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Definition
In order to prevent the unwanted drift of properties which might ensue from repeated subcultures or multiple generations, the production of biological medicinal products obtained by microbial culture, cell culture or propagation in embryos and animals should be based on a system of master and working seed lots and/or cell banks.
GMP
Media/Cell culture
Excipients Validation - process - method Stability studies
Single harvest
Importance of Seed
Safe Seed
Good product
Potent
Seed
Cost Benefit
Seed
To have Safe, Pure and effective products To have valid QC test To compliance with cGMP Permanent production To have Good R&Ds Security
2.
3.
The fabrication of biological product is based on a system of master and working seed lots and cell banks. Seed lots and cell banks are established in a suitably controlled environment to protect the seed lot or the cell bank and the personnel. Seed lots and cell banks are characterized according to ICH Q5D and maintained in such a way as to minimize the risks of contamination or alteration.
The stability of seed lots and cell banks is documented, including the efficiency of recovery. Storage containers are appropriate to their function ( Storage containers should be hermetically sealed), clearly labeled (Barcode) , and kept at a suitable temperature. Storage temperatures are properly monitored. Deviations from set limits and any corrective actions are evaluated and documented.
6. 7.
8.
Only authorized personnel under the supervision of a responsible person, may handle seed lots and cell banks. An inventory is meticulously kept. (FIMS) A system is in place to ensure security and retrievability of seed lot or cell bank vials, without confusion or cross-contamination. All vials of master or working cell banks that removed from storage, are not returned.
2.
3.
The cell bank system consists of two tiers: a master cell bank (Master cell bank established from single clone) (MCB); and a working cell bank (WCB). should stored the MCB and WCB in two or more separate locations within the facility. To reduce the possibility of phenotypic variations, genetic drift, and contamination as much as possible, the number of passages should be minimized (five passages ) .
Master chart.doc Master seed felow chart.doc
4.
Extensive characterization of the MCB Because all WCBs would be derived from the well-characterized MCB.
ND vaccine
OIE
EP
Purity
CFR
1.Bacteria and fungi 1.Bacteria 2.Mycoplasma 2.Mycoplasma 3.Avian origin vaccine 3.Avian Salmonella contamination Lymphoid leukosis HemagglutinatingExteraneous viruses 4.Extraneous viruses 4.Extraneous by the chicken embryo inoculation test by the chicken inoculation test
Seed
Pathogenicity
Safety Identity
1.Fluorescent antibody test 1.Fluorescent 2.Serum neutralization test 2.Serum Cell culture requirements
Stability Immunogenicity
Final product
Safety Potency
By HA Or cell cultures Or fertilised hen eggs Extraneous viruses 1.using cell cultures 1.using 2.using fertilised eggs 2.using 3.using chicks 3.using 4.Avian leucosis viruses 4.Avian
Purity 1.Bacteria and fungi 1.Bacteria 2.Mycoplasma 2.Mycoplasma 3.Avian origin vaccine 3.Avian Salmonella contamination Lymphoid leukosis Hemagglutinating Extraneous viruses 4.Extraneous viruses 4.Extraneous By the chicken inoculation test By the chicken embryo inoculation test Safety Virus titer
2.
3.
ICH Q5D: Derivation and Characterization of Cell Substrates Used for Production of Biotechnology/Biological Products. ICH Q5A: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin. ICH Q5B: Quality of Biotechnology Products: Analysis of the Expression Construct in Cells Used for Production of R-DNA Derived Proteins. 21 CFR 610.18
Manufacturers should describe the type of banking system used. size of the cell bank, container, preparation, storage Manufacturers should describe their cell banking procedures. Manufacturers should describe the procedures used to avoid microbial contamination and crosscontamination by other cell types present in the laboratory. documentation system, labelling system, storage and recovery
from storage (FIMS).
Identity Test Purity Test Safety Test Stability Test Tumorigenicity Test