WHO - PSM

MaterialsPharmaceutical Quality,

Good manufacturing Practice & Bioequivalence

Kiev, Ukraine3 - 7 October 2005

Maija Hietava M.Sci.Pharm

Quality Assurance and Safety: Medicines, Medicines Policy and Standards, Health Technology and Pharmaceuticals Cluster

Tel: +41.22.791.3598 Fax: +41.22.791.4730World Health Organization

E-mail: hietavam@who.int

Basic Principles of GMP

Part One, 14

WHO - PSM

Materials

Objectives To review specific requirements for each type of

material: Starting materials Packaging materials Intermediate and bulk products Finished products Rejected and recovered materials Recalled products Returned goods Reagents and culture media Reference standards Waste materials Miscellaneous materials.

To examine (in groups) the problems associated with materials, and how to overcome them.

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Materials

Principle Objective of the pharmaceutical manufacturer:

produce finished products from a combination of materials

Materials combined: active pharmaceutical ingredients auxiliary materials (excipients) packaging materials

Special attention: specified materials, specified quality of materialsIF NOT rejected or recalled lost money, lost time

Part One 14.1–14.2

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Part One 14.3–14.5

MaterialsGeneral requirements for materials

All incoming materials and finished products quarantined after receipt,

– until released for use– distribution

stored– under appropriate conditions– orderly fashion (batch segregation)– materials management– stock rotation (FIFO or EEFO)

Materials for cleaning, lubrication of equipment, pest control No direct contact with the product Should be of suitable grade minimise health risks

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Part One 14.3–14.5

MaterialsGeneral requirements for materials

Materials for cleaning, lubrication of equipment, pest control No direct contact with the product Should be of suitable grade minimise health risks

Water Suitable for the intended use

– Sterile– Non-sterile– laboratory

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Part One 14.7–14.10

Materials

Starting Materials – I Purchasing

Competent personnel; regulatory affairs Suppliers

Approved suppliers Quality agreement: critical aspects, specifications,

rejection,complaint and recall procedures Consignment

integrity seal order delivery note supplier’s labels

Cleaned and labelled

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Part One 14.11–14.14

Materials

Starting Materials – II Damaged containers

Different batches in one consignment

Starting material label: name and internal code batch number(s), (supplier and manufacturer on

receipt) status expiry date or re-test date

Sampled containers identified

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Materials

Starting Materials – III Identification

every container Identification of sampled container

Release Only released materials within their shelf-life should

be used

Part One 14.14–14.15

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Materials

Examples of Labelling of Starting Materials

Name ofMaterial and/ orinternal codeControl/Batch No.

StatusQuarantined/Released/Rejected

(Colors may be used)Expiry date orretest dateDate Signature

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Part One 14.16–14.18

Materials

Starting Materials – III Dispensing:

designated persons written procedure accurately weighed clean, labelled containers

Independent checks material and weight

Dispensed material: kept together and labelled

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Part One 14.19–14.20

Materials

Packaging materials I Primary and printed materials:

as for starting materials– purchasing, handling and control

No unauthorized access

Storage and transport avoid mix-ups: sealed containers!! issue and return: SOP Note: storage and responsible persons of printed

packaging material in production!

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Part One 14.21–14.23

Materials

Packaging materials II

Specific reference number for batch or consignment

Packaging department checks quantity, identity and conformity

Outdated or obsolete material

Printed packaging material reconciliation

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Part One 14.24–14.25

Materials

Intermediate and bulk products

Appropriate conditions Controlled and tested (or validated) Appropriate time (tested or validated) Sampling should not have negative affect (cross-

contamination, contamination) Purchased:

as starting materials

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Part One 14.26–14.27

Materials

Finished products

Quarantine until released

Storage conditions

Evaluation product release of manufacturing documentation QC certificate of analysis other documentation (environmental control) authorised person

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Part One 14.28–14.29 and 14.31

Materials

Rejected and recovered materials

Rejected materials Clearly marked Stored separately in restricted areas Action

Reprocessing: exceptional procedure and records batch number additional testing

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Part One 14.30–14.31

Materials

Rejected and recovered materials

Recovery only exceptional!! prior authorization!!!! additional testing accurate documentation

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Part One 14.32–14.33

Materials

Recalled products and returned goods Recalled products:

identified stored separately access controlled fate

Returned goods: SOP: decision regarding the fate nature of product, storage conditions history, time lapse records

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Part One 14.34–14.36

MaterialsReagents and culture media

Recorded upon receipt or preparation

Reagents: preparation in accordance with SOP label:

– concentration, standardisation factor, shelf-life, date that re-standardisation is due, storage conditions

– signed and dated

Culture media: positive and negative controls

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Part One 14.37–14.40

MaterialsReference standards-I

Official reference standards use only as per monograph storage

Reference standards prepared by the producer: tested, released stored in same way as official reference standards

Secondary or working standards: appropriate checks and tests regular intervals based on official reference standards

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Part One 14.41–14.43

Materials

Reference standards-II Labelling of reference standards

minimum information In-house standards

standardised against an official reference standard– when available– Initially and at regular intervals thereafter

Storage quality maintained

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Part One 14.44–14.46

Materials

Waste materials and miscellaneous materials

Waste materials proper and safe storage toxic and flammable materials

– separate, enclosed, as per legislation not allowed to accumulate

– collected for safe disposal– regular intervals

Miscellaneous rodenticides, insecticides, sanitizing material contamination risks