Analytical Instrument Qualification Team A9

Chad  Briscoe,  Hidehisa  Tachiki,  Jianing  Zeng,  Manish  Yadav,  Ka9a  Pastre,  Petra  Struwe,  Ron  Shoup,  ScoA  Davis,  Michael  Blackburn,  Ping  Du

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•  Many regulations that are implicitly applicable •  Few regulations that are explicitly applicable •  Not clear which regulations apply, must pick and choose pieces

from many sources •  Not included in most (any) guidance documents for regulated Bio

(eg. FDA, EMA) •  Easy to overdo it (go GMP). Pharma needs to reduce overhead •  Easy to underdo it. Due to lack of time and/or resources •  Opinions inside companies vary as much (or more?) between

different departments in the same company than between the same departments between different companies.

Why AIQ in GBC?

Ops

QA IT

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GLP •  Swiss AGIT •  OECD Application of GLP

to Computerised Systems GMP •  USP <1058> •  GAMP5 •  FDA 21CFR Part 11 •  EMA Annex 11 •  FDA Med Device

Guidance

Some of the Regs to Consider Clinical •  FDA Guidance Comp

Systems in Clinical Investigations

•  Japanese Guideline for

Electromagnetic Records in Applications for Pharmaceuticals

Engineering •  NIST Risk Mgmt Guide

for IT systems

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Keep it in perspective In  Scope  •  Equipment  SoLware  Valida9on  •  Change  control/Rou9ne  requalifica9on  •  Instruments/Equipment  •  System  Suitability  (overview)  •  Holis9c  Approach  •  Regulatory/Audits  •  Role  of  the  Laboratory  and  IT  in  Lab  SoLware  Valida9on    Out  of  Scope  •  IT  Infrastructure  Qualifica9on  •  Design  Qualifica9on  •  Stand-­‐alone/non-­‐instrument  controlling  soLware:  spreadsheets,  

homegrown,  COTS  •  LIMS,  ELN  where  not  interfacing  with  instruments  

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•  AIQ is a globally recognized, required activity •  Most regulated labs do some form of AIQ •  Who does which activities varies greatly •  Terminology is not harmonized •  Amount of effort in companies varies greatly •  Effort should always involve: Operations, IT, QA and

Vendors

Current Situation

•  IQOQPQ •  Traditional approach still valid

•  Software validation in AIQ process •  Requalification (RQ?) •  Audits – Part 11, other regs? •  Defining the roles of Operations, QA and IT in

the process

Overview

IQ OQ PQ

At least we’re not validating that!

IQ OQ PQ in one slide! User  Requirement  Specifica9ons  

Func9onal  Specifica9ons  

Opera9onal  Qualifica9on  

Design  Specifica9on  

Design  Qualifica9on  

Installa9on  Qualifica9on  

Performance  Qualifica9on  

Process Flow

Reference

Installa'on  Qualifica'on  (IQ)  -­‐  The  IQ  is  comprised  of  documenta9on  that  demonstrates  that  the  system  is  installed  properly.      Opera'onal  Qualifica'on  (OQ)  -­‐  The  OQ  is  comprised  of  documenta9on  that  demonstrates  that  the  system  is  opera9onal  in  its  installed  environment.    Performed  by  manufacturer  Signed  off  by    owner

IQ and OQ

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•  The PQ is comprised of documentation that demonstrates that the system performs the functions that the users need it to.

•  PQ phase verifies integrity of installation at site, including network access, security, configuration tests; PQ also includes customer-specified tests that may be more relevant to the site, such as the execution of a trusted method.

•  Aspects of PQ can be holistic. eg. you might need the MS to test the HPLC acquisition.

•  Design scripts specific to the environment you are working in. •  Core validation run with curve, QCs.

•  To verify carryover, sensitivity, device communication, other instrument performance parameters.

Performance Qualification

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First Instrument •  Full IQ/OQ/PQ •  Software validation •  IT Environment set up

and check •  Functionality with anti-virus,

etc. •  Network, folder security

•  Write SOPs •  Establish maintenance

schedules

Multiple Instruments? Replicate Instrument (2nd, 3rd, etc) of same type. •  Same IQ/OQ •  Replicate IT settings •  Minimal or no PQ •  Review SOP •  Implement same PM

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Categorization Ø  For each item of incoming equipment, user/lab manager to select equipment

category and document selection rationale according to local regs, then qualify according to category.

Ø Which categorization approach? •  GAMP 5 •  USP 1058 (adapted from Bansal, et al white paper) •  Very simple

–  Tools, instruments

–  Metrology tools – reference weights, check plates (binding assays)

Ø  Categories are based on complexity, configurability, and criticality.

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•  Owner should review draft OQ carefully, remove those test scripts that simply generate busywork for vendor or CRO, and add scripts that test holistic performance.

