of instrument and requires no separate
  software activities
• For control, acquisition, processing software
• Mfg performs DQ, validates software, and provides
  validation summary to user
• User qualifies software as part of instrument
• Stand-Alone Software
• Validation administered by software developer
• Follows FDA General Principles of Software
  Validation (2002)
• User site testing is part of software development
  cycle, but does not constitute complete
  validation
• Think how to proceed when developer does not
  provide sufficient proof of validation?

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AAPS Categories Instruments
User decides where an instrument fits, based on
instrument or application (no formal criteria)
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Origin of GAMP GPG

• Product of GAMP Americas Lab Special Interest
  Group (SIG)
• Created over a 3 yr period, with 1 yr review.
• SIG was 11 people from Lab IT, consultants, GCP,
  GLP, and GMP practitioners. Review team of 30
  people, including FDA MCA inspectors.
• Has an IT perspective
• Good Automated Manufacturing Practice(GAMP)GAMP
  Good Practice Guide Validation of Laboratory
  Computerized Systems, ISPE (Publishers), 2005.

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Overview of GAMP GPG

• GAMP (Good Automated Manufacturing Practices) is
  a software and process automation group that
  operates within ISPE (International Society of
  Pharmaceutical Engineers)
• GAMP GPG categories were derived from the
  Software Categories in GAMP 4, Appendix M4
• GAMP GPG heavily relies on GAMP 4 for quality
  practices such as Risk Management, Vendor
  Evaluation and such.
• GAMP Categories are based around risk to data
  integrity, with secondary emphasis on data
  complexity
• GAMP separates the Implementation Life Cycle (for
  COTS) from the Development Life Cycle (for custom)

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GAMP GPG Categories
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GAMP Category Examples
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GAMP Activities
SILC System Implementation Life Cycle
(implement existing system) SDLC Software
Development Life Cycle (develop new system)
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GAMP Procedures
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GAMP Topics
Other sections in GAMP GPG
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SampleGAMP Security (section 14)

• For most laboratory systems, a single global
  security procedure would be sufficient
• Security should address Authentication,
  Integrity, Confidentiality, Availability
• Security Considerations (14.1)
• Verification of User Identity
• Physical Security (e.g. access to manuals,
  physical media)
• Logical Security (e.g. User accounts, user names,
  password length, password age, account lockout,
  control of accounts, timeouts, system clock,
  operating system folders and files
• Audit policies

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Remember, I Need a Standard That Is

• Holistic considers hardware and software as a
  package. I use them together!
• Consistent I need people at other sites to
  create the same package that I do
• Reasonable I dont need 50 pages for an assay
  timer and 2 pages for an HPLC
• Comprehensive I need to handle water baths to
  LIMS systems and everything between
• Actionable Leads me toward what I need to do to
  complete the job!
• Answer Do I need to help me or 1,000 employees?

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Differences AAPS

• Relies on scientist or expert to categorize not
  rule-based
• Focuses on equipment refers software to FDAs
  Principles of Software Validation
• Assumes that vendor will provide critical
  functional test scripts
• Due to brevity, some activities are inferred or
  missing
• intended use Requirements
• secure data handling Security Design Admin
• No Qualification Plan, traceability mentioned

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Differences GAMP GPG

• Focuses on equipment with microprocessor control.
  Does not address hardware only equipment
• Categories have rules and are more prescriptive.
  More categories than AAPS
• Categories do not separate hardware and software
• Activities SOPs based on categories

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Summary

• AAPS and GAMP GPG approach the same need from
  different perspectives
• AAPS focuses toward hardware
• GAMP GPG toward software
• Both use a risk-based approach to laboratory
  equipment
• Users perspective may determine which becomes
  your starting place. Help me or help 1,000
  employees?
• If starting with AAPS, additional details for
  implementation are requiredGAMP GPG provides
  missing information
• AAPS is the basis for proposed USP monograph
  Analytical Equipment Qualification lt1058gt

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References

• American Association of Pharmaceutical
  Scientists(AAPS) Qualification of Analytical
  Instruments for Use in the Pharmaceutical
  Industry A Scientific Approach AAPS
  PharmSciTech 5(1) Article 22,2004
• Good Automated Manufacturing Practice(GAMP)GAMP
  Good Practice Guide Validation of Laboratory
  Computerized Systems, ISPE (Publishers), 2005.
• Spectroscopy Focus on Quality Web page
• http//www.spectroscopymag.com/spectroscopy/articl
  e/articleList.jsp?categoryId2323
• Additional information on PQ
• Operational and Performance Qualification. LCGC
  20(4), April 2002
• Performance Qualification of LC Systems. LCGC
  20(9), September, 2002

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Contact Information

• Mark E Newton
• Eli Lilly Corporate Center
• Indianapolis, IN 46285
• Desk 317-276-0868
• Email newton_mark_e_at_lilly.com