著者

Kazuya YOSHIDA S.L. IRISHI J. A. BOOSE

出版者

Parenteral Drug Association Japan Chapter

雑誌

日本PDA学術誌 GMPとバリデーション (ISSN:13444891)

巻号頁・発行日

vol.1, no.2, pp.71-76, 1999 (Released:2006-08-03)

参考文献数

7

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Viral spiking studies were used to validate the capacity of our manufacturing process of a biological product derived from animal origin to inactivate or eliminate potential viral contaminants. Since the present study was intended for early Phase I & II clinical trials, two model viruses, Xenotropic Murine Leukemia Virus and polio virus, type 1, which represent a range of physical, chemical, and biological properties were selected for examination. It is generally recommended to take at least two different viral inactivation removed procedures for the robustness of the manufacturing process. We therefore selected a heat treatment and an ethanol purification step, two steps which held the potential for inactivation through independent mechanisms (i.e., physical and chemical inactivation, respectively). Finally, with the design of the experiment taken into consideration, the manufacturing steps were scaled-down and validated. Further, based upon the data collected during validation, the step parameters used for the present study were considered worst-cases. The result of the present spiking study for the two steps was a combined reduction of > 11 logs for polio virus and > 8 logs for X-MuLV which was the maximum attainable clearance given the spiking titer and dilution level for both viruses and both manufacturing steps.