•  Requirements not for what you buy but what you must test. •  Use requirements to build traceability matrix

•  Consider qualification of metrology tools •  Vendor should provide the specifications and any expiration dating for these

materials. From time to time, these standards will need to be re-verified. •  Calibration standards provide traceable “standard of truth” to verify or recalibrate

instruments to acceptable performance.

Random thoughts…

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Vendor Risk Analysis •  3rd party installer’s qualified •  Safety Procedures •  ISO Certificate •  Reputation Approaches •  Teleconference •  Questionnaire •  May audit on-site for major

equipment If vendor process is good, it can minimize your work.

Procurement Process •  Vendor work only isn’t

enough. Must test in your environment for your specific use.

•  General testing •  Assay specific testing

q  For most complex instruments, software can’t be validated separately from the instrument qualification.

q  Complete computerized system validation.

q What reg’s apply to electronic data? q  FDA’s 21 CFR Part 11 recognized as a global “standard” for electronic data but can’t forget other

regs that are emerging q  EMA Annex 11, GAMP5, many others?

q  Is there value in executing standard test scripts? Probably not. Only tests aspects that can change in your installation.

q  It is more value added to focus on how the instrument works in your operation with the software.

q  Validation of configured portions of the software only. q  Instrument parameters established by the software are not validatable by

end user. Example: MS source temperature, MS voltages, robotic movement details.

q  COTS code review is not necessary

Comments on Equipment Control Software Validation

Routine Maintenance System Suitability Requalification (RQ) Audits

After the IQOQPQ Process

•  Establish during or following qualification •  Define the process

•  SOP, Work Instruction, refer to Manual

•  Calibration Process •  Who to call for repair •  Archive your service contract •  Build a schedule and document it somewhere

so its not forgotten •  Give it to QA, they’ll make sure you do it.

Routine Maintenance

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Ø Establish process BEFORE release Ø Must have predefined process Ø Repair Categories

•  Move of instrument •  Upgrade •  Broken •  Routine Maintenance

Ø Requalification is what you must do before restarting the batch

Ø Often includes some elements of IQ/OQ/PQ

Requalification (RQ)

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•  Qualification of all components of an entire system at once.

•  Useful approach in many occasions

•  Repaired systems can be re-qualified holistically using a reference method.

•  Often part of PQ and RQ •  System Suitability is a common

example of holistic qualification.

Holistic Qualification

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Why? •  In GLP is usually assay specific. •  Ensure instruments and equipment are prepared for run. •  In regulated bioanalysis system suitability is the assay specific

part of the qualification process. •  Performed at regular intervals but not always for every batch Chromatographic Assays •  A few injections before, during and/or after a run Binding Assays, Plate Format •  Qualification plate specific to your assay type Details •  Specific details within other teams

Where Does System Suitability Fit In?

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Ø  Lack of consistency Ø  Regulators often don’t have consistent audit practices, some better than others Ø  May get very little notice of FDA audits so must be prepared on the IT side. Other

agencies generally give more notice. Ø  Companies in transition

Ø  Expectation for GMP testing and documentation Ø  GMP is often not necessary or appropriate.

Ø  Audits often focus more on process and documentation, not details of tests Ø  Spend extra time on documentation and ensure thorough review. Ø  Keep complete and reproducible audit trails Ø  Written procedures in place. Follow your procedures.

Ø  Printed versus electronic records: Ø  What is the definition of the raw data? Sometimes more important is what is your

companies definition. Ø  All of the data throughout the process is the raw data, not just the finalized data. Ø  Are printed versions of electronic records required?

Regulations and Audit Preparation

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IT – LAB specialist and QA •  Develop Requirements •  Manage Documentation •  Maintain Validated State throughout Lifecycle

•  Change control •  Archival and retirement

•  Software IQ/OQ and configuration •  Help Users in Acceptance testing, manage issue resolution •  Interpret and communicate regulations •  Perform Periodic Reviews Vendor •  Provide system/software installation. •  Some vendor will conduct IQ and OQ to release the equipment to

business unit. •  Ensure they follow their processes and use qualified 3rd parties. •  Obtain approval from system owner before conducting their testing.

Roles and Responsibilities 1 of 2

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Roles and Responsibilities 2 of 2 Lab •  Identify System Owner •  System/operational requirements •  Ensure proper level of validation and deliverables based risk-based

assessment. •  Work with IT to generate user acceptance tests scripts. •  Conduct user acceptance tests. •  Prepare related SOP before system release to production. •  Ensure that the validation status is maintained throughout the lifecycle of

the computerized system. •  Conduct instrument PQ •  Ensure proper training for users. •  Document calibration, maintenance, upgrades and services. •  Manage change control. General Consensus •  Business unit is the leader to ensure proper validation activities and right

functions are tested. •  QA and business project owner will sign off for software validation package •  Both IT or business unit may own the software validation/instrument

qualification.

