FOOD AND DRUG ADMINISTRATION

CENTER FOR DRUG EVALUATION AND RESEARCH

OFFICE OF PHARMACEUTICAL SCIENCE, HFD-003

PRODUCT AND PROCESS DEVELOPMENT WORKING GROUP MEETING OF

THE PROCESS ANALYTICAL TECHNOLOGIES (PAT) SUBCOMMITTEE

Meetings held in Gaithersburg, Maryland

June 12, 2002, 3:00 pm to 5:00 pm

June 13, 2002, 8:30 am to 12:00 noon

Working Group Discussants

Judy P. Boehlert, Ph.D., Chair, and Member, Advisory Committee for Pharmaceutical Science

Ronald Miller, Ph.D., Bristol-Myers, Squibb

David R. Rudd, Ph.D., GlaxoSmithKline

John G. Shabushnig, Ph.D., Pharmacia Corporation

Gopi Vudathala, Ph.D., Sanofi-Synthelabo

Walter Dziki, Ph.D., Abbott Laboratories

R. Thomas Cambron, Ph.D., P&G Pharmaceuticals

Brian Curtiss, Analytical Spectral Devices

Anserd Fraser, AAI International

Colin Walters, Schering-Plough

Efraim Shek, Ph.D., Abbott Laboratories

Yuan-yuan Chiu, Ph.D., CDER, FDA

Frank Holcombe, Jr., Ph.D., CDER, FDA

Thomas Layloff, Ph.D., Center for Pharmaceutical Management

Notes were recorded by: Rajendra Uppoor, Ph.D., CDER, FDA.

Limited ad-hoc participation by members of the public who were in attendance at the meeting was also permitted intermittently by Dr. Judy P. Boehlert, on both days, June 12 and 13, 2002.

NOTES OF PUBLIC MEETING "AS-IT-WAS-RECORDED" DURING THE MEETING

Note: These notes constitute written "transcript" of recordings, which was displayed in public to all attendees who were present as the meetings.

Spectroscopic and acoustic methods for granulation.

Equivalence to a standard method for replacement.

Suitability of method for all.

Replacement test correlated with something else.

New specification based on a new method?

NIST workshop September/October 2002.

Process Control End-points. Signal to a threshold.

End point models are easy to implement?

Physical domain, chemical domain: Univariate correlation?

Scale up differences have to be determined.

Demonstrate basic scientific principles

Guidance in writing, with specifics, "What to do when there is a sensor failure".

PATs more sensitive to mishaps. Hence guidance in case of sensor failures.

Process to a desired signal, than to a fixed time, through a signal route, time.

Remain sensitive to manufacturer (component) change?

483: "Mix until dissolved".

Raw material differences; "signature" for defining end point.

Q # 3: Built-in redundancy

List in-process measurements predictive/replacement/reflective/correlative of product

characteristics.

"Decision is equivalent" - measurement/test may not be. Batch quality decision has to be

established.

Technique-End points" have to be validated.

Parking lot items: Key glossary items, signature, fingerprint, in-line, on-line, at-line, off-line.

Multiple tests to measure same attributes.

Refinement of definition (PAT)

End point is harmonized - How to get there is not.

Concept of selective rejection. Broken tablets in blisters removed.

 

Identify critical parameters: Addition rate, mixing rate.

Process deviation "catching" ability.

Guarantee "performance" in drug products.

"OOS" issue using PATs.

Reject bad tablets on-line? Cost?

Can not correlate current method to PAT data?

"Trend analysis" and new requirements using PATs.

Test and limits should be linked. Different test, then different limits.

Goal is probably not to "improve" quality - current quality is good.

Shift population model, then shift acceptance criteria.

PAT applications with well behaved products - should not become "gold standard".

Slide # 11 (of Ajaz's presentation on June 12, 2002)

No "sample" with PATs. Use PATs for different reasons, and in different ways. Not direct

interpretability on end product quality.

Identify critical variables. Develop robust product, based on data captured. PATs provide

more information than "now".

Appropriate PAT to measure or control desired variable.

methods.

Make a change and see the effect in instrument/equipment, that may/will affect quality. Now

it is not visible until end product testing.

Incentive? For R&D?

R&D should become comfortable in using PATs.

R&D, regulatory, quality to be trained by industry also.

 

 

 

 

Process signature

PAT Measurement

End product attribute

Dissolution

Hardness

Content Uniformity

Perform multivariate analysis.

May get signal, but not understand its implication such as stability.

Signature

Signature utility

What data to keep?

Issue guidance, Workshop, Training, Communication back and forth with Industry;

Case studies from Industry.

Team review-inspection will help.

Note: Portions of the above notes were used in preparing the "Summary of Discussions" of Product and Process Development Working Group deliberations. Dr. Judy P. Boehlert presented the "Summary of Discussions" to the PAT Subcommittee, in the afternoon session of the meeting, on June 13, 2002. That document can be found on FDA's website, http://www.fda.gov/ohrms/dockets/ac/acmenu.htm.