EXCIPACT Pharmaceutical Excipient Certification

1. EXCIPACTPharmaceutical Excipient Certification Milan September 8th 2010 Iain Moore, Project Coordinator

2. Excipients are components of medicines Excipeints have no therapeutic activity Excipients formulate active pharmaceutical ingredients into finished drug dosage forms Value of the global excipients market: €3 bn Thousands of different excipients used all dosage forms Excipients can influence the potency and bioavailability of the active ingredient Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

3. Motivation Safety of medicines for patients – recent tragedies Drug producers have to qualify their suppliers Traditionally by a mixture of paper and physical audits Now a regulatory expectation of physical audits on ALL suppliers – no current alternative to physical audits = Armies of auditors and auditees A familiar story? Transparent certification schemes for all components of a drug benefit the entire industry Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

4. Why Certification? Absence of regulations for excipients Certification Scheme for self regulation Ability for supplier to initiate process Applicability to manufacturers and distributors of excipients Well developed and accepted assessment model Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

5. Excipient Certification Project commenced in May 2008 with EFCG and IPEC Europe, now comprises 5 trade associations • FECC – European Association of Chemical Distributors • IPEC-Americas • IPEC Europe • PQG - Pharmaceutical Quality Group (UK) Excipact - Minimise the Risks, Maximise the Benefits

6. Excipient Certification Challenges to a user global audit program • User Issues • Suppliers will not agree to an audit • Not enough days in the year for an audit to every supplier • Travel costs continue to rise • Language barriers • Employees don’t want to travel • In house auditors are not familiar with chemical processing resulting in less effective audits • Supplier Issues • Not enough days in the year for an audit from every customer • Language barriers • Value of business with user does not justify audit time Excipact - Minimise the Risks, Maximise the Benefits

7. Excipient Certification Certification & 3rd Party Audits • Provides information on Supplier’s GMP practices from experienced auditors with knowledge of excipient manufacturing & GMPs • Allow companies to focus resources on excipients with highest risk • Reduces audit load for suppliers and users • Can allow a level playing field for all • Help small companies (both users and suppliers) and those with limited budgets • Makes 100% audit verification of suppliers practical Excipact - Minimise the Risks, Maximise the Benefits

8. Excipient Certification Nothing in FDA regulations prevents using 3rd party auditors to evaluate suppliers • Sec. 211.34 Consultants. • Consultants advising on the manufacture, processing, packing, or holding of drug products shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained. Records shall be maintained stating the name, address, and qualifications of any consultants and the type of service they provide • FDA have publicly stated 3rd party audits are acceptable Excipact - Minimise the Risks, Maximise the Benefits

9. Excipact Goals Acceptance by all stakeholders International: certificates accepted globally Inclusive: applicable to as many excipients as possible Certification assessable for as manyaccredited 3rd party organizations as possible Evolutionary: builds on existing guides and standards Simple: easy to understand and apply for all stakeholders Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

10. Excipient Certification GMP Annex to ISO 9001 containing specific requirements for GMP – Certificate as Annex to ISO 9001 – same model as EFfCI Suitable for excipient manufacturers Harmonised requirements with IPEC GMP Guide for Pharmaceutical Excipients

11. Excipient Certification GDP Annex to ISO 9001 containing specific requirements for GDP – Certificate as Annex to ISO 9001 – same model as EFfCI Suitable for excipient suppliers (e.g. distributors) Allowance for different distributor/trader operations (trading, warehousing, re-packaging, bulk transport etc.) Harmonised requirements with IPEC GDP Guide for Pharmaceutical Excipients In-line with SQAS ESAD Section F&G (www.sqas.org) Where there is overlap, GMP- and GDP-Annexes contain same requirements

12. Quality of auditors is critical Competency framework defined using ISO 19011 Alternative starting routes to qualification possible i.e. experienced in ISO 9001, GMP or GDP Considered best practices e.g. SQA and Qualified Person assessment processes Training Guide included Training programme for auditors to be developed Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

13. Auditor competency & qualification Assessment of knowledge & audit skills will be Tertiary scientific education Work and Audit experience ISO 9001 knowledge GMP/GDP knowledge Excipient Knowledge Knowledge assessed orally or by exam Supervised first audit Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

14. Certification Scheme Program elements Excipact to be a Legal Entity representing partner organizations Certification Body: Accredited to ISO 9001, ISO/IEC Guide 65, ISO 17021 or equivalent and verified by Excipact Excipient suppliers to be Certified on a 3 year cycle Annual site surveillance audit Triennial recertification audit Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

15. Certification Scheme Audit Documentation Audit Report lists observations and rates findings as critical, major or minor Technical Experts review audit report and findings, recommend certification if No critical, no major without CAPA, no minors that indicate failure of quality system element Audit Report available to pharmaceutical customer with excipient supplier approval Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

16. Certification Scheme Website List of Third Party Certification Providers Directory of certified excipients suppliers List of certifications suspended and withdrawn Program Procedures Appeals Complaints Requirements of Third Party Certification Provides Study Guide for Excipient GMP Certification Auditors Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

17. Certification Scheme Participation Legal Agreement between Excipact and 3rd Party Assessment Body Confirmation of certification held by 3rd party assessment body Confirmation of auditor competency and qualifications to the requirements of the scheme Excipient Certification Excipact - Minimise the Risks, Maximise the Benefits

18. EXCIPACT Minimize Risks – Maximize Benefits None of this would be possible without the commitment and contribution from the volunteers working in the task forces and the on the steering committee. Many thanks to them. iain.moore@croda.com Dr. Iain Moore Product and Quality Assurance Manager Croda Europe Ltd Cowick Hall, Snaith East Yorkshire, DN14 9AA Phone +44 (0) 1405 863282 Thank you for your attention Excipact - Minimise the Risks, Maximise the Benefits