Dr Patricia Rafidison IPEC Federation Dow Corning Corporation ExcipientFest Asia November 28th Beijing

The journey update Promoting the quality, safety and functionality of pharmaceutical and related healthcare products worldwide *IPEC: International Pharmaceutical Excipient Council

The journey update  Recognises that the drug market is global, including excipient sourcing  Monitors regulatory developments from multiple perspectives and geographies  Represents an industry speaking as ‘one voice’ for common global issues  Builds on IPEC « unique » set up: users, producers and distributors of excipients sharing the same « quality and safety » vision to benefit patients

The journey update IPEC Federation creation – Cannes France

The journey update Concept was born in 2009 – Evolved from TriPEC Meetings with Pharmacopoeial Discussion Group IPEC foundation: IPEC Americas, IPEC Europe, JPEC The need – Formalize interactions between PECs – Provide a mechanism for developing consensus- based positions across geographies – Set priorities for issues that interest/affect members globally

The journey update  Federation statutes ◦ ‘Not for Profit’ association based in Belgium (ASBL)  Membership: ◦ Full members: IPEC Americas, IPEC Europe, IPEC Japan and IPEC China ◦ Associate partners (Argentina, Brazil)  Operations ◦ One « assemblée générale » per year ◦ Governance principles detailed in the IPEC Federation Policy Manual  IPEC interactions ◦ Each PEC is independent and responsible to monitor and comment on regulations within its geography ◦ Input from other PECs may be provided either individually, or via the Federation

The journey update  Efforts are currently underway to form IPEC India as an Associate member of the Federation  Formal association registration is in process and is expected completed in December 2012

The journey update  The IPEC Federation has formed formal partnerships with other trade associations in Brazil and Argentina  These partners are translating IPEC Guidelines into their local languages  The IPEC Federation works with each organization to hold periodic excipient conferences in its country

The journey update

 Managing global regulatory expectation ◦ Identify emerging regulations impacting excipients ◦ Establish position papers on any relevant advocacy activity  Harmonisation of standards ◦ Work with PDG to continue the harmonisation process of pharmacopoeial monographs ◦ Develop harmonised voluntary industry guidance for global use  Promoting supply chain security ◦ Excipient risk management ◦ Third party certification

The journey update Urgency Impact on Members QbD /PAT / FRC Managing Global Reg Expectations Paediatrics GTIs DS Recomb. Excip Harmonisation PZ Safety Resid. Solv Supply Chain (incl. Counterfeiting) Risk Mgmt / contingency DC Innovation / New Excipients 3 rd Party Certification DC New Analytical Techniques Allergens Nanotech Excip. Comp Co- proce ssed Atypical Actives JSW Visible Particules DS E DMF DL Elemental impurities JSW

The journey update  Harmonisation of excipients monograph globally  Excipients certification program  Risk management /assessment of excipients  ICH Q3D Elemental analysis  Excipient Master files  Apply appropriate GMPs to atypical actives

IPEC and stakeholders Drivers  Lack of consistency for the same excipient in monographs  Tests to be repeated or different in most regions  Increased costs for non- value added activities  Impact on registration submissions  Pharmacopoeia : establish PDG (Pharmacopoeial Discussion Group)  IPEC Federation: Voice of the excipient industry users, prodcuers and distruibutors providing expertise and data collection  Participate in the design of the future for harmonisation

The journey update  Further the work of excipient harmonisation ◦ Continued partnership with PDG (Pharmacopoeial Discussion group)* via a Biannual meeting with the IPEC Federation  Contribute to the future vision of pharmacopoeia, ◦ Considering new pathways forward to speed up process ◦ Prospective harmonization of new excipient monographs * PDG is made of EP (European Pharmacopoeia), JP (Japanese Pharmacopoeia), USP (United States pharmacopoeia)

Drivers  Risks in the pharmaceutical supply chain are not just API related, excipients may be impacted  Regulators expect “Market Authorization Holders” to secure their supply chain  The appropriate way to achieve this is by means of periodical, physical audits  The economical burden associated to these requirements are impacting both manufacturers and users  Excipact TM developed by industry consortium (IPEC Europe, IPEC Americas, EFCG,FECC, PQG)  Third party auditing scheme developed using GMP and GDP auditable standards  Excipact Standards are now published; ANSI standard are currently developed, and are aligned  Share audits programme provided by IPEA, accredited by ANSI  Both programmes use IPEC-PQG GMP or/and IPEC-PQG GDP guidelines  Third party certification bodies have signed up for EXCIPACT TM IPEC and stakeholders

