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

Sampling and testing for Quality Control Laboratories, Nairobi, September 20092 |

Overview of PresentationOverview of Presentation

The context – Procurement– Supply Chain

Testing requirements in procurement and supply

Risk mitigation

Sampling and testing for Quality Control Laboratories, Nairobi, September 20093 |

Key PlayersKey Players

• Raw materials suppliers

• Manufacturer

• National regulatory authority

• Procurement unit

• Logistics system

• End user

Qu

alit

y A

ssu

ran

ce

Sampling and testing for Quality Control Laboratories, Nairobi, September 20094 |

Do you sample and test your products ?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 ?

Sampling and testing for Quality Control Laboratories, Nairobi, September 20095 |

Procurement ContextProcurement 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

Sampling and testing for Quality Control Laboratories, Nairobi, September 20096 |

Sourcing / Prequalification of suppliersSourcing / 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

5

4

3

1

2

SatisfactoryType 2+

SatisfactoryType 2

TemporarlyAcceptable

UNSATISFACTORYSTABILITY

STUDIES

NO STABILITYSTUDIES

AVAILABLE

SatisfactoryType 4

PHARMACOPOEIABP/USP/Int.Ph.

IN HOUSEEQUIVALENT

METHODS

INHOUSE

IN HOUSE<

BP/USP/Int.Ph.

ANALYTICAL METHODS

NOT AVAILABLE

PHARMACOPOEIABP/USP/Int.Ph.

+Additional tests

DMF AVAILABLE

+ GMP

TF AVAILABLE

+ GMP

PRODUCERIDENTIFIED +

PRODUCERIDENTIFIED

PRODUCERNOT

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

specificationsTRILING. LABEL

SATISFACTORYGMP AUDIT

(product oriented)

SATISFACTORYGMP 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.STABILITYSTABILITY MFG SITE GMP

REG in an HighlyRegulated Country

MANUF: Non PIC/S or eq. country

Not REG in an Highly Regulated

CountryMANUF : 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

SATISFACTORYGMP AUDIT

(product oriented)Report received

Rating Table

THERAPEUTIC

EQUIVALENCE

5

4

3

1

2

SatisfactoryType 2+

SatisfactoryType 2

TemporarlyAcceptable

UNSATISFACTORYSTABILITY

STUDIES

NO STABILITYSTUDIES

AVAILABLE

SatisfactoryType 4

PHARMACOPOEIABP/USP/Int.Ph.

IN HOUSEEQUIVALENT

METHODS

INHOUSE

IN HOUSE<

BP/USP/Int.Ph.

ANALYTICAL METHODS

NOT AVAILABLE

PHARMACOPOEIABP/USP/Int.Ph.

+Additional tests

DMF AVAILABLE

+ GMP

TF AVAILABLE

+ GMP

PRODUCERIDENTIFIED +

PRODUCERIDENTIFIED

PRODUCERNOT

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

specificationsTRILING. LABEL

SATISFACTORYGMP AUDIT

(product oriented)

SATISFACTORYGMP 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.STABILITYSTABILITY MFG SITE GMP

REG in an HighlyRegulated Country

MANUF: Non PIC/S or eq. country

Not REG in an Highly Regulated

CountryMANUF : 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

SATISFACTORYGMP AUDIT

(product oriented)Report received

Rating Table

THERAPEUTIC

EQUIVALENCE

“Rating “3” is the minimum to allow a decision at the pharmacists level

Sampling and testing for Quality Control Laboratories, Nairobi, September 20099 |

Sampling and TestingReference samples, Batch testing

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

Risk

Pre

-qu

al

Sampling and testing for Quality Control Laboratories, Nairobi, September 200910 |

Sampling and TestingRoutine sampling and testing

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

Sampling and testing for Quality Control Laboratories, Nairobi, September 200911 |

Sampling and TestingOut of specification ?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

Sampling and testing for Quality Control Laboratories, Nairobi, September 200912 |

Sampling and TestingProduct complaints and Quality failure

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

Sampling and testing for Quality Control Laboratories, Nairobi, September 200913 |

Do you sample and test your products ?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 ?

Sampling and testing for Quality Control Laboratories, Nairobi, September 200914 |

Are all guidelines for inspections, sampling and testing relevant to pharmaceuticals ?

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

Sampling and TestingAQL Minor defects ( 21 allowed, 17 found )

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 Protruding growths

Black spots

Die included in laminate

Small chips with tablets Small growths on tablet

AQL Major defects A ( 7 allowed ) and B ( 10 allowed )

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

Sampling and TestingProduct complaints and Quality failure

Sampling and TestingProduct complaints and Quality failure

Sampling and testing for Quality Control Laboratories, Nairobi, September 200918 |

Any other questions ….. ?

Small group exercise …..