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. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 2 |2 | Overview of Presentation The context –Procurement –Supply Chain Testing requirements in procurement and supply Risk mitigation

3. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 3 |3 | Key Players Raw materials suppliers Manufacturer National regulatory authority Procurement unit Logistics system End user Quality Assurance

4. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 4 |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. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 5 |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. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 6 |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. 5 4 3 1 2 Satisfactory Type 2+ Satisfactory Type 2 Temporarly Acceptable UNSATISFACTORY STABILITY STUDIES NO STABILITY STUDIES AVAILABLE Satisfactory Type 4 PHARMACOPOEIA BP/USP/Int.Ph. IN HOUSE EQUIVALENT METHODS IN HOUSE IN HOUSE < BP/USP/Int.Ph. ANALYTICAL METHODS NOT AVAILABLE PHARMACOPOEIA BP/USP/Int.Ph. + Additional tests DMF AVAILABLE + GMP TF AVAILABLE + GMP PRODUCER IDENTIFIED + PRODUCER IDENTIFIED PRODUCER NOT IDENTIFIED CEP AVAILABLE Compliant With MSF specifications BILING. LABEL Compliant With MSF specifications ENGLISH ONLY MINOR DEVIATIONS MAJOR DEVIATIONS CRITICAL DEFICIENCIES Fully compliant With MSF specifications TRILING. LABEL SATISFACTORY GMP AUDIT (product oriented) SATISFACTORY GMP AUDIT (not product oriented) CORRECTIONS COMMITMENT RECEIVED CORRECTIONS + NEW AUDIT NEEDED DEFICIENCIES TOO NUMEROUS TO HOPE RAPID CORRECTIONS 6 REGISTRAT. / MANUFACT. F.P. ANAL. REFERENCE API QA SAMPLE / PACK. / LAB. STABILITY MFG SITE GMP REG in an Highly Regulated Country MANUF: Non PIC/S or eq. country Not REG in an Highly Regulated Country MANUF : PIC/S or eq. country REG: country of origin (non HRC) MANUF: Non PIC/s or eq. country REG : any other country MANUF: Non PIC/s or eq. country NOT REGISTERED. in any country MANUF: Non PIC/S or eq. country REG in an Highly Regulated Country MANUF: PIC/S or eq. country SATISFACTORY GMP AUDIT (product oriented) Report received Rating Table THERAPEUTICEQUIVALENCETHERAPEUTICEQUIVALENCE

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

9. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 9 |9 | Sampling and Testing Reference 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 Risk Pre-qual

10. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 10 | Sampling and Testing Routine 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 10 th, 25 th 100 th ( 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 testing for Quality Control Laboratories, Nairobi, September 2009 11 | Sampling and Testing Out 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 testing for Quality Control Laboratories, Nairobi, September 2009 12 | Sampling and Testing Product 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. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 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. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 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 Testing AQL Minor defects ( 21 allowed, 17 found ) Other Only 2 blister strips instead of 3 in box Missing package insert Poor die cut at blister Protruding growths Black spots Die included in laminate Small chips with tablets Small growths on tablet

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

17. Sampling and Testing Product complaints and Quality failure

18. Sampling and testing for Quality Control Laboratories, Nairobi, September 2009 18 | Any other questions ….. ? Small group exercise …..