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.
 Basic Principles of GMP

Materials

14

Artemisinin based combined medicines

2| February 23-27, 2009, Kampala, Uganda
 Materials
Objectives
 To review specific requirements for each type of material:
ä Starting materials
ä Packaging materials
ä Intermediate and bulk products
ä Finished products
ä Rejected and recovered materials
ä Recalled products
ä Returned goods
ä Reagents and culture media
ä Reference standards
ä Waste materials
ä Miscellaneous materials

Artemisinin based combined medicines

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 Materials
Principle
 Objective of the pharmaceutical manufacturer
ä produce finished products for patient's use from a
combination of materials

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

 Materials include also

ä Gases, solvents, reagents, process aids, etc.
ä Special attention 14.1, 14.2

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 Materials
General requirements for materials
 Materials for cleaning, lubrication, and pest control
ä Not in direct contact with product
ä Suitable grade, e.g. food grade if possible
 All incoming materials and finished products
ä quarantined after receipt or processing
– until released for use or distribution
ä stored
– under appropriate conditions
– orderly fashion (batch segregation)
– materials management
– stock rotation (FEFO)
 Water – suitable for use 14.3–14.6

Artemisinin based combined medicines

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 Materials
Starting Materials – I
 Purchasing – important operation
 From approved suppliers – if possible, direct from the
manufacturer
 Specifications for materials
 Consignment checks
ä Integrity of package
ä Seal intact
ä Corresponds with the purchase order
ä Delivery note
ä Supplier’s labels
 Cleaned and labelled with information 14.7 – 14.10

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 Supplier 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
Artemisinin based combined medicines
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 Materials
Starting Materials – II
 Different batches in one delivery/consignment

 Starting materials labelled

ä name and internal code
ä Supplier's batch number(s) and manufacturer's on receipt
ä Status (e.g. quarantine, on test, etc.)
ä expiry date or retest date
Role of validated computer systems

 "Sampled" containers identified

14.11 – 14.14

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 Basic Principles of GMP

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 Sampling 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

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 Basic Principles of GMP

 Damage to and problems

with containers
ä Recorded and reported
to QC
ä Investigated

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 Materials
Examples of Labelling of Starting Materials

Name of
Material and/or
internal code
Control/
Batch No.
Quarantined/Released/Rejected
Status
(Colours may be used)
Expiry date or
retest date
Date Signature

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 Materials
Starting Materials – III
 Use only QC released material if within shelf-life
 Dispensing
ä designated persons
ä written procedure
ä Correct materials accurately weighed
ä clean, properly labelled containers
 Independent checks and record
ä material and weight or volume
 Dispensed material
ä kept together and labelled
14.15 – 14.18

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 Basic Principles of GMP

Artemisinin based combined medicines

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 Materials
Packaging materials - I
 Primary and printed packaging materials
ä purchasing, handling and control
– as for starting materials
 Printed packaging materials: particular attention
ä Stored in secure conditions with authorized access
ä Roll labels where possible in place of cut labels
ä Loose materials stored and transported in separate, closed
containers - to avoid mix-ups
ä Issued by designated personnel
ä SOP for issue and returns 14.25–14.20

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 Basic Principles of GMP

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 Materials
Printed and primary packaging materials - II

 Each delivery or batch: specific reference number or

identification mark
 Delivery to packaging department
ä Check quantity, identity and conformity to packaging
instructions
 Outdated or obsolete material
ä Destroyed
ä Disposal record
14.21 – 14.23

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 Basic Principles of GMP

Intermediate and bulk

products
 Kept under appropriate
conditions

 If purchased as such
ä Handled on receipt as
though these are
starting materials

14.24 – 14.25

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 Basic Principles of GMP

Finished products
 Held in quarantine until their
final release
 Then stored as usable stock
under suitable storage
conditions
 Evaluation and
documentation necessary
for release
ä Product release procedure
ä Batch record review and
related procedure
14.26 – 14.27

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 Materials

Rejected, reworked and recovered materials

 Rejected materials and products

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

14.28

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 Materials
Rejected, reworked and recovered materials

 Rework and recovery

ä Should be exceptional cases
ä Only if:
– Risks involved have been evaluated and the quality of
final product will not be affected
– Specifications are met
– Defined procedure
– Records maintained
14.29 – 14.30
– New batch number
ä additional testing to be considered by QC

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 Materials
Recalled products and returned goods
 Recalled products
ä Identified
ä Stored separately
ä Secure area - access controlled
ä Decision taken on their fate
 Returned goods
ä Destroyed unless suitable quality
ä SOP: decision regarding their fate (relabelling, resale, etc.)
– Consider: nature of product, special storage conditions,
condition, history, time elapsed since issue
ä Action taken to be recorded 14.32 – 14.33

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 Materials
Reagents and culture media
 Records for receipt or preparation
 Reagents
ä Preparation in accordance with SOP
ä Appropriately labelled:
– concentration, standardization factor, shelf-life, date that
restandardization is due, storage conditions
– signed and dated
 Culture media
ä positive and negative controls each time prepared and used
ä Inoculum size appropriate
14.34 – 14.36

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 Materials
Reference standards - I
 Official reference standards
ä Use preferable whenever these exist
ä Only for the purpose as per monograph
ä Storage conditions
 Reference standards prepared by the producer
ä Tested, released and stored in the same way as official
standards
ä In a secure area
ä A responsible person
 Secondary or working standards 14.37 – 14.40, 14.42
ä Appropriate checks and tests at regular intervals
ä Standardized against official reference standards – initially and
at regular intervals
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 Materials
Reference standards - II
 Reference standards labelled with information including
ä Name
ä Batch, lot or control number
ä Date of preparation
ä Shelf-life
ä Potency
ä Storage conditions
 Stored and used in an appropriate manner
14.41, 14.43

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 Materials
Waste materials

 Waste materials
ä proper and safe storage when awaiting disposal
ä toxic substances and flammable materials:
– in suitably designed, separate, enclosed areas as per
national legislation
ä not to be allowed to accumulate
– collected in suitable containers for removal to collection
points
– safe and sanitary disposal
– regular and frequent intervals
14.44

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 Materials
Miscellaneous materials

 Miscellaneous
ä Rodenticides, insecticides, fumigating agents
ä Sanitizing material
ä No contamination risk to equipment, starting materials,
packaging materials, in-process materials, finished products

14.45

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 Materials
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
ä Printed packaging materials
ä Thermolabile materials
ä Water
ä 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?

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