materials gmp

Materials/Standards

Supaporn PhumiamornDivision of Biological Products

GMP course, 17-18 Jan, 2006

Supaporn Phumiamorn,GMP course 17-18 Jan,2006 2

Type of materials

Starting materials Packaging materials Intermediate and bulk materials Finished products Rejected and recovered materials Returned goods Recalled products


Reagent and culture media Reference standards Waste materials Miscellaneous materials


General requirements for materials

All incoming materials and finished products- quarantined after receipt

- until release for use - distribution


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



• Documentation

- SOPs- Records- Labels- Specifications



Starting materials Purchasing Suppliers Consignment

- integrity - delivery note- seal - supplier’s label- order

Cleaned and labeled


Damaged containers Starting materials label:

- name and internal code- batch number- status- expiry date or re-test date

Sample container identified

Starting materials


Use only released material Dispensing

- designated persons- written procedure- accurately weighed- clean, labeled containers

Starting materials


Independent checks- material and weight

Dispensed material- kept together and labeled

Starting materials


Why starting materials are so important?

Because their quality can directly

affect the quality of finishedproducts


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


Intermediate and bulk products

Appropriate conditions

Purchased:-as starting materials


Finished products

Quarantine until released

Storage conditions

Evaluation and documentation- product release


Rejected and recovered materials

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


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


Recovery- prior authorization- additional testing


Recalled products and returned goods

Recalled products- identified-stored separately- access controlled


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


Reagents and culture media

Record upon receipt or preparation Reagents:

- preparation in accordance with SOP- label:

- concentration, shelf-life, storage conditions

- signed and dated


Culture media:- positive and negative controls


Standard must be stable Sufficient standard must be

available for several years

Reference Standard


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


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


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

WHO Expert Committee on Biological Standardization (ECBS)


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


Calibration System

WHO: Calibration is generally achieved by parallel titration on at least six separate occasions.

NCL: Calibration is routinely performed atleast six times by at least two

persons. (2 NCL labs + Manufacturer lab)


Calibration of WRP for Total OPV

กราฟแสดงผลการสอบเที�ยบOPV: Total

6.2

6.4

6.6

6.8

7

1 2 3 4 5 6ครั้��งที่��

log CCID50/ dose Potency

Mean

Mean+2SD

Mean-2SD

Mean+3SD

Mean-3SD

(Measles, Mumps, Rubella)


Parallel line assayR

esp

onse

Dose

Parallelity

Linearity

95% confidence limit

Probit analysis

(JE, Rabies ,Hepatitis B, Pertussis vaccines)


Reference Standard materials

assuring the uniformity of the testing results

assuring the reliability of the testing resultsassuring the reliability of the testing results


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 materials- contamination risks


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


Materials checklistRecords 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


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


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

Warehouse area


Warehousing and Distribution

Products

Quarantine

Quality control

Release - FIFO- FEFO


Storage conditions

Stability Monitoring

- Check and record- Records- Equipment calibration


Documentations and records

SOPs and Records Written information Container’s label

- Name- Lot number- Shelf life- Storage conditions


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


Stock rotation and control

Comprehensive records Periodic stock reconciliation Significant stock discrepancies Re-close and reseal Damaged containers Outdate materials


Dispatch and transport

Integrity Special care for dry ice Delivery order Rules for dispatch The outside container Monitor conditions during

transportation


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


SOPs for warehousing

SOPs for shipping, final transit conditions and storage

Validation and monitoring of shipping methods

Recalled

Maintenance of records for 2 years beyondExpiry date


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.

materials gmp

Documents

starting materials

materials label

bulk materials

printed materials

incoming materials

type of materials

materials checklist

packaging materials