Excipient Certification Scheme

Transcription

1 Excipient Certification Scheme CPhI Breakfast Briefings Feria de Madrid, 13 th October 2009 Dr Arnulf Heubner Member of the EFCG-Board and Chairman of the Pharmaceutical Business Committee (PBC)

2 Excipient Certification 1. Excipient Certification Why? 2. Supplier Qualification 3. Role of 3 rd Party Audits and Certification 4. New scheme principles and design 5. New scheme implementation benefits Certified

3 Excipient Certification Why? Excipients represent the major part of the final drug Excipients influence the efficiency of the API Certified Excipients Excipients Reasons enough for regulation!

4 Excipient Excipient β-mannitol δ-mannitol before after wet granulation The physico-chemical properties are influencing the galenics and in this way pharmacokinetic changes of the active ingredient can not be excluded

5 Excipient Certification 1. Excipient Certification Why? 2. Supplier Qualification 3. Role of 3 rd Party Audits and Certification 4. New scheme principles and design 5. New scheme implementation benefits Certified

6 Excipient Supplier Qualification Drug product manufacturers (users) have to qualify their suppliers A comprehensive assessment of Excipient quality The manufacturing process to make the excipient The distribution controls used to deliver the excipient to the drug product manufacturer The latter 2 aspects require a detailed assessment of the suppliers systems and capability A physical audit is the ideal way to achieve this

7 Excipient Supplier Qualification The purpose of this qualification is to ensure that the safety of the drug product is not compromised by the excipient Both manufacturing (GMP) and distribution (GDP) aspects need to be covered Failures at any point in manufacture or in the supply chain may put patients at risk The modern Pharmaceutical Paradigm requires a Quality by Design (Qbd ICH Q8) and a Risk management approach (ICH Q9) to determine the details of that qualification Those excipients posing the greatest risks require the most thorough controls

8 Excipient Certification 1. Excipient Certification Why? 2. Supplier Qualification 3. Role of 3 rd Party Audits and Certification 4. New scheme principles and design 5. New scheme implementation benefits Certified

9 Excipient Certification So we need a physical audit. 1000s of excipients 1000s of suppliers globally? Could the Inspectorates or Regulators perform the basic Audits of all these manufacturers AND distributors? Do users have the resources? Only a fraction of suppliers are audited Standards are inconsistent from one User to another Suppliers are at risk of death by audit Some sites could receive 100 or more per year Even today it is common to find suppliers with 1 person solely employed to deal with audits

10 WE SUGGEST: Excipient Certification an Internationally and regulatory acceptable Excipient certification system covering the Quality Management Systems in manufacture (GMP) and the supply chain (GDP) Users would then be able to focus qualification resources on the technical aspects and higher risk excipients Reducing the audit burden for for both parties

11 Excipient Certification Indeed, the FDA and EU have indicated very positively that: 3 rd Part Excipient Audits and Certification have a role to play The FDA has a system to approve 3 rd party auditing organizations For APIs, The December 2008 Pharmaceutical Package from the EU indicated that 3 rd party audits from accredited organisations would be acceptable The key components are in place then for the Excipient industry to implement a valuable Excipient Certification Programme

12 Who can Provide Auditors? With 1000s of excipient and 1000s of audits where do we find all the auditors? Could ISO auditors contribute? Pharmaceutical Packaging (ISO 15378)? Medical Device (ISO 13485)? ISO 9001 chemical / pharmaceutical sector? Existing 3 rd Party Audit BUT FDA and EU have indicated this is viable if and only if the auditors are competent So if auditors are deemed competent then we can use 3 rd parties with confidence

13 Excipient Certification 1. Excipient Certification Why? 2. Supplier Qualification 3. Role of 3 rd Party Audits and Certification 4. New scheme principles and design 5. New scheme implementation benefits Certified

14 Excipient Certification Project Principles Evolve existing best practices Base on the IPEC-PQG GMP Guide 2006 Base on IPEC GDP Guide 2006 & SQAS Distributor ESAD Scheme Align to ISO 9001 Many excipient suppliers are already ISO certified or familiar with this quality management system standard International in scope Excipients are a worldwide commodity Be valuable and acceptable to Suppliers, Users and regulators

