1. EXCiPACT TM Certification 3rd Party Certification for Pharmaceutical Excipient Suppliers EFCG Update at CPhI, 9 th October 2012 Frithjof Holtz, Merck KGaA

2. EXCiPACT TM Certification  EXCiPACT TM  Voluntary international Good Manufacturing and Good Distribution Practice (GMP/GDP) certification scheme for pharmaceutical excipients  Ensures current GMP and GDP requirements applied to pharmaceutical excipients through a recognized auditing and certification process  Motivation for the voluntary 3rd party certification scheme:  Regulators expect Market Authorization Holders to comply with GMP regulation and to secure their supply chain  One way to achieve this is by an increase of periodical, physical audits  The economical burden associated with these requirements impacts both suppliers and users but benefits outweigh costs  EXCiPACT approach  international in scope  makes use of the existing best practice, standards and guides  the industry response to help mitigate the risks and address the auditing challenge  Contributors : 2

3. EXCiPACT TM Certification Principle ISO 9001 certification EXCiPACT TM certification successful EXCiPACT TM 3PAO audit GMP / GDP (IPEC Guides) 3

4.  Products  Approval/Qualification of 3rd party audit companies issuing the EXCiPACTTM certificate  Excipient GMP Annex to ISO 9001 and/or ANSI standard  Excipient GDP Annex to ISO 9001 and/ or ANSI standard  Requirements for auditor competency and 3rd party audit organizations providing certification  Services  Oversight of pharmaceutical excipient manufacturer and distributor - Certification  Auditor competency; development and qualification  Website with certification status, including data on compliance, list of registered auditors EXCiPACT TM Certification Products and Services Managed by EXCiPACT Association, a not-for-profit organisation www.excipact.org 4

5.  Supplier passes audit report to excipient user  User verifies audit report and certificate with EXCiPACT  Agreement with supplier  Provides audit report and certificate to supplier  Legal Agreement with 3 rd Party  Audit Organisations (3PAO)  Publish on website  Certificates  Certified bodies  Certified Auditors meeting competency criteria EXCiPACT TM Certification The process and relationship EXCiPACT Association 3rd Party Audit Organisation Excipient user Excipient Supplier Excipient user 5

6. Cost for EXCiPACT TM Audit Excipient Supplier Pharmaceutical Company Audit fee 15,000 € Certificate fee 5,000 € Internal cost 5 – 10,000 € TOTAL 25 – 30,000 € TOTAL COST in 3 years 30,000€ Audit reduction of 25-50% at 12 audits per year assumed 20,000 – 50,000 € per year Audit reduction of 25-50% 50,000 – 100,000 € per year TOTAL SAVINGS in 3 years 60’000 – 150,000 € TOTAL SAVINGS in 3 years 150,000 – 300,000 € BENEFIT 30,000 – 120,000 € 150,000 – 300,000 € EXCiPACT TM Certification Cost savings for stakeholders 6

7. EXCiPACT TM Progress since CPhI 2011 (1 of 2)  Launched publically in January 2012: 150+ delegates plus support from FDA and MHRA  Legal basis for EXCiPACT Association established, base funding completed, and operational processes/staff in place  4 x 2 day auditor training courses completed  Legal Agreements close to signature with 3rd Party Audit Organizations 7

8. EXCiPACT TM Progress since CPhI 2011 (2 of 2)  Pilot audits planned to check the performance of GMP and GDP standards  Equivalent NSF-ANSI standard close to agreement  Public webinar well received  Many presentations and articles written to raise industry awareness 8

9. “… the holder of the manufacturing authorisation shall ensure that the excipients are suitable for use in medicinal products by verifying the appropriate good manufacturing practice on the basis of a formalised risk assessment …”  If the Commission would propose an excipient risk assessment similar to the previous concept of “certain excipients”, viz., classifying excipients as of low, medium or high risk. then …  EXCiPACT TM may replace the auditing of low and medium risk excipients by pharmaceutical companies and …  could permit pharmaceutical companies to perform audits on high risk excipients or specific needs *Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the prevention of the entry into the legal supply chain of falsified medicinal products EXCiPACT TM and the EU Falsified Medicines Directive (FMD)* 9

10. Thank you EXCiPACT TM Certification 10