Quality Control Testing in Procurement

1. Quality Control Testing in Procurement Helene Möller, M.Pharm, PhD Interregional Seminar for Quality Control Laboratories involved in WHO Prequalification Programme and/or participating in respective sampling and testing projects, Nairobi, Kenya, 23-25 September 2009

2. Overview of Presentation • The context • Procurement • Supply Chain • Testing requirements in procurement and supply • Risk mitigation

3. Key Players Quality Assurance • Raw materials suppliers • Manufacturer • National regulatory authority • Procurement unit • Logistics system • End user

4. Do you sample and test your products ? • How many samples do I need to test ? • When to test ? • What to test for ? • How to interpret the results ?

5. Procurement Context National Procurement Body Procurement in National Market National Medicines Regulatory Authority ( NMRA ) National / International Procurement Body Procurement in Local / International Market Prequalification / qualification of suppliers

6. Sourcing / Prequalification of suppliers • Supplier evaluation, GMP compliance, • Dossier requirements and/or Contract clauses • Identifying the right to inspect and test goods • Appropriate product specifications • Validated test methods • Documentation of QA and certification requirements • Specifies product shelf-life requirements as appropriate • On-going supplier performance monitoring

7. RatingTable REGISTRAT. / MANUFACT. F.P. ANAL. REFERENCE SAMPLE / PACK. / LAB. MFG SITE GMP STABILITY API QA REG in an Highly Regulated Country MANUF: PIC/S or eq. country Satisfactory Type 4 PHARMACOPOEIA BP/USP/Int.Ph. + Additional tests CEP AVAILABLE Fully compliant With MSF specifications TRILING. LABEL SATISFACTORY GMP AUDIT (product oriented) Report received T H E R A P E U T I C E Q U I V A L E N C E 6 REG in an Highly Regulated Country MANUF: Non PIC/S or eq. country Satisfactory Type 2+ PHARMACOPOEIA BP/USP/Int.Ph. DMF AVAILABLE + GMP Compliant With MSF specifications BILING. LABEL SATISFACTORY GMP AUDIT (product oriented) 5 Not REG in an Highly Regulated Country MANUF : PIC/S or eq. country Satisfactory Type 2 IN HOUSE EQUIVALENT METHODS TF AVAILABLE + GMP Compliant With MSF specifications ENGLISH ONLY SATISFACTORY GMP AUDIT (not product oriented) 4 REG: country of origin (non HRC) MANUF: Non PIC/s or eq. country Temporarly Acceptable IN HOUSE PRODUCER IDENTIFIED + MINOR DEVIATIONS CORRECTIONS COMMITMENT RECEIVED 3 IN HOUSE < BP/USP/Int.Ph. 2 REG : any other country MANUF: Non PIC/s or eq. country UNSATISFACTORY STABILITY STUDIES PRODUCER IDENTIFIED MAJOR DEVIATIONS CORRECTIONS + NEW AUDIT NEEDED NOT REGISTERED. in any country MANUF: Non PIC/S or eq. country NO STABILITY STUDIES AVAILABLE ANALYTICAL METHODS NOT AVAILABLE PRODUCER NOT IDENTIFIED CRITICAL DEFICIENCIES DEFICIENCIES TOO NUMEROUS TO HOPE RAPID CORRECTIONS 1

