UNICEF s Quality Assurance System for Procurement of Finished Pharmaceutical Products

Transcription

1 UNICEF s Quality Assurance System for Procurement of Finished Pharmaceutical Products UNICEF Industry Consultation with Manufacturers and Suppliers of Finished Pharmaceutical Products 29 th 30 th September 2016, Supply Division, Copenhagen Dimitris Catsoulacos Quality Assurance Specialist

2 CONTENT UNICEF s Quality Assurance System Pre- Qualification Activities Good Manufacturing Practice Inspections & Findings International Collaboration on Good Manufacturing Practice UNICEF s Warehouse and Good Distribution Practice

3 UNICEF S QUALITY ASSURANCE SYSTEM WHO Model Quality Assurance System for Procurement Agencies MQAS - TRS 986 Annex 3 Pharmaceutical Inspection Cooperation Scheme (PIC/S) principles on Quality System Requirements for GMP Inspectorates Good Distribution Practice - WHO Good Distribution Practices for Pharmaceutical Products. TRS 957, Annex 5 - European Union Guidelines of 5 th November 2013 on Good Distribution Practice of medicinal products for human use Documentation system in place - Quality manual - Division procedures - Centre procedures * All procurement activities are centralized in UNICEF Supply Division (procurement by UNICEF country offices requires authorization)

4 PRE-QUALIFICATION ACTIVITIES Medicinal Products Product Questionnaire as in WHO Model Quality Assurance System for Procurement Agencies MQAS - TRS 986 Annex 3 Manufacturers/ Suppliers Review of Good Manufacturing Practice information: - Technical Questionnaire - Manufacturing license - GMP certificates - Site Master File - Recent Inspection Reports Contract Manufacture is accepted if both the manufacturer and the sub-contractor are approved by UNICEF

5 GMP INSPECTIONS Decision making process - Evaluation of GMP information - Regulatory framework in the country where the manufacturer is located - Prior UNICEF experience Plan Performance Report Agree on inspection date Request Site Master File Request Manufacturing License/ Authorization Provide inspection plan in advance Extend invitation to local authority On site inspection performed by UNICEF inspector or qualified UNICEF representative Verify compliance with WHO GMP Guidelines GMP inspection report within 3 weeks of inspection date Manufacturer s response/capa plan expected within 1 month of inspection report receipt. Official closing letter

6 INSPECTIONS KEY FACTS 133 GMP inspections carried out manufacturers found GMP non-compliant Re- inspection based on a risk based approach (frequency 2-5 years) Annual inspection plan established

7 MOST FREQUENTLY ENCOUNTERED DEFICIENCIES PER CATEGORY (1) QUALITY MANAGEMENT - Quality risk management principles not fully implemented - Poor handling of changes, deviations - Weak investigations poor CAPA implementation - Incomplete Product Quality Reviews ORGANIZATION AND PERSONNEL - Senior management responsibilities not well defined - Training in product release poorly documented - Training in aseptic procedures

8 MOST FREQUENTLY ENCOUNTERED DEFICIENCIES PER CATEGORY (2) FACILITIES - Poor separation between controlled and non-controlled areas - Inappropriate construction materials poor maintenance - Incorrect flow of personnel and materials - Risk of cross-contamination between penicillins and cephalosporins due to facility design - Double standard facilities - local vs export market EQUIPMENT - UTILITIES - Inappropriate design and qualification of HVAC system Unknown airflow patterns - Air re-circulation without HEPA filtration - Incomplete validation/ qualification/ calibration of production equipment

9 MOST FREQUENTLY ENCOUNTERED DEFICIENCIES PER CATEGORY (3) PRODUCTION - Manufacturing process not validated or not validated for all batch sizes - Incomplete maintenance and cleaning records line clearance - Media Fills QUALITY CONTROL - Incomplete analytical method validation - Poor qualification and control of API suppliers - On-going stability not always carried out - Establishment and handling of working standards

10 INTERNATIONAL COLLABORATION ON INSPECTIONS UNICEF relies on WHO PQ of vaccines, HIV, Malaria and TB products Joint inspections with WHO PQ, ICRC, MSF UNICEF is a Partner to the Pharmaceutical Inspection Cooperation Scheme (PIC/S) UNICEF shares inspection reports and information with international partners and vice versa GMP reports and information from partners is used to prioritize and in some cases to waive GMP inspections Good Manufacturing / Good Distribution Practice - Training It is expected that manufacturers that are found GMP non-compliant by UNICEF partners inform UNICEF immediately.

11 UNICEF SUPPLY DIVISION WAREHOUSE UNICEF SUPPLY DIVISION holds an Emergency Relief Authorization issued by the Danish Health and Medicines Agency is legally authorized to procure, hold, supply and export medicinal products including narcotics and psychotropics has to comply with Danish and EU Pharmaceutical Legislation Compliance with EU Good Distribution Practice Guidelines operations subject to repeated inspections by the Danish Health and Medicines Agency

12 UNICEF SUPPLY DIVISION WAREHOUSE GDP OPERATIONS (1) Personnel Training GDP training sessions Written evaluation Records Premises and Equipment Authorized access only Cleaning programmes Preventive pest control - Records Appropriate storage conditions Temperature and Humidity monitoring Qualification, calibration and maintenance of equipment Records

13 UNICEF SUPPLY DIVISION WAREHOUSE GDP OPERATIONS (2) Receipt Cleaning - Barcode verification Special Storage Conditions Visual inspection Product Dosage Form Strength Quantity Packing List Certificate of Analysis Manufacturer Expiry date Storage - Picking Electronic allocation of storage position Special Storage Conditions Cold Room First Expiry First Out principles Electronic system controls for product picking and expiry date

14 UNICEF SUPPLY DIVISION WAREHOUSE GDP OPERATIONS (3) Complaints - Recalls Complaints Database Investigations CAPA Recall procedure Instructions Records Self inspections Plan Records CAPA Annual Sampling and Testing Programme Selection of products based on risk factors - experience Quality Control performed by contract laboratories (WHO prequalified) * Pre-Delivery Inspections of Direct Shipments Third party/ Country Office Visual controls Random sampling

15 MOST FREEQUENTLY ENCOUNTERED DISCREPANCIES AT GOODS RECEIPT No packing list Missing certificate of analysis Loose labels on primary containers No package leaflet Certificate of analysis does not state the manufacturing site Very short remaining shelf life

16 STORAGE CONDITIONS DURING GDP Requirements TRANSPORT Storage conditions for medicinal products should be maintained during transportation within the defined limits as described by the manufacturers Risk assessment of delivery routes should be used to determine where temperature controls are required Equipment used for temperature monitoring during transport should be maintained and calibrated at regular intervals All manufacturers/suppliers will be requested to start documenting correct shipment conditions

17 Thank you for your attention Any Questions?