WHO Prequalification of Team Introduction to medicines inspections technical updates

Transcription

1 WHO Prequalification of Team Introduction to medicines inspections technical updates Deusdedit K. Mubangizi Group Leader, Inspections WHO Prequalification Team 1

2 In this presentation: > Role of WHO-PQT towards MDGs. > Inspectorate within new WHO-PQT within EMP/RHT > How to get inspection Information on the website > Risk-based inspections > Use of inspection reports by other authorities. > Triggers for the inspection. > Statistics > Worrying trends > Best approaches to responding to inspection observations. > Upcoming guidelines > How to contact the inspection team. 2

3 WHO-PQ contributes to the Millennium Development Goals (MDGs): Eight international development goals that 192 United Nations member states and at least 23 international organizations have agreed to achieve by the year Reduce child mortality 5. Improve maternal Health 6. Combat HIV/AIDs, Malaria and other diseases 3

4 Structure of Department of Essential Medicines & Health Products Essential Medicines and Health Product [EMP] Policy, Access and Use [PAU] Regulation of Medicines and other Health Technologies [RHT] Public Health, Innovation and Intellectual Property [PHI] Technologies Standards and Norms [TSN] Regulatory Systems Strengthening [RSS] Prequalification Team [PQT] Safety and Vigilance [SAV] 4

5 Structure of the Prequalification Team Prequalification Team Coordinator s office Vaccines Assessment Medicines Assessment Diagnostics Assessment Inspections Technical Assistance/Labs Administrative team 5

6 The inspection Team Deus Mubangizi Group Leader, PQT Inspections Ian Thrussell Senior Inspector Being processed OHSE, Sabine Diagnostics Stephanie Croft CROs/CRM Vimal Sachdeva Training/FPP/RH Xingyu Chen Iveta Streipa-Naumane APIs/Complaints QMS/Statistics/QCLs Vacant Vaccines Sun Jinglin, China (has left) Rotational Fellow, China/India Kate Kikule, EAC/NDA-UG Rotational Fellow, AFRICA Ana Garcia Miguel Secretary 6

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

8 1.2 Risk based approach to inspections Ref: SOP 401.1: Inspection Frequency and Scheduling > Inspections are scheduled on a risk basis, taking into account all known factors that could affect quality, safety and efficacy, including the following: results of previous WHO inspections results of inspections by other National Regulators type of APIs, products and dosage form manufactured or -activities performed recalls or complaints since last inspection results of product testing significant changes within the manufacturer, e.g. changes to key personnel, buildings, equipment, products etc. any other relevant information (e.g. variations)

9 WHO-PQT-Rx: Use of Inspection reports from other NMRAs - SOP Desk Review Inspectorates whose reports are recognized: PICS member inspectorates EU (EDQM + EMA) USFDA new member of PICS What GMP evidenceto 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 FPP or API Is comprehensive and supports the final outcome. PQP reserves the right to inspect the FPP/API manufacturer as long as product is active in WHO-PQP. on-going GMP compliance will be confirmed by WHO 9

10 22/09/2014 WHO-PQ Inspections > Eligibility for WHO-PQ inspections: companies that are producing or intend to produce products invited under EOIs and have either submitted dossiersto WHO-PQfor assessment. or that demonstrate a serious intention to submit dossiersto WHO-PQ for assessment within an acceptable period. > Trigger for inspection: Only following submission of the product dossier. > Target: within 6 months of dossier acceptance for assessment and preferably after 1 st round of assessment. 10

11 22/09/2014 Exceptions to the general rule > Companies producing certain high priority products: pre-inspection PRIOR to PQ submission to expedite access and assessment of products by early identification of GMP gaps and implementation of improvements in GMP. Currently only DMPA Injection in the RH EOI eligible on acceptance for rolling submission. > Under WHO-PQ/ Nigeria-NADFC joint special project: declared intention/commitment to build a regional capacity in certain essential medicines. Compliance with GMP declared via pre-inspection WHOPIR on WHO-PQ website. > Certain manufacturers of certain priority medicines of critical interest outside the EOI: at the request of the relevant Disease Programmes of WHO, e.g. NTDs. > Delayed at the request of the manufacturer: persistent requests for a delay or a refusal of an inspection may be considered grounds to stop assessment, and ultimately to reject the application. 11

12 22/09/2014 Clearing misconceptions > Pre-visits by personnel working with WHO providing technical advice are not inspections. > Demonstration visits performed by WHO PQT Inspectors as part of training organised by or supported by WHO PQT cannot be used to declare GMP compliance. These are usually targeted on very specific training needs and rarely cover all aspects of GMP guidance. Although feedback will be provided to companies who volunteer to host these visits, they should not be considered or represented as WHO inspections 12