•  Instrument Qualification is not optional •  Many good sources for an approach •  Categorization is essential •  Very difficult to separate software from

hardware testing with complex systems •  It is not necessary to over-test

•  Risk-based approach •  Test what you will use

•  AIQ is more than just IQ/OQ/PQ.

Summary

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Audit  Trail  –  Record  of  events  that  occur  during  the  use  of  a  system  that  should  include  the  9me,  date,  user  iden9fica9on,  what  occurred  and  the  reason.    Also  known  as  Log  Files  or  Trace  Files.  Calibra'on  –  Periodic  seeng  of  instrument  parameters  that  allow  instrument  to  func9on  as  intended.  Change  Control  –  Documenta9on  of  any  change  to  the  system  aLer  the  original  installa9on.    The  Change  Control  documenta9on  will  require  IQ  and  OQ  to  show  that  the  change  is  working  as  expected,  with  the  excep9on  of  a  Configura9on  Only  Change  Control.  Configura'on  Management  -­‐  Documenta9on  of  the  setup  of  the  system  for  use.    This  includes  user  roles,  privileges  and  groups  as  well  as  audit  trail  and  electronic  signature  setup  if  applicable  to  the  system.  Configura'on  Only  Change  Control  –  Documents  seeng  changes  in  the  system  soLware.    Only  OQ  documenta9on  is  required  in  addi9on  to  the  Configura9on  Only  Change  Control,  as  an  installa9on  is  not  performed.  Decommissioning  –  Removing  a  system  from  ac9ve  use.  Installa'on  Qualifica'on  (IQ)  -­‐  The  IQ  is  comprised  of  documenta9on  that  demonstrates  that  the  system  is  installed  properly.    The  extent  of  the  IQ  documenta9on  depends  on  the  type  and  complexity  of  the  system  installa9on.    The  IQ  is  performed  for  every  instrument  installa9on.  Interface  –  A  connec9on  that  allows  communica9on  between  the  soLware/computer  and  the  instrument.  Opera'onal  Qualifica'on  (OQ)  -­‐  The  OQ  is  comprised  of  documenta9on  that  demonstrates  that  the  system  is  opera9onal  in  its  installed  environment.    The  OQ  is  performed  for  every  instrument  installa9on.  Performance  Qualifica'on  (PQ)  -­‐  The  PQ  is  comprised  of  documenta9on  that  demonstrates  that  the  system  performs  the  func9ons  that  the  users  need  it  to  do  and  is  performed  only  once  per  version  of  the  soLware  used.    Also  referred  to  as  soLware  or  system  valida9on.  Remedial  Maintenance  –  Procedures  performed  on  a  system  to  correct  an  error  or  issue  with  that  system.  

Glossary 1 of 2

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Risk  Assessment  –  Procedure  used  to  determine  the  cri9cality  of  an  instrument,  which  in  turn  determines  whether  PQ  is  required.  Rou'ne  Maintenance  –  Periodic  procedures  performed  on  a  system  to  ensure  that  the  system  con9nues  to  perform  as  expected.    Includes  preventa9ve  maintenance  (PM),  verifica9on  and  calibra9on.      Script  -­‐  The  program  used  on  the  instrument  to  perform  the  needed  func9ons.    Can  be  a  General  Script  that  is  used  for  more  than  one  assay  (example:    Quality  Control  prepara9on)  or  an  Assay  Script  that  is  used  as  part  of  a  specific  analy9cal  method  for  analysis.  Standard  Opera'ng  Procedure  (SOP)  –  Document  that  describes  use  of  the  system  and  will  include  safety  concerns.    An  SOP  may  also  include  decommission  informa9on.  Test  Incident  Log  –  Document  that  lists  any  unexpected  events  that  occurred  during  the  PQ  and  how  they  were  resolved.  Test  Worksheet  –  Document  that  describes  the  purpose,  procedure  and  expected  results  of  a  PQ  test.  Traceability  Matrix  –  Charts  each  user  requirement  with  the  test  worksheets  that  test  them.  User  Requirements  –  Document  that  defines  what  func9ons  will  be  used  and  tested  as  part  of  PQ.  Valida'on  –  The  process  of  evalua9ng  a  system,  instrument,  assay  or  script  to  provide  a  high  level  of  assurance  that  they  will  perform  accurately  and  consistently  in  accordance  with  intended  user  expecta9ons.  Valida'on  Plan  –  Document  that  describes  the  system  and  how  the  system  will  be  tested.  Valida'on  Summary  –  Document  that  includes  test  results  and  statement  that  the  system  is  ready  for  use.  Verifica'on  –  Periodic  checking  of  calibra9on  parameters  to  demonstrate  that  the  instrument  is  s9ll  func9oning  as  needed.  

Glossary 2 of 2