Analytical Equipment Qualification/Validation

Overview Presentation

Steve Hancock

Pharmaceutical Development Feb 2005

Equipment Qualification
Equipment Qualification!! Another regulatory hurdle or an assurance of correctly performing equipment. Industry standard not just Pharmaceuticals

What is it? Why is it being enforced The 4 Qs Whats currently available

What is it?

Measuring and testing equipment having an effect on the accuracy or validity of tests shall be calibrated and/or verified before putting into service. The procedure starts with the definition of an instruments intended use.

Why is this being enforced?

Regulatory requirement GMP/GLP Quality organisations Audits and inspections

FDA WARNING LETTER

1. Written procedures had not been established for the calibration of analytical instruments and equipment in the Quality Control laboratories used for raw material, finished API and stability testing of *******. Furthermore, calibration data and results provided by an outside contractor were not checked, reviewed and approved by a responsible Q.C. or Q.A. official.

FDA WARNING LETTER

2. The **** systems calibrated by an outside contractor did not include verification of the precision (o/o RSD) of the autoinjector at more than one injection volume, the flow rate below 1 ml/min, or the wavelength accuracy for the wavelength regions used for testing of *****. In addition, the **** 3 software programs had not been verified or validated.

FDA WARNING LETTER

3. Records and documentation of instrumental equipment calibrations and laboratory testing are incomplete in that they lacked raw data spectra chromatograms, and calculations

WHERE IS IT DOCUMENTED?

CAPs
045 VALIDATION OF ANALYTICAL EQUIPMENT 015 SYSTEM SUITABILITY TESTING FOR INSTRUMENTAL TECHNIQUES

SOPs Validation Master Plan (used in Pharm Dev)

User Requirement Specification (URS)

The users definition of the performance requirements of the equipment. i.e. What do you want it to do?

Design Qualification (DQ)

Confirmation that the manufacturers specification is appropriate for the prospective purchasers use Justifies choice, i.e. results of evaluation

DQ

DQ CAN BE VERY SIMPLE FOR REPEAT EQUIPMENT e.g. JUST ANOTHER HPLC SYSTEM

Installation Qualification (IQ)

documents the installation in the selected user environment inventory check environmental location facility requirements assembly powers up? modules communicate?

Operational Qualification (OQ)

For testing the equipment in the selected user environment to ensure it meets our defined functional and performance specifications Pre-approved before use

Performance Qualification (PQ)

For testing that the system consistently performs as intended for the selected application Periodic calibration / maintenance Method specific system suitability checks

CHANGE CONTROL

A process to document changes made post qualification Need to make a judgement on what testing is required following significant change (e.g. repairs, moving) Like for like - no requalification necessary

Software Change Control

Firmware
Firmware is embedded software that controls an instrument. Occasionally it may be necessary to update firmware in order to fix known bugs or to allow compatibility with upgraded software. It will be necessary to have a change control form, but the tests carried out may be simple, for example a before & after chromatogram.

Software Change Control

Equipment Make & Type: Current Software Operating System Hewlett Packard G1314A BioMAX # 056432 Chemstation G2170A N/A Version VMP Reference A.06.04 PD/TM/99/041

Description of change (Attach extra pages if necessary) Update EPROM on HP UV detector to be compatible with Chemstation Version A.06.04 Tests to include internal checks plus Holmium Oxide calibration by Agilent technician System suitability run to be compared before and after upgrade

Software Change Control

Software
Software that runs on a PC and controls the instrument function and may carry out calculations. There may be several reasons to change software. In order to fix known bugs, to add functionality, or to work with a new computer operating system. It may also be necessary to re-load software in the case of a computer crash. It will be necessary to have a change control form, but the tests carried will be proportional to the changes made.

Software Change Control

Change Control Form for Computer Controlled Analytical Equipment
Equipment Make & Type: Current Software Operating System Hewlett Packard HPLC Systems BioMax 065003 Chemstation Windows NT Version VMP Reference A.06.04 & 8.0 PD/TM/99/041

Description of change (Attach extra pages if necessary) Upgrade operating system on PC to IDE 3.4 with associated Virus Check Software. Carry out Hewlett Packard Software Installation Qualification check. System suitability data from first HPLC run will be used for Equipment Qualification.

Testing will cover the following instruments, BioMax numbers 064998, 064970

RETROSPECTIVE VALIDATION

FOR EQUIPMENT IN EXISTENCE PRIOR TO A FORMAL QUALIFICATION PROCESS BEING ISSUED NEED TO CONSIDER WHAT TESTING IS REQUIRED TO BRING IT UP TO STANDARD SHOULD BE LITTLE NEED FOR RV NOW (as all current equipment should now be qualified)

Key Points

Proper planning Execution to the plan Documentation Define analytical technique, functional & operational specifications Document installation Test instrument for compliance to our specification

For several modules, use holistic approach Individual modules only as diagnostic Test key parameters before and during analysis SS, QC samples or defined critical parameters are acceptable

Summary of Procedure Create URS

Prepare VMP (or after DQ)

Purchaser to carry out DQ and suitably document

Agree written testing protocol(s) for IQ/OQ (with manufacturer if appropriate)

IQ and OQ protocols to be approved by purchaser (and PDQA for OQ)

IQ/OQ testing carried by manufacturer? YES Purchaser reviews the testing to ensure that the equipment meets agreed acceptance criteria and results satisfactorily documented NO Becomes the responsibility of the purchaser to carry out IQ and OQ testing

On satisfacory completion of IQ/OQ testing, obtain PDQA approval and store IQ and OQ protocols and VSR summary report in the equipment records

Periodically carry out PQ as defined in VMP and as appropriate, change control

CAP 045
Validation of Analytical Equipment

Drivers for a common Analytical Equipment Validation Standard

Avoid

re-inventing the wheel within GSK knowledge sharing reduced overall effort Meet compliance expectations common face to regulators Reduce variability (OE) approach - how we validate extent - how much we need to do terminology - use a single set for validation deliverables

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CAP documents are...