8. RatingTable REGISTRAT. / MANUFACT. F.P. ANAL. REFERENCE SAMPLE / PACK. / LAB. MFG SITE GMP STABILITY API QA REG in an Highly Regulated Country MANUF: PIC/S or eq. country Satisfactory Type 4 PHARMACOPOEIA BP/USP/Int.Ph. + Additional tests CEP AVAILABLE Fully compliant With MSF specifications TRILING. LABEL SATISFACTORY GMP AUDIT (product oriented) Report received T H E R A P E U T I C E Q U I V A L E N C E 6 REG in an Highly Regulated Country MANUF: Non PIC/S or eq. country Satisfactory Type 2+ PHARMACOPOEIA BP/USP/Int.Ph. DMF AVAILABLE + GMP Compliant With MSF specifications BILING. LABEL SATISFACTORY GMP AUDIT (product oriented) 5 Not REG in an Highly Regulated Country MANUF : PIC/S or eq. country Satisfactory Type 2 IN HOUSE EQUIVALENT METHODS TF AVAILABLE + GMP Compliant With MSF specifications ENGLISH ONLY SATISFACTORY GMP AUDIT (not product oriented) 4 REG: country of origin (non HRC) MANUF: Non PIC/s or eq. country Temporarly Acceptable IN HOUSE PRODUCER IDENTIFIED + MINOR DEVIATIONS CORRECTIONS COMMITMENT RECEIVED 3 “Rating “3” is the minimum to allow a decision at the pharmacists level IN HOUSE < BP/USP/Int.Ph. 2 REG : any other country MANUF: Non PIC/s or eq. country UNSATISFACTORY STABILITY STUDIES PRODUCER IDENTIFIED MAJOR DEVIATIONS CORRECTIONS + NEW AUDIT NEEDED NOT REGISTERED. in any country MANUF: Non PIC/S or eq. country NO STABILITY STUDIES AVAILABLE ANALYTICAL METHODS NOT AVAILABLE PRODUCER NOT IDENTIFIED CRITICAL DEFICIENCIES DEFICIENCIES TOO NUMEROUS TO HOPE RAPID CORRECTIONS 1

9. Sampling and TestingReference samples, Batch testing Reference samples submitted in Expression of Interest for pre-qualification / bidding samples Batch testing Compliance to specifications documented, batch release and end of shelf life Packaging, inserts and labeling evaluated Standard procedure for routine sampling and testing Conformity to specifications tested Standard procedure for post distribution monitoring Pre-qual Risk

10. Sampling and TestingRoutine sampling and testing • Risk management approach considers known history of supplier • New suppliers, no / limited history , new products • Well known suppliers, reputable • Supplied in markets with stringent MRA control • Prepare a list of priority items for monitoring • Standard Procedure • Routine referral of every 10th, 25th 100th ( for example ) purchase order to QA regardless of order value • Referral of all purchase orders exceeding a certain order value • QA criteria for actions: • Pre shipment inspections • Arrival notification – received in good order ….. • Tracking device readings, sampling instruction

11. Sampling and TestingOut of specification ? • Prevention: Inspection/screening of certificates of analysis before shipment institutionalized in business processes • Standard operating procedure • Referral to QA team • Validation of process – confirm specifications, test methods • Assess seriousness of deviations • Consider testing by second independent laboratory • Notification of supplier, NMRA • Implement remedial action • Ensure that action was successfully executed

12. Sampling and TestingProduct complaints and Quality failure • Prevention: Standard procedure up to end-user level • Routine screening for quality defects, product failure • Reporting of complaints • Investigations and documentation needed • Immediate actions in case of concern • Decision making – to use or not, to quarantine, to return • Sampling and Testing • Referral to QA team • Follow standard procedure as for out-of specification • Refer to contracting team - Consider penalties against supplier

13. Do you sample and test your products ? • How many samples do I need to test ? • When to test ? • What to test for ? • How to interpret the results ?

14. Are all guidelines for inspections, sampling and testing relevant to pharmaceuticals ? For example:  ANSI/ASQC Z1.4, ISO 2859, BS6001 ? • AQL's: Acceptable Quality Levels – example of laboratory conclusion of conforming to visual inspection requirements of 3 batches sampled in one site • Critical Defects allowed: 0,1% 0 allowed, 0 found • Major defects A allowed: 0,25% 7 allowed, 4 found • Major defects B allowed: 0.40% 10 allowed, 8 found • Minor defects allowed: 2,5% 21 allowed, 17 found

15. Sampling and TestingAQL Minor defects ( 21 allowed, 17 found ) Other Only 2 blister strips instead of 3 in box Missing package insert Poor die cut at blister Die included in laminate Protruding growths Small growths on tablet Small chips with tablets Black spots

16. AQL Major defects A ( 7 allowed ) and B ( 10 allowed ) Other Two tablets included in one cavity Disintegrating tablets Poor die cut at blister Tablet partially formed Broken tablet < 25% Broken tablets > 25% Break in foil >25% Missing tablets

17. Sampling and TestingProduct complaints and Quality failure

18. Any other questions ….. ? Small group exercise …..