Alcanos y alquenos

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History and Characterization of the Vero Cell Line
A Report prepared by CDR Rebecca Sheets, Ph. D., USPHS CBEFVOVRFVDVRPANVB

for the Vaccines and Related Biological Products Advisory Committee Meeting to be held on May 12,2000

OPEN SESSION
AVAILABLE IN THE PUBLIC DIOMAIN —

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Introduction
CBER is requesting expert advice from the Vaccines and Related BiologicalProducts Advisory Committee (VRBPAC) upon the use of Vero cells for the production of viral vaccines. To provide you with information upon which to consider your feedback, confidential information about products under review in Investigational New Drug Applications (INDs) has been provided to you under separate cover. In addition, below you will find a summary about the published history andcharacterization of Vero cells, as well as a brief description of the tests recommended by CBER for characterization of cell lines used to produce biological, as promulgated in the 1993 “Points to Consider in the Characterization of Cell Substrates Used to Produce 13iologicals” (referred to herein as the PTC) and the International Conference on Harmonisation (ICH) Q5D document entitled “Guidance on Quality ofBiotechnological/Biological Products: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products” published in the Federal Register on 9/21/98. Currently, the Vero cell line is used to produce only one U.S. licensed viral vaccine, inactivated poliovirus vaccine produced by Aventis Pasteur. However, CBER has received proposals either in pre-lNDor under IND to use Vero cells to produce many other viral vaccines, including live viral vaccines. With the exception of this one licensed inactivated and purified vaccine, all other licensed vaccines are produced in diploid cell strains (WI-38, MRC-5, FRhL-2), yeast, or prinnary cells (eggs, primary monkey kidney cells) which are considered “normal.” In contrast, the Vero cell line is acontinuous cell line, which is aneuploid and will grow indefinitely in culture. At the passage levels used for vaccine manufacture, Vero cells do not form tumors in rodents. However, these cells are nc)t “normal” diploid cells used to immunosuppressed produce other types of licensed viral vaccines. Concerns over use of “normal” or “abnormal” cells are described in literature cited in the attachedbibliography and will not be discussed herein. However, the committee may wish to consider these concerns, as similar issues are of current concern regarding continuous cell lines as were considered for human diploid cell strains historically. This is reviewed in two of the articles cited in the bibliography below and provided to the committee.

Mit!2!Y
The Vero cell line was derived from the kidney ofa normal, adult, African green monkey (Cercopithecus) on March 27, 1962, by Y. Yasumura and Y. Kawakita at the Chiba University in Japan (Nippon Rinsho 21:1209, 1963). The cell line was brought to the Laboratory of Tropical Vkology, NIAID, NIH, at passage Ilevel 93 from Chiba University by Dr. B. Simizu on June 15, 1964. There is documentation of the types of culture media and the concentration ofbovine serum used in the media throughout its history. In addition to its use as a vaccine cell substrate, this cell line has been used extensively for virus replication studies and plaque assays. Vero cells are sensitive to infection with SV-40, SV-5, measles, arboviruses, reoviruses, rubella, simian adenoviruses, polioviruses, influenza viruses, parainfluenza viruses, respiratory syncytialviruses, vaccinia, and others. The cell line was submitted to the ATCC at passage level 113 and

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was propagated to passage level 121 at the ATCC to establish a bank of cells for availability. Thus, most vaccine manufacture is performecj with cells at passage levels in the 130’s or 140’s, after further propagation for establishment of manufacturer’s master and working cell banks and...