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

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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

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. 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