1. Pharmaceutical Quality by Design: A PAT Equipment Vendor Certification Proposal Charles P. Hoiberg, Ph.D. Regulatory CMC and QA Pfizer Pharmaceutical Sciences and Neil Lewis, Ph.D. Analytical Imaging Systems Malvern Instruments Advisory Committee for the Pharmaceutical Sciences October 5-6, 2006

2. Certification RationaleCertification Rationale Benefits of the Certification ProcessBenefits of the Certification Process Expectations from the stakeholdersExpectations from the stakeholders –for the Vendor –for the Pharma firms –from Regulators Proposed Certification ProcessProposed Certification Process Use of Vendor CertificationUse of Vendor Certification Support in placeSupport in place Next Steps and TimelineNext Steps and Timeline QuestionsQuestions Agenda : Overview - IFPAT MA

3. IFPATma is an organisation consisting of Pharma companies and instrument vendors. The management committee of IFPATma have taken on the task of developing a system of audits to bring the instrument audit process in to the GMP’s for 21 st Century philosophy, and to avoid the expensive replication of audits. What is IFPATma?

4. 1)Reduce the burden of audits to both the purchaser, & the vendor. This will be achieved through the development of an independent, certified audit programme, that requires an instrument manufacturer to undergo a single audit, that establishes whether or not they can be generally recognised as Pharma Industry Compliant and which can be quoted by any purchaser of equipment as showing due diligence in their compliance records for the instrument they have installed. IFPATma Objectives

5. 2) Change the focus of audits from “tick the box compliance” to risk based, science driven audits. The new focus will be on proving an instrument is “fit for purpose”. That it can truly function in a robust way, as a PAT instrument, installed in a plant environment. IFPATma Objectives

6. Certification RationaleCertification Rationale Benefits of the Certification ProcessBenefits of the Certification Process Expectations from the stakeholdersExpectations from the stakeholders –for the Vendor –for the Pharma firms –from Regulators Proposed Certification ProcessProposed Certification Process Use of Vendor CertificationUse of Vendor Certification Support in placeSupport in place Next Steps and TimelineNext Steps and Timeline QuestionsQuestions Agenda: Overview - IFPATMA

7. The rationale for putting in place this vendor certification process is to produce significant technical and business benefits for:The rationale for putting in place this vendor certification process is to produce significant technical and business benefits for: –Users –Vendors –Regulators Certification will enable PAT system users, and regulatory bodies to be sure that:Certification will enable PAT system users, and regulatory bodies to be sure that: –Vendors comply with a minimum set of agreed criteria during the development, manufacture and test of PAT systems prior to shipment to a customer. –The certification will cover the instrumentation, associated software and sample interface. Certification Rationale

8. Benefits of the Certification Process Pharma firms will then not have to carry out their own quality audit of the vendor.Pharma firms will then not have to carry out their own quality audit of the vendor. Vendors will be assured that customers of PAT systems will not expect or carry out their own quality audit of their systems or products.Vendors will be assured that customers of PAT systems will not expect or carry out their own quality audit of their systems or products. All parties will reap benefits in:All parties will reap benefits in: –Rapid and efficient qualification process prior to sale and delivery/acceptance of a system. –Reduced cost of quality – no vendor quality audit necessary. –Implementation of a high-quality, systematic, uniform and traceable certification process for PAT hardware and software throughout the pharmaceutical industry.

9. Expectations for the Vendor To support the certification process the vendor is expected to have in place the following:To support the certification process the vendor is expected to have in place the following: –Product Development Process –Preferably a certified Quality Management System –Quality Improvement Process –Product Specification –Robustness Design Criteria To be derived from a consensus such as ASTM, ANSI, ASQ, ASME, ISO, etc.To be derived from a consensus such as ASTM, ANSI, ASQ, ASME, ISO, etc. –Final Test process and procedures –Internal audit processes to test compliance with internal processes

10. Expectations for the Pharma Firm To support the certification process the Pharma Company is expected to have in place the following:To support the certification process the Pharma Company is expected to have in place the following: –An internal consensus that this certification process satisfies the appropriate part of their quality management system for vendor assessment of PAT equipment and systems. –No further technical or quality audit of the vendor is required.

11. Expectations from the Regulators To accelerate the uptake of the certification process by both Users and Vendors it is expected that the regulators support this certification initiative.To accelerate the uptake of the certification process by both Users and Vendors it is expected that the regulators support this certification initiative. –The regulators would expect to see a PAT system certificate during an inspection. –Regulators would know the certification process and know that the PAT product or system under inspection had been certified by an expert in that technology. –Regulators could then focus on how the PAT product or system had been implemented by the user.

12. Proposed Certification Process Vendor Pre-CertificationVendor Pre-Certification –PAT Vendor Certification Guidelines use to carry out internal vendor audit –Vendor carries our remediation if necessary Vendor Certification AuditVendor Certification Audit –Vendor audited by approved auditors –Audit report issued –Remediation plan put in place and executed if necessary –Vendor Certified Vendor Certificate created for systemVendor Certificate created for system

13. Use of Vendor Certification A Pharma firm wanting to use a vendor’s system as part of a PAT implementation would request a copy of the Vendor PAT System certificate from the vendor or the certifying body.A Pharma firm wanting to use a vendor’s system as part of a PAT implementation would request a copy of the Vendor PAT System certificate from the vendor or the certifying body. Review of the certificate will reveal that the system of interest has been created in a quality environment and has a specification suitable for use.Review of the certificate will reveal that the system of interest has been created in a quality environment and has a specification suitable for use. No further inquiry of the vendor should be necessary.No further inquiry of the vendor should be necessary.

14. Support in place Pharma Firms Vendors include: BRIMROSE

15. Next Steps and Timeline Next Steps:Next Steps: –Increase the consensus across the Pharma firms and Vendors –Identify the certification body –Create the Vendor Certification guidelines Develop a timeline to deliver the certificate scheme in the next two to three yearsDevelop a timeline to deliver the certificate scheme in the next two to three years Secure Concurrence from the Agency on our Proposed Vendor Program - “PAT Equipment Certification”Secure Concurrence from the Agency on our Proposed Vendor Program - “PAT Equipment Certification”

16. Questions and Comments