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 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
• 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