Medical Product Purity: Maintaining Biologics and Other FDA-regulated Products Free of the Infectious Agents of Transmissible Spongiform Encephalopathies (TSE Agents or Prions)

Principal Investigator: David M. Asher, MD
Office / Division / Lab: OBRR / DETTD / LBPUA

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Overview

Public Health Issue: In the past, TSE agents have contaminated a variety of products in classes regulated by FDA and other US government agencies, including foods, animal feeds, animal vaccines, human-derived hormones, transfused human blood, transplanted human tissues (cornea and brain membrane), and surgical devices. The contaminated products caused fatal infections, including human infections with the agent of mad cow disease.

Regulatory Contribution: Careful control of the purity of human-derived and animal-derived source materials for further manufacture and use of manufacturing processes that inactivate or remove the TSE agents can markedly reduce the risk of accidentally transmitting TSEs through contaminated products.

Research Approach: The research evaluates a variety of promising tests currently in development for detecting humans and animals silently infected with TSE agents before the onset of clinical illness--assays that might serve as screening tests to reduce the risk of using infected source materials to prepare regulated products, including vaccines and blood products. The studies also evaluate the susceptibility to infection with TSE agents of cell cultures currently in use or proposed for use to manufacture vaccines and other biologics. In addition, the program develops methods to investigate the ability of manufacturing processes, including appropriate use of practical decontamination and sterilization procedures, to eliminate the risk of TSE infectivity in final products.

Mission Relevance and Outcomes: These studies have been useful in evaluating the contributions offered by available and in-development screening tests, manufacturing processes and decontamination/sterilization techniques for maintaining abundant supplies of safe vaccines, blood products, surgical devices and other FDA-regulated products.

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Publications

J Am Assoc Lab Anim Sci 2008 Jul;47(4):64-7
Visceral and neural larva migrans in rhesus macaques.
Gozalo AS, Maximova OA, StClaire MC, Montali RJ, Ward JM, Cheng LI, Elkins WR, Kazacos KR

J Virol 2008 Jun;82(11):5255-68
Comparative neuropathogenesis and neurovirulence of attenuated flaviviruses in nonhuman primates.
Maximova OA, Ward JM, Asher DM, St Claire M, Finneyfrock BW, Speicher JM, Murphy BR, Pletnev AG

J Histochem Cytochem 2006 Jan;54(1):97-107
Computerized Morphometric Analysis of Pathological Prion Protein Deposition in Scrapie-Infected Hamster Brain.
Maximova OA, Taffs RE, Pomeroy KL, Piccardo P, Asher DM

Curr Opin Biotechnol 2005 Oct;16(5):561-7
The clearance of viruses and transmissible spongiform encephalopathy agents from biologicals.
Farshid M, Taffs RE, Scott D, Asher DM, Brorson K

J Infect Dis 2005 Apr 1;191(7):1123-8
The rat-based neurovirulence safety test for the assessment of mumps virus neurovirulence in humans: an international collaborative study.
Rubin SA, Afzal MA, Powell CL, Bentley ML, Auda GR, Taffs RE, Carbone KM

J Gen Virol 2004 Jun;85(Pt 6):1777-1784
Standards for the assay of Creutzfeldt-Jakob disease specimens.
Minor P, Newham J, Jones N, Bergeron C, Gregori L, Asher D, Van Engelenburg F, Stroebel T, Vey M, Barnard G, Head M, The WHO Working Group on International Reference Materials for the Diagnosis and Study of Transmissible Spongiform Encephalopathies

AIDS Res Hum Retroviruses 2004 May;20(5):507-12
HIV Type 2 Primary Isolates Induce a Lower Degree of Apoptosis "in Vitro" Compared with HIV Type 1 Primary Isolates.
Machuca A, Ding L, Taffs R, Lee S, Wood O, Hu J, Hewlett I