EDQM Certificates of Suitability: Cooperation Among Inspectorates in Europe And Beyond

EDQM Certificates of Suitability: Cooperation Among Inspectorates in Europe And Beyond 14 th International Conference of Drug Regulatory Authorities Pre-ICDRA Meeting Dr Susanne Keitel European Directorate for the Quality of Medicines & HealthCare Council of Europe

Content The Council of Europe and EDQM The Certification Procedure The EDQM Inspection Program International Collaboration Inspection Statistics Outlook 2010 EDQM, Council of Europe, All rights reserved 2

The Council of Europe Founded on 5 May 1949 by 10 countries An international organisation in Strasbourg which comprises 47 countries of Europe. The primary aim of the Council of Europe is to create a common democratic and legal area throughout the whole of the continent, ensuring respect for its fundamental values: human rights, democracy and the rule of law. 2010 EDQM, Council of Europe, All rights reserved 3

The EDQM The European Directorate for the Quality of Medicines & HealthCare (EDQM), a Directorate of the Council of Europe Our vision is to be a leader in protecting public health by establishing high quality standards for: medicines for human and veterinary use, blood transfusion and organ transplantation; the safe and appropriate medication; participating in programmes targeted towards the protection of consumer health. 2010 EDQM, Council of Europe, All rights reserved 5

The Certification Procedure One out of three options to submit the quality documentation for an API in EU licensing procedures Referred to in the EU pharmaceutical legislation Open for substances covered by a Ph.Eur. Monograph Certifies that impurities can be adequately controlled by the monograph(s) Includes inspections 2010 EDQM, Council of Europe, All rights reserved 6

The Certification Procedure (cont.) Additional benefits: Centralised assessment of APIs: attractive to applicants and National Competent Authorities Identification of potential divergent practices by national assessors may contribute to more consistent assessment approaches across Europe 2010 EDQM, Council of Europe, All rights reserved 7

The Certificate of Suitability (CEP) Certifies that the quality of a given substance can be suitably controlled by the Ph.Eur. monograph - with additional tests, if necessary (stated on the CEP). It DOES NOT certify that a batch or batches of the substance complies with the Pharmacopoeia monograph. It IS NOT a GMP certificate 2010 EDQM, Council of Europe, All rights reserved 8

GMP Requirements for API Active substance must be produced according to EU GMP (Directives 2001/83/EC and 2001/82/EC) It is the responsibility of the MAH to ensure EU GMP compliance of the active substance manufacturer Declaration from the MAH Qualified Person(s) (QPs) in the MA (and any subsequent variation(s))

Challenges in A Globalised World Complex and fragmented supply chain with a growth in adulteration/counterfeiting activities Shift of API manufacture away from Europe Large number of API manufacturers involved, including increasing trade with intermediates, API starting materials and presence of alternative sources Increasing need for on-site verification of GMP compliance? 2010 EDQM, Council of Europe, All rights reserved 10

EDQM Inspection Program Part of the Certification Procedure, based on a mandate given by the European Commission Maybe performed before or after a CEP is granted Aim: to verify compliance with submitted dossier EU GMP Part II EU GMP Annexes (e.g. Annex 1 / sterile manufacture)

Selection of Sites Done in accordance with EU Commission guidance (EMEA/INSP/GMP/313538/ 2006) request from the assessors sterile substances may be several triggers involved re-inspection regulatory environment of the manufacturing site inspection by equivalent authority Based on a risk-based approach => NO routine inspections! 2010 EDQM, Council of Europe, All rights reserved 12

Legal Framework The Competent Authority may inspect an API manufacturer in order to ensure that the manufacturing authorisation holder of a medicinal product has fulfilled its obligations under Article 46 (f) and/or Article 50 (f) of the below mentioned Directives (Article 111 of Directive 2001/83/EC and Article 80 of Directive 2001/82/EC) 2010 EDQM, Council of Europe, All rights reserved 13

EDQM Inspection Program Draft annual program circulated to Member States for comments and presented to GMP/GDP Inspectors Working Group at EMA for discussion. Program adopted by Certification Steering Commitee. Final program circulated to all EEA Member States Competent Authorities 2010 EDQM, Council of Europe, All rights reserved 14

