贵州省委贵州省69.pptVIP

Adventitious Agent Testing of Novel Cell Substrates for Vaccine ManufactureArifa S. Khan, PhD.Division of Viral ProductsOffice of Vaccines Research and ReviewCBER, FDANovember 16, 2005;Outline Cell substrates used in U.S. licensed viral vaccines Safety concerns and challenges for testing novel cell substrates, especially tumorigenic cells FDA experience with tumorigenic cell substrates Testing recommendations for novel and tumorigenic cell substrates, such as Madin-Darby canine kidney (MDCK) cells;Types of Cell Substrates Used in Current U.S. Licensed Viral Vaccines;U.S. Licensed Viral Vaccines:Primary Cells or Tissues;U.S. Licensed Viral Vaccines:Diploid Cell Strains;Viral Vaccines:Continuous Cell Lines;Transition to Novel Cell Substrates Continues…;Health of the tissue donor Viruses in donor species naturally-occurring: endogenous and exogenous viruses specific exposure (e.g. animal vaccines) Cell growth increased susceptibility for virus infection and replication provide broader host range to different viruses Cell passage history propagation in different labs biological reagents used (sera, trypsin, others) other cell lines or viruses grown at same time facilities Cell phenotype (Non-tumorigenic vs. Tumorigenic) endogenous retroviruses latent DNA viruses oncogenic viruses;FDA Experience with Tumorigenic Cells-I;;ADVENTITIOUS VIRUS TESTING OF MDCK CELLS;Comprehensive testing regimens for detection of  known and unknown adventitious viruses in  novel vaccine cell substrates should be  designed to minimize the risk of virus  contamination in vaccines, thereby assuring  product safety.; ;Adventitious Virus Testing 1993 Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals;Adventitious Virus Testing1993 Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals;Adventitious Virus TestingPotential Viruses of Safety Concern in MDCK Cells (Due to Naturally-Occurring Viruses);Adven