The journey update  A voluntary self regulated initiative of the global pharmaceutical excipient manufacturing, distributing and processing industry supported by excipient users  EXCiPACT TM ensures contemporary GMP and GDP requirements are applied to pharmaceutical excipients through a recognized auditing and certification process thereby increasing safety and reliability as well as transparency, of the pharmaceutical supply chain  EXCiPACT TM is accepted by all major stakeholders including relevant authorities globally  As an independent organization EXCiPACT TM will be able to objectively set GMP and GDP standards today and in the future  EXCiPACT TM certification provides a cost-efficient method of ensuring GMP and GDP are applied throughout the pharmaceutical supply chain by reducing the audit burden

The journey update 1. Supplier selects approved 3 rd party audit company 2. EXCiPACT TM issues registration no to 3 rd party audit company 3. Audit will be performed and certificate issued 4. Supplier pays audit fee (including certification fee) to 3 rd party certification body 5. 3 rd party audit company pays certification fee to EXCiPACT TM and informs about audit result 6. Supplier provides audit results to excipient user and upon request audit documentation 7. Excipient user can verify the audit with EXCiPACT TM 8. EXCiPACT TM reserves rights to attend audit or to analyse audit report in order to warrant standards 18 EXCiPACT TM 3rd Party Audit Organisation Excipient user Excipient Supplier Excipient user

Drivers  Regulators require a risk based approach when implementing regulations  Increased enforcement of regulation impacting excipients, and expectation to comply with GMP and/or GDP using risk assessment  Risk management tools exist ( ICH Q 9), the specificity of excipients is not addressed  Excipient Risk Analysis and Evaluation to be developed by IPEC ◦ Considerations for and perspective of the Excipient Maker ◦ Considerations for and perspective of Excipient User  Excipient Risk management guideline currently being developed IPEC and stakeholders

Drivers  Elemental impurities is addressed in USP Chapters and is close to implementation (2013) and will impact excipients  ICH Q3D working group on elemental impurities has recently been set up to address this subject  Suppliers of excipients are looking to assess their products so that they are using the appropriate test methods and detection limits, which will be necessary once the limits are established  IPEC Federation observer at ICH Q3D (2010)  Input from most impacted suppliers gathered via workshop in 2012  Coalition from industry provides feedback to stakeholders with data and request to allow reasonable timeline for compliance IPEC and stakeholders

Drivers  Excipient-sensitive information needs to be protected, whilst facilitating users’ registrations  Systems exist in some geographies (USA, Japan); new systems are being developed (China)  No process in Europe  Share information about developing regulation, and highlight excipients specificity  Advocate the creation of DMF system in most geographies  Share DMF template, and suggest process to manage confidentiality  Reinforce the need for harmonisation and mutual acceptance of excipient global regulatory status IPEC and stakeholders

Drivers  Some excipients are used as active ingredients in pharmaceutical applications  Regulations are evolving, and require GMP for API to be applied to these ingredients  Organise conferences and workshop to clarify the status of these ingredients  To prevent a shortage of these ingredients, industry proposes adopting IPEC- PDG GMP guidelines as an appropriate reference IPEC and stakeholders

The journey update  Enforcement of regulations for excipients becomes a reality ◦ In China, new regulations for excipients prepared by SFDA ◦ In the USA, FDA reinforces the need for increased controls of excipients ◦ In Europe, the Falsified Medicines Directive makes GMP applicable to excipients, using a risk-based approach ◦ Excipients GMP are expected to apply in Brazil

The journey update  IPEC Federation is the unique association that regroups excipient experts from the user, producer and distributor community  IPEC Federation is developing via its members a strong foundation to support industry and authorities to provide safe and quality excipients for the benefit of patients  The world has no boundaries anymore, harmonisation and collaboration between all stakeholders is essential to continue to protect public health

Questions?