GxP Inspections within the Centralised Procedure

Transcription

1 GxP Inspections within the Centralised Procedure Brendan Cuddy Inspections Sector 2nd EMEA Workshop for Micro, Small and Medium- Sized Enterprises (SMEs) Focus on Quality

2 Agenda Introduction to work of the Inspections Sector GxP Inspections within the centralised procedure Regulatory framework for inspections Legal basis for inspections Timetable for inspections GMP Inspections information in the dossier & common dossier validation problems Post-authorisation Inspections GMP for IMP s

3 PROCEDURES Inspections Contribution to Centralised Procedure PRODUCT SPECIFIC Harmonisation and Provision of Guidance Scientific & Regulatory advice and guidance Submission & validation of applications Assessment reports, clock stop CHMP/CVMP Opinions and approvals Postauthorisation activities, incl. variations QWP GMP Inspectors Group GCP Inspectors Group (Liaison with other regulatory partners) MRA (Liaison with other regulatory partners) QWP GMP Inspectors Group GCP Inspectors Group GXP inspection coordination (pre-submission meetings) GXP inspection coordination (review of applications) GXP inspection coordination (inspection requests) GXP inspection coordination (inspection reports, manufacturing authorisations, compliance statements, contribution to EPARs) Certification of medicinal products Periodic GMP inspections GCP inspections of pharmacovigi lance systems Sampling and testing Rapid alerts (Product defects)

4 Inspections Sector Activities Majority of Inspections Sector operations are related to applications submitted to the EMEA (centralised procedures, pre&postauthorisation and referrals) iemea co-ordinates Inspection activities within the agreed timetable, ithere are no inspectors at the EMEA, we use the expertise of the EU Member States

5 Co-ordination of Pre-authorisation: GMP Inspections i in order to complete the assessment process. i Legal basis: Article 8.2 (or 30.2 for vet medicinal products) Council Regulation 726/2004. i Responsibility for carrying out inspections rests with the Supervisory Authority i Supervisory Authority, which is defined as the Competent Authority of the MS in which the product is either manufactured or imported within the EEA. 2/20/2008 5

6 COUNCIL REGULATION 726/2004 (CAP/EMEA) ART 57...THE AGENCY SHALL UNDERTAKE THE FOLLOWING TASKS WITHIN ITS COMMITTEES: i) co-ordinating the verification of compliance with the principles of good manufacturing practice, good laboratory practice and good clinical practice and the verification of compliance with pharmacovigilance obligations

7 Co-ordination of GMP Inspections i Type of inspections: - GMP: - For sites located in third countries, where EU-GMP is unconfirmed (no satisfactory EU inspection in the last 2 years on same building, similar type of product and equipment. - Product & Process: - To assess Quality issues raised by Rapp/CoRapp during assessment of Part II of the application. - Can apply to all sites wherever they are located (EEA/Third countries)

8 Timetable for Inspections Pre-Authorisation Pre-submission Primary Evaluation Stop Clock Secondary Evaluation Opinion Decision Post Authorisation Phv INS. VALIDATION OF THE MAA DOSSIER D. 80 ASSESSMENT REPORT FINAL IR SUBMITTED TO EMEA/CXMP BY DAY 180 D.0 D.120 D.121 D.210 D.277 -Cause - Surveillance -System focused GCP: specific obligation, new extensions, new clinical data ADOPTION OF THE INSPECTION REQUEST ANNOUNCEMENT TO THE APPLICANT (WITHIN 10 DAYS SINCE THE ADOPTION) - CONDUCT OF THE INSPECTION - IR SENT TO INSPECTEE - INSPECTEE 15 D. TO RESPOND GMP: Cause Surveillance

9 Shorter timetables Some procedures have shorter timetables; Generic Applications Applications granted accelerated assessment If inspection requested during the assessment then there will be a clock stop and secondary evaluation phase

10 Composition of Inspection Teams iinspection team: Leading inspector(s) Scientific experts appointed on the advice of the Rapporteur and / or Co-Rapporteur. inumber of inspectors: Normally two inspectors Higher numbers may be justified.

11 Fees Council Regulation 297/95 specifies fees payable for inspections Implementing rules for Council Regulation adopted by EMEA management Board set the level of the fees. Inspection fee per site inspected, and sub-divided between EMEA and inspectorates; For 3 rd country inspections, travel expenses etc. are payable separately. DON T FORGET TO APPLY FOR YOUR FEE REDUCTION

12 GMP Inspections Information in the Dossier Part 1A Application Form Annexes manufacturing licences, GMP Certificates, QP Declaration. Module 3.

13 Common Dossier Validation Problems Manufacturing Authorisations Site not licensed Site has IMP Licence Licence does not include activities to be performed. Inconsistent manufacturing/testing site information throughout dossier QP Declarations QP cannot provide declaration. Declaration does not cover all drug substance manufacturing sites Declaration not signed by QP or by all QP s Testing upon importation

14 Post-Authorisation GMP Inspections Co-ordination of GMP inspections during post authorisation procedures Variations, Line extension Co-ordination of for cause inspections GMP Problems Quality Defects

15 Post-Authorisation GMP Inspections Co-ordination of routine GMP inspections The EMEA prepares a program of re-inspections in Third Countries (TC) for centralised products. Re-inspections are also adopted by the CxMP. MSs may provide feedback on the program (e.g. delegation, assistance from another MS, combination with national products). Inspections are carried out at least every 2-3 years, unless a more frequent basis is recommended by the inspectors.

16 GMP Inspections: IMPs Responsibility rests with Supervisory Authority Routine inspections of sites of manufacturing authorisation holders (IMPs) In response to CT Application (if needed) In response to MA Application (if needed) In 3 rd countries (risk-based approach) Import to a single point within the Community could simplify clinical trial authorisations as there would be only one Supervisory Authority Other triggers e.g.: Follow up of other GMP or GCP inspections Complaints/quality defects/rapid alerts

17 Contacting Inspections Sector For general questions concerning GMP: For questions concerning GMP inspections: For general questions concerning GCP: For general questions concerning GLP: To report a suspected product defect or recall: QDEFECT@emea.europa.eu Web :

18 SME Workshop THANK YOU FOR YOUR ATTENTTION