Materials/Standards

GMP course, 17-18 Jan, 2006

Supaporn Phumiamorn
Division of Biological Products
Type of materials
 Starting materials
 Packaging materials
 Intermediate and bulk materials
 Finished products
 Rejected and recovered materials
 Returned goods
 Recalled products

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  Reagent and culture media
 Reference standards
 Waste materials
 Miscellaneous materials

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General requirements for materials

 All incoming materials and

finished products
- quarantined after receipt
- until release for use
- distribution

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General requirements for materials

 Stored
- under appropriate condition
-orderly fashion (batch segregation)
- materials management
-stock rotation (FIFO, FEFO)

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 General requirements for materials

• Documentation
- SOPs
- Records
- Labels
- Specifications

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Starting materials
 Purchasing
 Suppliers
 Consignment
- integrity - delivery note
- seal - supplier’s label
- order
 Cleaned and labeled

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Starting materials
 Damaged containers
 Starting materials label:
- name and internal code
- batch number
- status
- expiry date or re-test date
 Sample container identified

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Starting materials
 Use only released material
 Dispensing
- designated persons
- written procedure
- accurately weighed
- clean, labeled containers

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Starting materials

 Independent checks
- material and weight
 Dispensed material
- kept together and labeled

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 Why starting materials
are so important?

Because their quality can directly

affect the quality of finished
products

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Packaging materials
 Primary and printed materials:
- as for starting materials
purchasing, handing and control
 No unauthorized access
 Storage and transport
- avoid mix-ups
- issue and return: SOP

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Intermediate and bulk products

 Appropriate conditions

 Purchased:
-as starting materials

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Finished products
 Quarantine until released

 Storage conditions

 Evaluation and documentation

- product release

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Rejected and recovered materials

 Rejected materials
- clearly marked
- stored separately in restricted
areas
- take action rapidly

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  Reprocessing
- exceptional
- procedure and records
- batch number
- additional testing

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  Recovery
- prior authorization
- additional testing

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Recalled products and returned
goods

 Recalled products
- identified
-stored separately
- access controlled

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

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 Reagents and culture media
 Record upon receipt or preparation
 Reagents:
- preparation in accordance with SOP
- label:
- concentration, shelf-life, storage conditions
- signed and dated

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  Culture media:
- positive and negative
controls

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Reference Standard

 Standard must be stable

 Sufficient standard must be
available for several years

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

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 WHO Expert Committee on Biological
Standardization (ECBS)

 One of the oldest WHO committees

 Began as a mechanism for developing
primary biological standards
 Meet each year in Geneva
 Members chosen from the Expert Advisory
Panel
 Reports published in WHO Technical Report
Series
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 WHO Expert Committee on Biological
Standardization (ECBS)
 Purpose
- To establish primary biological standards
- To prepare written guidance on production
and quality control of biological medicinal
products
- To develop international consensus on issues
of quality, safety and efficacy related to
biological products

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Biological reference materials

 Standard and test must be similar in

composition and behave in the same
way in the test system
 Standard does not have to be pure
 Standard must have potency value
assigned

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 Calibration System

WHO: Calibration is generally achieved by

parallel titration on at least six
separate occasions.
NCL: Calibration is routinely performed at
least six times by at least two persons.
(2 NCL labs + Manufacturer lab)

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Calibration of WRP for Total OPV

(Measles, Mumps, Rubella)

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 Parallel line assay
Parallelity
Response

Linearity

95% confidence limit

Probit analysis

Dose
(JE, Rabies ,Hepatitis B, Pertussis vaccines)
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 Reference Standard materials

assuring the uniformity of the testing results

assuring the reliability of the testing results

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 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

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  Miscellaneous
- rodenticides, insecticides,
sanitizing materials
- contamination risks

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Materials checklist
 Quarantine
 Storage condition
 Purchasing
 Labelling
 Use of release material
 Printed packaging material
 Purchasing of intermediate or bulk

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Materials checklist
Records of the original and history of
seeds/ banks and etc.

Specifications for biological additives

-Trypsin is mycoplasma free
- Fetal calf serum if from BSC free animals

Certificate of analysis from the supplier

Records of audit of supplier

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Warehouse area
 Entering
 Sufficient capacity
 Good storage conditions
 Sanitation program
 Receiving and dispatch bays
 Quarantine areas
 Sampling areas
 Segregation

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Warehouse area
 Highly active and hazardous materials
 Handling and distribution
 Contanmination and cross-contamination
 The First Expired/First Out (FEEO)
 Rejected materials
 Narcotic
 Damaged items

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Warehousing and Distribution
Products

Quarantine

Quality control

Release - FIFO
- FEFO
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Storage conditions
 Stability
 Monitoring
- Check and record
- Records
- Equipment calibration

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Documentations and records
 SOPs and Records
 Written information
 Container’s label
- Name
- Lot number
- Shelf life
- Storage conditions

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 Receipt of incoming materials
 Check against the relevant purchase order
 Uniformity
 Container inspection
 Record should be retained for each
delivery
 Sampling
 Quarantine and batch segregation
 Written release or rejection
 Rejected materials cannot be used
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Stock rotation and control
 Comprehensive records
 Periodic stock reconciliation
 Significant stock discrepancies
 Re-close and reseal
 Damaged containers
 Outdate materials

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Dispatch and transport
 Integrity
 Special care for dry ice
 Delivery order
 Rules for dispatch
 The outside container
 Monitor conditions during
transportation

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Warehouse check list
Identification of all customers

Records of storage: time, temperatures

Records of date, quantity, mode of packaging

Distribution to customer
SOPs for storage of released products

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 SOPs for warehousing

SOPs for shipping, final transit conditions

and storage

Validation and monitoring of shipping methods

Recalled

Maintenance of records for 2 years beyond

Expiry date
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 References
 WHO,1997. Joint training on GMP for biological
products in Thailand, 2-11 September, 1997
 Chung Keel Lee, 2003. GMP and related topics, 13-15
October, 2003.
 Chung Keel Lee, 2004. Current GMP for biological
products and its practical implementation, 22-23
March, 2004.
 FDA and WHO, 2004. GMP inspection workshop, 21-
29 June, 2004.

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