13 WHO-PQT-Rx: Target Inspection Timelines > 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 13

14 22/09/2014 STATISTICS: INSPECTIONS 2013 FPP SITES 34 API SITES 22 CRO SITES 11 QCL SITES 16 TOTAL 83 NEW 32 REINSPECTION 51 COMPLIANT 49 AWAITS CAPAs 12 NOT COMPLIANT 16 PRE-AUDITS 6 TOAL 83 14

15 22/09/2014 DATE REPORT SENT Total 2883 Number 81 Average 36 Minimum 0 Range: days Maximum 148 First Quartile, Q1 15 Median, Q2 28 Median: 28 days Target: 30 days Third Quartile, Q : New Sites COMPLIANT AWAITS CAPAs NOT COMPLIANT TOTAL FPP SITES API SITES TOTAL : Re-inspections COMPLIANT AWAITS CAPAs NOT COMPLIANT TOTAL FPP SITES API SITES TOTAL

16 22/09/2014 NEW SITES: Days from acceptance to first date of inspection FPP+API Total 2284 Number 23 Average 99 Minimum 13 Rage: days Maximum 263 First Quartile, Q1 33 Median, Q2 87 Median: 87 days Target: 180 days (6 months) Third Quartile, Q3 145 FPP Total 1387 Number 16 Average 87 Minimum 27 Range: days Maximum 261 First Quartile, Q Median, Q2 70 Median: 70 days Target: 180 days (6 months) Third Quartile, Q API Total 897 Number 7 Average 128 Minimum 13 Range: days Maximum 263 First Quartile, Q1 69 Median, Q2 130 Median: 130 days Target: 180 days (6 months) Third Quartile, Q

17 22/09/2014 RE-INSPECTIONS: Days from acceptance to first date of inspection FPP+API Total 92 Number 33 Average 3 Minimum -136 Rage: days Maximum 175 First Quartile, Q1-23 Median, Q2 1 Median: 1 day Target: 180 days (6 months) Third Quartile, Q3 27 FPP Total -208 Number 18 Average -12 Minimum -136 Range: days Maximum 103 First Quartile, Q1-53 Median, Q2-4 Median: -4 days Target: 180 days (6 months) Third Quartile, Q3 26 API Total 300 Number 15 Average 20 Minimum -48 Range: days Maximum 175 First Quartile, Q1-6 Median, Q2 3 Median: 3 days Target: 180 days (6 months) Third Quartile, Q

18 Worrying Trends Media is awash with NOCs, warning letters, import alerts, statements of non-compliance, complaints, recalls, etc. > Data integrity and falsification unbalanced focus on QC (quality built in not tested in). > «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 18

19 RESPONSES TO INSPECTION OBEERVATIONS (1) > An inspection is a sampling exercise and by consequence not all aspects of the manufacturing process may be inspected. The manufacturer is encouraged to take the information provided in the inspection report as examples and to consider vertical and horizontal analysis of the issues. nonconformities described in the report that are designated to be of lesser degree of severity, may increase in severity if not satisfactorily addressed in a timely manner.

20 RESPONSES TO INSPECTION OBSERVATIONS (2) > The manufacturer is required to submit an action plan in response to the observations and all nonconformities noted in the final inspection report within 30 days after receipt of the report. > It is suggested that the action plan incorporates: root cause analysis (how/why did this happen), analysis regarding related areas (is this same issue impacting/occurring elsewhere), correction (fix now) with completion dates, corrective action (to prevent recurrence) with completion dates and, The plan for demonstration of effectiveness of the actions taken.

21 22/09/2014 New Format for Submission of CAPAs Name of Manufacturer Unit number Production Block Physical address Contact person(s) and address Date of inspection Inspector(s) Observations Root cause analysis (Additional information may be attached as annexes) Critical 1. a) a) 2. a) a) Major 3. a) a) 4. a) a) Other 5. a) a) 6. a) a) Correction and proposed corrective action (Additional information may be attached as annexes) The steps that have or will be taken for the demonstration of effectiveness of the actions taken Timeline Assessment by inspector 21

22 22/09/2014 Upcoming New and Revised Guidelines > Good data management new guidance > Good Manufacturing Process for hazardous substances update > Good Manufacturing Practice for APIs (Q&As) collaboration with ICH IWG update > Supplementary guidance on GMP: validation for non-sterile process validation and other areas Proposal for revision > Guidance for Inspectors on hold-time studies general guidance > Quality risk management Q&As > Guidance for organizations performing in vivo bioequivalence studies revision > Classifications for inspection deficiencies new guidance for inspectors > Model inspection report update 22

23 HOW TO CONTACT US 谢谢! 23