materials rutendo kuwana technical officer, who, geneva training workshop: training workshop on...

Materials

Rutendo Kuwana

Technical Officer, WHO, Geneva

Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda.

Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 2 |

Basic Principles of GMPBasic Principles of GMP

Materials

14


MaterialsMaterials

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


MaterialsMaterials

Principle

Objective of the pharmaceutical manufacturer produce finished products for patient's use from a

combination of materials

Materials combined Active pharmaceutical ingredients and Excipients (auxiliary materials) Packaging materials

Materials include also Gases, solvents, reagents, process aids, etc. Special attention 14.1, 14.2


14.3–14.6

MaterialsMaterials

General requirements for materials

Materials for cleaning, lubrication, and pest control Not in direct contact with product Suitable grade, e.g. food grade if possible

All incoming materials and finished products quarantined after receipt or processing

– until released for use or distribution stored

– under appropriate conditions– orderly fashion (batch segregation)– materials management– stock rotation (FEFO)

Water – suitable for use


14.7 – 14.10

MaterialsMaterials

Starting Materials – I

Purchasing – important operation From approved suppliers – if possible, direct from the

manufacturerSpecifications for materialsConsignment checks

Integrity of package Seal intact Corresponds with the purchase order Delivery note Supplier’s labels

Cleaned and labelled with information


Supplier EvaluationSupplier Evaluation

Historical experience

Questionnaire – including reputation within industry, availability of certificates e.g. ISO 9000 certificates, GMP

Check/compare own analytical results e.g. three batches/shipments with suppliers CoA

Site audit of supplier (case by case basis)

Name and address of manufacturer of critical material must always be known

Changes in source (manufacturer or supplier) of critical material should be handled according to Change Control procedure


14.11 – 14.14

MaterialsMaterials

Starting Materials – II

Different batches in one delivery/consignment

Starting materials labelled name and internal code Supplier's batch number(s) and manufacturer's on receipt Status (e.g. quarantine, on test, etc.) expiry date or retest date

Role of validated computer systems

"Sampled" containers identified


Sampling and TestingSampling and Testing

Sampling plans should be scientifically sound (not just statistically based) and appropriate for material being sampled.

They must also be practical/easy to use - obtain a representative sample

Should be based on Risk Assessment

• Criticality of the material

• Manufacturers/suppliers quality system and manufacturing process

• Historical data

• Homogeneity



Damage to and problems with containers Recorded and reported

to QC Investigated


MaterialsMaterials

Examples of Labelling of Starting Materials

Name of Material and/ or internal code

Control/ Batch No.

Status Quarantined/Released/Rejected

(Colours may be used)

Expiry date or retest date

Date Signature


14.15 – 14.18

MaterialsMaterials

Starting Materials – III

Use only QC released material if within shelf-lifeDispensing

designated persons written procedure Correct materials accurately weighed clean, properly labelled containers

Independent checks and record material and weight or volume

Dispensed material kept together and labelled


14.25–14.20

MaterialsMaterials

Packaging materials - I

Primary and printed packaging materials purchasing, handling and control

– as for starting materialsPrinted packaging materials: particular attention

Stored in secure conditions with authorized access Roll labels where possible in place of cut labels Loose materials stored and transported in separate, closed

containers - to avoid mix-ups Issued by designated personnel SOP for issue and returns


14.21 – 14.23

MaterialsMaterials

Printed and primary packaging materials - II

Each delivery or batch: specific reference number or identification mark

Delivery to packaging department Check quantity, identity and conformity to packaging

instructions

Outdated or obsolete material Destroyed Disposal record



Intermediate and bulk products

Kept under appropriate conditions

If purchased as such Handled on receipt as

though these are starting materials

14.24 – 14.25



Finished products

Held in quarantine until their final release

Then stored as usable stock under suitable storage conditions

Evaluation and documentation necessary for release

Product release procedure

Batch record review and related procedure

14.26 – 14.27


14.28

MaterialsMaterials

Rejected, reworked and recovered materials

Rejected materials and products Clearly marked Stored separately in restricted areas Action – returned to supplier/destroyed, etc. in timely manner Action approved by authorized personnel – records

maintained


14.29 – 14.30

MaterialsMaterials

Rejected, reworked and recovered materials

Rework and recovery Should be exceptional cases Only if:

– Risks involved have been evaluated and the quality of final product will not be affected

– Specifications are met– Defined procedure– Records maintained– New batch number

additional testing to be considered by QC


14.32 – 14.33

MaterialsMaterials

Recalled products and returned goods

Recalled products Identified Stored separately Secure area - access controlled Decision taken on their fate

Returned goods Destroyed unless suitable quality SOP: decision regarding their fate (relabelling, resale, etc.)

– Consider: nature of product, special storage conditions, condition, history, time elapsed since issue

Action taken to be recorded


14.34 – 14.36

MaterialsMaterials

Reagents and culture media

Records for receipt or preparationReagents

Preparation in accordance with SOP Appropriately labelled:

– concentration, standardization factor, shelf-life, date that restandardization is due, storage conditions

– signed and datedCulture media

positive and negative controls each time prepared and used Inoculum size appropriate


14.37 – 14.40, 14.42

MaterialsMaterials

Reference standards - I

Official reference standards Use preferable whenever these exist Only for the purpose as per monograph Storage conditions

Reference standards prepared by the producer Tested, released and stored in the same way as official

standards In a secure area A responsible person

Secondary or working standards Appropriate checks and tests at regular intervals Standardized against official reference standards – initially and

at regular intervals


14.41, 14.43

MaterialsMaterials

Reference standards - II

Reference standards labelled with information including Name Batch, lot or control number Date of preparation Shelf-life Potency Storage conditions

Stored and used in an appropriate manner


14.44

MaterialsMaterials

Waste materials

Waste materials proper and safe storage when awaiting disposal toxic substances and flammable materials:

– in suitably designed, separate, enclosed areas as per national legislation

not to be allowed to accumulate– collected in suitable containers for removal to collection

points– safe and sanitary disposal– regular and frequent intervals


14.45

MaterialsMaterials

Miscellaneous materials

Miscellaneous Rodenticides, insecticides, fumigating agents Sanitizing material No contamination risk to equipment, starting materials,

packaging materials, in-process materials, finished products


MaterialsMaterials

Group session

List specific aspects of GMP requirements, in relation to the groups of materials listed below, that you would assess when inspecting a manufacturer Printed packaging materials Thermolabile materials Water Sterile materials

Identify three materials that present problems in your experience

What are some of the problems that you have experienced before and during inspection of materials?

materials rutendo kuwana technical officer, who, geneva training workshop: training workshop on...

Documents

incoming materials

materials objectives

materials general requirements

materials principle

combined medicines

use slide

registration of artemisinin

information slide