...formal company documents, and as such exist within the QMS framework ... the companys way of sharing analytical practice around the community of 3,500 analysts within both R+D and GMS ... not in themselves mandatory, but contain within them mandatory elements (often by cross-referral to policies, or pharmacopoeial monographs and chapters)

... written by, and for analytical practitioners

... source material for local procedures and guidelines

Document Hierarchy

Global Quality Policies 1204 1205 5103

Global Quality Guidelines

GQG GQG GQG GQG GQG 1204A 1204B 1204D 1205 1205A System-Specific Guidance IT iQMS Engineering Technical Processes
e.g. TP09

Analytical CAPs
e.g. CAP045

iQMS GSOPs

Local Procedures

Scope whats covered and what isnt

Key themes in CAP045 document set

Scalability doing enough according to level of risk and complexity

Classification an aid to applying the scalability based on complexity Consistent with other validation methodologies for example iQMS, TP09 Deliverables for the validation life cycle and how to document the validation effort

Scope of CAP45
All GMS Analytical Equipment
Laboratory-based equipment Computerised Analytical Equipment Analytical Equipment used for GxP-related activities B e s p o k e

Scope of Systems validated using CAP045

Non-computerised COTS equipment

Computerised COTS analytical equipment

Process Analytical Technology (PAT)

Client-Server Architecture-based systems

Bespoke hardware or software

Use CAP045.

Consider TP09

Use iQMS.

Consider GQG1205 or TP09

Scope - Validation Life Cycle

Requirements/Planning Specifications Design Qualification Testing Reporting

NOT...

Validation Maintenance activities Change Control, Periodic Review, Training, Calibration Decommissioning

Validation Effort

Simple COTS equipment used mostly in sample preparation or otherwise indirectly used in laboratory areas. Readings from these are not used to generate GxP data. Typically firmware-based no data storage, run-time parameters set when used. Not connected to another computerised system.

Equipment Classification
Non-electronic COTS devices and standards not depending on electronic logic, embedded logic or external computer systems to control instrument function. They do not store data on durable media or report information. All critical parameters are assured by a calibration program, maintenance program or similar. Simple, nonprogrammable firmware-based COTS equipment that provides a measurement reading via a digital display and/or to an attached printer. Will be calibrated periodically. Data storage will be limited to a few simple run-time parameter settings. Not connected to an external computer. Firmware based COTS systems but with additional features such as the ability to store run-time configurations as methods. Could be controlled from an external computer or system via an electronic interface. Usually will not store measurement data except where data logging is the main functionality. Calibrated periodically or at run-time. No direct programmable interface. Hardware firmwarebased or controlled by an external computer. Standard application software which will allow configuration of runtime parameters, instrument control, data acquisition and standard reporting functionality. Nonprogrammable data processing which may involve regulated records and signatures applicability. Usually stand-alone, not relying on separate controlling and postacquisition data processing systems. Typically utilises a local level of access control.

Direct impact: Rulers, non-digital thermometers Stirrers, hotplates, heating mantles, rotary evaporators, sonicators Indirect impact: check weights, mechanical friability testers, Utube viscometers

none

Digital thermometers, digital callipers, pH meter, balances, conductivity meters, digital viscometers

Autotitrators, HPLC or GC components e.g. pumps, column ovens, Chessel chart recorders

More complex systems mostly having PCbased application software. Usually programmable via standard method sequence lists. May utilise computer network functionality. Often these are hardware and software components used to control other standard lab equipment. Likely to involve regulated records/signatures. May acquire and utilise reference data as libraries, requiring advanced statistical or pattern recognition data processing. Typically uses operating system functionality for access control. Robotic workstation controllers e.g. Zymark, some NIR systems, NMRs, Mass Spectrometers

Stand-alone UV/Vis, FT-IR spectrometers, HPLC system software not connected via CDS.

C D Classification

What might the future look like?

Collaboration within the GSK analytical community reference document sets for preferred equipment (eg Agilent and Waters chromatography systems)
The means to locate existing validation for your equipment project for example a database of who has validated what analytical equipment NOT a database of all the validation documents themselves! gives a contact name at the site of interest use validation documentation as a template for your project may be able to reference some of it directly assumes a common documentation standard being used e.g. CAP templates

Validation Master Plan (VMP)

Validation Master Plan Prepared in advance

Approved by QA
Defines IQ, OQ, PQ, Change Control & Retrospective Validation Useful for frequently purchased equipment

References

CAP web site http://iwhc.gsk.com/cap Quality Management System web site http://quality.gsk.com/gms/qms/ Good Practice examples will appear here when available http://iwhc.gsk.com/gmsgcv/gcvdefault.htm?html/GoodPractice.htm