Biological Product Safety: Assay development for latent viruses in vaccine cell substrates and risk assessment of retrovirus transmission
Principal Investigator: Arifa S. Khan, PhD
Office / Division / Lab: OVRR / DVP / LR
Overview
Public Health Issue: Biological products for human use must be demonstrated to be free of infectious virus. Retroviruses and some DNA viruses can persist in the host in a latent state and become activated resulting in disease. Virus contamination of biological products can occur due to: 1) the donor species or passage history of the cell substrate; 2)activation of latent viral sequences in the cell substrate due to the manufacturing procedure; or 3) by inadvertent introduction of exogenous viruses that may be present in the raw biological materials used in manufacture, e.g. animal or human serum and animal trypsin. Therefore, when products are derived from or manufactured in components of human or animal origin, it is critical to demonstrate the absence of viruses by extensive testing at various stages of production to assure product safety. The risk of inadvertent infection with viruses in biologicals is an important safety concern especially in live viral vaccines, gene therapy vectors and transfused whole blood, where there are no virus inactivation or removal steps that can eliminate known or unknown infectious agents and still assure full product potency.
Regulatory Contribution: Development of new products have necessiated the use of novel cell substrates. Development and standardization of sensitive assays for detection of known and novel viruses will help demonstrate the safety of novel cell substrates and facilitate safe product use. Determining the risk of human infection with viruses of concern in biological products will enhance public confidence in product safety.
Research Approach: This research program develops and evaluates sensitive, state-of-the-art assays for detection of exogenously acquired and latent viruses in vaccine cell substrates, which includes establishing relevant cell controls for virus activation/induction studies. Additionally, the program investigates the risk assessment of retroviruses that may be a safety concern in biological products such as blood and blood products.
Mission Relevance and Outcomes: The development of sensitive assays for demonstrating absence of adventitious viruses in biological products improves risk assessments and supports product safety, which is a major goal of CBER/FDA. Investigation and evaluation of the risk of human infection by viruses of potential concern in biological products provides a scientific basis for testing recommendations and regulatory policy development.
Publications
Transfusion 2006 Aug;46(8):1352-9
Simian foamy virus infection by whole-blood transfer in rhesus macaques: potential for transfusion transmission in humans.
Khan AS, Kumar D
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