WHO-PQP GMP Inspections: Updates

Transcription

1 JOINT UNICEF, UNFPA & WHO MEETING WITH MANUFACTURERS AND SUPPLIERS OF DIAGNOSTIC PRODUCTS, FINISHED PHARMACEUTICAL PRODUCTS AND ACTIVE PHARMACEUTICAL INGREDIENTS September 2013, Copenhagen, Denmark WHO Prequalification of Medicines Programme WHO-PQP GMP Inspections: Updates Deusdedit K. Mubangizi Technical Officer Acting Head of Inspections World Health Organisation EMP/QSM/PQM

2 WHO-PQP GMP Inspections: Updates In this presentation: Introduce the team Enhanced focus on international collaboration Use of SRA-PIC/S inspection reports New guidelines: QRM, validation, hold time Inspection timelines and statistics Current trends and press headlines: worrying Towards harmonization and consistency among inspectors and TA experts How to contact WHO-PQP inspection team 2

3 The inspection Team Deus Mubangizi Ag. Head of Inspections Ian Thrussell Expert Inspector Stephanie Croft Vimal Sachdeva Xingyu Chen Iveta Streipa-Naumane CROs/CRM Training/FPP/RH APIs QMS/Complaints/QCLs 3

4 4 Prequalification: Inspection Processes By a team of qualified and experienced inspectors WHO representative (qualified inspector) Inspector from well-established inspectorate (Pharmaceutical Inspection Cooperation Scheme countries PIC/S) National inspector/s invited to be part and observe the inspection Observer from recipient/developing countries (nominated by DRA of the country) Scope: Compliance with guidelines: GMP for API and FPP sites, GCP for CROs, GLP for FPP/API factory QCL, CRO-BAL, NQCL, IQCL Compliance with the dossier and commitments: Data verification data manipulation, falsification, (validation, stability, clinical, bioanalytical)

5 International Collaboration has been enhanced Joint Inspections Coinspectors Observers International API inspection Collaboration Collaboration in handling GMP related crises Mainly EU Inspectorates EAC NMRAs PICS Inspectorates Independent Experts Host country inspectorates Recipient country NMRAs USFDA, EMA, TGA, WHO EU NCAs (UK, FR, IT, GER, IR) EDQM Teleconferences Joint investigations Coordinated actions, press releases Share the workload and promote avoiding duplicative inspections. Facilitation of harmonization through joint inspections and sharing of outcomes. Capacity building of NMRAs inspectors. Facilitating use of WHO-PQ inspection results in national regulatory environment for information and decision making. 5

6 Prequalification Programme: Use of Inspection reports from other NMRAs Inspectorates whose reports are used: PICS member inspectorates EU (EDQM + EMA) USFDA new member of PICS What GMP evidence to submit: SMF Up-to-date Inspection report - conducted NMT 2 years + CAPAs to deficiencies + final conclusion Product Quality Review not more than 1 year old Review of the report: scope covered the specific API, FPP or BE study Is comprehensive and supports the final outcome. PQP reserves the right to inspect the manufacturer as long as product is active in WHO-PQP. on-going GMP compliance will be confirmed by WHO-PQ 6

7 New Guidelines: approved or under discussion More focus on Pharmaceutical industry than HACCP Quality Risk Management WHO-TRS981-Annex2 Draft Guidance on hold-time studies Draft on Non-Sterile Process Validation Applies to MRA and Industry Facilitates science-based decision-making Resources can be focused on risks to patients Restrictive and unnecessary practices can be avoided The level of effort, formality and documentation of the QRM process should be commensurate with the level of risk For materials for further processing (dispensed materials, intermediate materials and bulk materials) Guidance on: max storage periods with no hold time data design & number of batches for hold time studies stages & tests for hold time studies Apply quality risk management and quality by design principles Requires thorough knowledge of product and process development studies; previous manufacturing experience; and quality risk management (QRM) principles. Life-cycle approach links product and process development, validation of the commercial manufacturing process and maintenance of the process during routine commercial production 7

8 Risk-based approach in: definition and classification of deficiencies Deficiencies are descriptions of non-compliance with GMP requirements. A distinction is made between deficiencies as a result of: - a defective system or, failure to comply with the system. Deficiencies may be classified as: Critical Observation potential risk harm to the user Major Observation major deviation from GMP/GCP Minor or Other Observation departure from good practice 8

9 Risk-based approach in: Conclusion following an inspection When there are "other" observations only: considered to be operating at an acceptable level of compliance with WHO GMP. The manufacturer is expected to provide CAPAs. CAPAs are evaluation and followed up during the next routine inspection. When the are "other" and a few "major" observations: compliance with WHO GMP is made after the CAPAs have been assessed. CAPAs for majors to include documented evidence of completion. CAPAs paper evaluated ± an on-site follow up inspection. When there are "critical" or several "major" observations: considered to be operating at an unacceptable level of compliance with WHO GMP guidelines. Another inspection will most likely be required 9

10 Information put in public domain - for use by NMRAs and Procurers: WHOPIRs and NOCs These are published in response to the WHA Resolution WHA57.14 of 22 May 2004, which requested WHO, among other actions: "3. (4) to ensure that the prequalification review process and the results of inspection and assessment reports of the listed products, aside from proprietary and confidential information, are made publicly available;" A WHO Public Inspection Report (WHOPIR) reflects a positive outcome after an inspection A Notice of Concern (NOC) is a letter reflecting areas of concern where the non-compliances require urgent attention and corrective action by the manufacturer or research organization. 10

11 Update on timelines and statistics First inspection: 6 months from dossier acceptance for assessment or from site confirms it is ready. Routine inspection: ± 3 months from due date. Notification: 1 2 months before inspection. Onsite days: 3 5 days. Report: 30 days from last date of inspection. CAPAs: 30 days from receipt of report (max 2 rounds, comprehensive, on CDs and not hard copies) Closing of inspection: 6 months from inspection. Follow-up inspection: 6 months from inspection 11

12 Inspections performed (N=185) FPP API CRO QCL 65 12

13 Analysis of inspection of observations Total number of Observations Average number of observations All FPP API CRO QCL Total Observations Critical Observations Major Observations Average all observations All FPP API CRO QCL Average critical Average Major

14 Worrying Trends Press is awash with NOCs, warning letters, import alerts, statements of non-compliance, complaints, recalls, etc. Data integrity and falsification. «Show-case» and «shadow» industries. «Knee-jerk» responses to inspection observations. Many «Awaits CAPAs» on routine inspection: poor maintenance of quality systems work hard to pass first inspection and then go on holiday 14

15 Meeting to harmonise interpretation of GMP requirements: May 2013 Attended by: Inspectors and co-inspectors Experts for Technical assistance Topics Discussed: Product quality review (PQR) Deviations, out of specifications and investigation practices Risk management and Root cause analysis Heating, ventilation and air conditioning (HVAC) system and GMP for hazardous substances Outcome: Questions and Answers still under finalisation. 15

16 16 Selected GMP topics for manufacturers and GMP inspectors Nairobi, May 9-12, 2011

17 HOW TO CONTACT US ధనయ ల 谢谢! 17