This document outlines testing guidelines for vaccine production in the USA. It discusses testing that should be done at various stages of production including characterization of master and working cell banks, virus bulk harvests, and final product testing. A wide range of tests are recommended to evaluate morphology, identity, sterility, mycoplasma levels, adventitious agents, potency, and safety.

1. Vaccine in USA
Draft Guidance for Industry
Characterisation of Production Control Characterisation of
Final Product Testing
MVSS/MCB Cell Testing Virus Bulk Harvests
Master Cell Bank Working Cell Bank End of production bank MVSS Testing
• Morphology – light • Morphology – light • Morphology – light • Observation/Morphology • Sterility • Sterility
• Identity using appropriate
microscopic observations microscope observations microscopic observations • in vitro adventitious virus test • Mycoplasma/ Spiroplasma • Mycoplasma/Spiroplasma
methods
• Identity – DNA Fingerprinting • Identity – DNA Fingerprinting • Identity – DNA Fingerprinting • in vivo adventitious virus test • Mycobacterium • General Safety
• Sterility (21 CFR 610.12)
• Sterility (21 CFR 610.12) • Sterility (1% of cell bank) • Sterility (21 CFR 610.12) • Haemadsorbtion • Appearance • Identity
• Mycoplasma test
• Mycoplasma test • Mycoplasma test • Mycoplasma test • Mycoplasma/Spiroplasma • Identity • Appearance
• Infectious titre
• in vivo – Adult and Suckling • in vivo – Adult and Suckling • tests in adult and suckling • Sterility • Potency/Infectious titre • Residual Host Cell Protein
mice, Guinea Pigs, Rabbits, eggs mice, Guinea Pigs, Rabbits, eggs mice, embryonated chickens • Species specific viruses • RT Assay • Residual Host cell DNA
• Transmission Electron • Transmission Electron eggs and Guinea Pigs • Mycobacteria • 14 Day in vitro – MRC-5, • Potency
Microscopy Microscopy • in vitro/haemagglutinating Vero and cells of same
• RT Assay • Osmolality
• Bovine viruses following • Bovine viruses following virus test using Simian and species and tissue type as
methods outlined by 9CFR methods outlined by 9CFR Human cells • Bovine viruses following the production cells • Residual Serum, antibiotics etc.
113.53 and 113.47 113.53 and 113.47 methods outlined by 9CFR • pH
• RT assay 113.53 and 113.47 • in vivo assay in adult
• Porcine viruses following • Porcine viruses following • Bovine viruses following and suckling mice and • Bacterial endotoxins
methods outlined by 9CFR methods outlined by 9CFR • Porcine viruses following embryonated chickens eggs
methods outlined by 9CFR methods outlined by 9CFR
113.53 and 113.47 113.53 and 113.47 113.53 and 113.47 • Bovine viruses following
113.53 and 113.47
• tests for specific agents using • tests for specific agents using • Porcine viruses following methods outlined by 9CFR
antibody production tests antibody production tests methods outlined by 9CFR 113.53 and 113.47
• tests for specific agents using • tests for specific agents using 113.53 and 113.47 • Porcine viruses following
PCR tests PCR tests • Mycobacterium methods outlined by 9CFR
• RT Assay • RT Assay 113.53 and 113.47
• Mycobacterium • Mycobacterium
• Infectivity tests for Retroviruses • Infectivity tests for Retroviruses
• In vitro tests for viruses using • In vitro tests for viruses using
Monkey Kidney, Human diploid Monkey Kidney, Human diploid
and cultures of the sames and cultures of the sames
species and tissue type as the species and tissue type as the
production cells production cells
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