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Validation perceptions that may slow PAT development and implementation
Steve Hammond
Pfizer Global Manufacturing
Objective for this presentation
PAT will take significant resources to develop and implement
Stated intent of FDA “Enforcement policy does not impede innovation or
introduction of new manufacturing technologies” Process Analytical Technologies
Examples of the sort of things that might impede innovation and development of PAT
Avoid the “Cart before the horse paradigm”
Outline
Activities involved in developing and implementing PAT
Software Validation
Instrument PQ Tests during development
Concerns for the future - on-line analysers and performance compliance
Implementation activities Hardware development
Identify an instrument Have an instrument adapted to meet needs The easy bit, purely science based
Software specification Science based - but Validation is an issue - while developing the system Part 11 compliance a particular issue
System validation - during development Plan and documentation Perception is - FDA require full GMP protocol Variable - plant \ country dependant
Internal regulatory groups
Instrument qualification must be complete
Includes Performance Qualification
PQ is written before the application is fully developed
What should we test? How do you measure performance on the real system
Revised under change control and repeated when the instrument requirements are better understood
Software validation - Pt 11 Pfizer will only purchase software from audited and approved
suppliers. Includes Pt 11 compliance.
Vendors have been forced to put in large amounts of resources to provide “validateble software.” These efforts take time and money.
Part 11 compliance means at least a new version of software, sometimes a complete re-write.
New software is always a pain, if not a nightmare There will always be bugs Change control procedures then become a large burden while
testing the “fixed” versions
Over time compliance to Pt 11 will be the way of life
In the meantime it is slowing the development of PAT
Internal regulatory groups
Perception is that Pfizer can not use non compliant software in a GMP area
Must be pre-validated including Pt 11 compliance
IQ must be performed, signed off before data collection can begin. ~1 weeks work
Small bug fixes require change control report
Large bug fixes = new version = re-qualification
Internal regulatory groups
Data processing protocols
How will you get the result
Has to specified before and data is collected
“Mission impossible” “cart before the horse”
Implementation activities - time
Example - development of on-line blender system Cost in terms of man weeks
Hardware development 15
Software specification 1
System validation protocols 101
Total 117 weeks
117 weeks arises from constantly repeating change and review cycle, for documentation ,as development unfolds
Instrument performance tests
Science Vs tick the box
One “specification fits all” paradigm (USP) is documentation based, lacks scientific logic and represents a risk to the measurements
Vendor specifications based on science should be applied by users to ensure the base performance of the instrument.
Vary significantly with the type of instrument
Performance tests
. 010
. 015
. 020
. 025
Sin
gle
chan
nel s
pect
ra
7800 7600 7400 7200 7000 6800 6600
Wavenumber (cm-1)
Spectrometer calibration for H2O-bands
Resolution = 25 cm-1
Resolution = 2 cm-1
Target: 7,306.74 cm-1
. 010
. 015
. 020
. 025
Sin
gle
chan
nel s
pect
ra
7800 7600 7400 7200 7000 6800 6600
Wavenumber (cm-1)
Spectrometer calibration for H2O-bands
Resolution = 25 cm-1
Resolution = 2 cm-1
Target: 7,306.74 cm-1
What Pfizer uses
What USP says is OK
On-line instruments
Probes in a reactor cannot be removed to perform USP tests.
Alternative “performance” tests can be devised but they would be non-compliant with USP
Again the USP should not be looking for one specification fits all
Instrument performance testing is best prescribed by the vendor on a science base
Conclusions Proper validation of PAT systems must of
course be performed
However during development and information gathering stages, it can drastically slow progress
Lets have the horse before the cart, and be flexible in the approach to validation during development
Base performance qualification tests on science not lowest common denominator and ease of documentation