How The System Works Inspection performed by team, usually composed of EDQM inspector and inspector coming from EU/EEA or MRA National Competent Authority Compliance with submitted dossier and EU GMP verified EDQM informs local inspectorate about date and scope of inspection and welcomes participation of local inspectors as observers 2010 EDQM, Council of Europe, All rights reserved 15

EDQM and the EMA GMP/GDP Inspectors Working Group Discussion of EU Regulations, GMPs, GDPs Management of MRAs in the field of GMP Management of the Community Procedures EudraGMP database access International API Inspection Pilot Program (2007) Gathers authorities performing significant number of API inspections outside their territories: FR, DE, IE, IT, UK, EDQM, AU, US Aim: to make best use of inspectorates resources Based on sharing inspection reports or/and performing joint inspections 2010 EDQM, Council of Europe, All rights reserved 16

EDQM and GMP Inspectorates Inspections performed by team composed of EDQM inspector and inspector from EU/EEA or *MRA National Competent Authority Austria Czech Republic Denmark Finland France Germany Greece Hungary Ireland Italy Latvia Netherland Romania UK Sweden Spain *Switzerland *Australia + WHO 2010 EDQM, Council of Europe, All rights reserved 17

API Pilot Project Overall objective is to see whether greater international collaboration and information sharing can help: to better distribute inspection capacity, allowing more sites to be monitored and reducing unnecessary duplication. 2010 EDQM, Council of Europe, All rights reserved 18

API Pilot Project Principles: Sharing of inspection reports of conducted inspections Sharing information on inspection planning Joint inspection with or without scope extension. 2010 EDQM, Council of Europe, All rights reserved 19

API Pilot Project Involved Authorities: EU: France, Germany, Ireland, Italy, United Kingdom Council of Europe: EDQM MRA: Australia (TGA) US: FDA Current Status: Interim Report available (http://www.ema.europa.eu/docs/en_gb/document_library/report/2010/10/wc500097431.pdf) Collaboration to continue 2010 EDQM, Council of Europe, All rights reserved 20

API Pilot Project Benefits for EDQM: - Broader coverage of manufacturing sites by using external inspection reports - suspension/restoration of CEPs (sterile) based on inspection/re-inspection performed by Germany - Joint inspections with TGA - Extension of the inspection s scope (i.e. covering an API subject to the CEP procedure) saved resources - International networking / confidence building 2010 EDQM, Council of Europe, All rights reserved 21

EDQM Inspection Statistics 2004-2009 100% 90% 80% 70% 60% 50% 40% 30% Elsewhere EEA Asia other China India 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 EDQM, Council of Europe, All rights reserved 22

Statistics 1999-2010 (Exp) Number of EDQM inspections per year Outside EU/EEA EU/EEA 35 30 25 20 15 10 5 0 2010 EDQM, Council of Europe, All rights reserved 23

Statistics 2004-2010 (Exp) EDQM Inspections 2010 - Repartition of the number of inspector-days Sweden 3% Denmark 4% Spain 4% Norway 3% UK 3% Greece 3% Romania 9% EDQM 40% Italy 3% Switzerland 5% Finland 3% Germany 11% France 9% 2010 EDQM, Council of Europe, All rights reserved 24

2009 Review 29 sites inspected by EDQM 32 sites covered by exchange of information with other inspectorates 10 found non-compliant with EU GMP 3 sites borderline (follow-up on going) CEPs suspended: 11 Dossiers closed: 2 CEPs withdrawn after suspension due to negative re-inspection: 3 3 CEPs suspended for two manufacturing sites due to refusal to be inspected 2010 EDQM, Council of Europe, All rights reserved 25

Outlook Further develop risk-based approach when elaborating programme Reinforce collaboration and sharing of information with EEA and international inspectorates in order to optimise inspection ressources through: (Pilot) program for exchange of information on API (EMA) GMDP Inspectors Working Group: EEA members Committee of officials of PIC Scheme (PIC/S) Confidentiality agreement with PIC/S, TGA Australia, USFDA Confidentiality agreement with WHO being finalised EUDRA GMP database 2010 EDQM, Council of Europe, All rights reserved 26

Thank you for your attention! 2010 EDQM, Council of Europe, All rights reserved 27