15 Excipient Certification Project Principles Include as many Excipients as possible Classify excipients Set the standards in relation to the risk posed Set standards that are achievable Set standards that are auditable Address the definition of and policing of auditor competency Be accessible to existing 3 rd party audit organisations Consult with all Stakeholders throughout the project One session held in Europe in May 2009 One session held with FDA in July 2009

16 Excipient Classification Why classify Excipients? They have many diverse uses, functions, manufacturing processes and origins The risks posed to the patient are also very variable A one size fits all definition of GMP is not going to be appropriate 2 critical risk factors have been identified and verified as the most relevant in Classifying excipients 1. The route of Administration of the drug product (Dose) 2. The impact of the excipient manufacturing process variation on functionality (Function) These risk factors drive different GMP requirements

17 Excipient Classification It is critical that the Supplier and User of the excipient agree on the Classification in a 3 step process 1. Manufacturer classifies excipient, and assigns GMP Manufacturer to communicate result to Suppliers and Users (e.g. on CofA) 2. User to classifies excipient and requests GMP from supplier E.g. at contract review / Quality Agreement 3. User and Supplier to perform joint risk assessment Best option, but may not always be practical due to numbers of customers (1000s) and number of excipients (1000s) BUT an agreement at least on the GMP class must be part of contract review between the two parties as a minimum

18 Excipient GMP Certification will be against the core requirements in the IPEC-PQG GMP Guide 2006 as converted to ISO speak Suppliers with ISO 9001 will only require additional audit time to cover GMP Suppliers without ISO 9001 will require an audit covering GMP and the Quality Management System Two definitions of Excipient GMP containing the same requirements DOSE and FUNCTION additional requirements for GMP apply to both standards

19 Excipient GDP Certification will be against the core requirements in the IPEC GDP Guide 2006 as converted to ISO speak IPEC GDP Guide 2006 Provides additional explanation to the Good Trade And Distribution Practices For Pharmaceutical Starting Materials, World Health Organization, WHO Technical Report Series, No. 917, 2003

20 Excipient Certification 1. Excipient Certification Why? 2. Supplier Qualification 3. Role of 3 rd Party Audits and Certification 4. New scheme principles and design 5. New scheme implementation benefits Certified

21 Excipient GMP & GDP Certification Scheme How will 3 rd Party Certification Work? Once an agreement with 3rd Party Organisations to audit Organisations is in place, Auditor identification, training and assessment of competency can occur A list of 3 rd party audit organisations that have met the criteria and signed an agreement will be published Once auditors are assigned then audits can commence The 3 rd party certification body will indicate the audit outcome (pass/fail) which will be published (Pass / Suspended / Failed / Withdrawn etc.) to allow Users to validate the certificate presented by the supplier

22 Excipient GMP & GDP Certification Scheme Certification Plans Supplier or User commissions 3 rd Party Who is accredited by national competent authority Supplier passes evidence of GMP and GDP to User User passes details to regulators at inspection or in dossiers Virtuous circle CERTIFICATE OF GMP COMPLIANCE USERS SUPPLIERS & MANUFACTURERS CERTIFICATION ASSURED EXCIPIENT USE AUDIT REGULATORS 3rd PARTY ACCREDITATION

23 Excipient GMP & GDP Certification Scheme When will this be available? Classification Risk analysis and factors defined GMP Annex to ISO 9001 Drafted Enhancements for higher risks drafted NSF/ANSI standard sub team being assembled GDP Annex to ISO 9001 drafted Auditor Competency Structure outlined detailed work in progress Certification Scheme Work starting When? sometime in 2010 I hope! Certified

24 Excipient GMP GDP Certification This is a result of a cooperation of IPEC EU, IPEC US, PQG, FECC and EFCG. Thanks to all contributed. Special thanks to Iain Moore. Thank you for your attention