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Key words: PCR inhibitory substances, Mtb
The purpose of this OST project is to identify technical problems and limitations associated with DNA/RNA amplification systems and commercial in vitro diagnostic kits based on these systems. The long-term goal is to determine and document conditions under which DNA/RNA amplification systems and associated commercial diagnostic kits are ineffective and can produce false results. At present we are screening substances that can inhibit polymerase chain reaction (PCR) diagnostic tests and lead to false negative results. A PCR test system to detect Mtb was set up, optimized and is being utilized for the screening studies. A total of about 60 medicaments are being investigated and include drugs used in the treatment of tuberculosis, other frequently prescribed drugs, and several "over-the-counter" medications. Thus far, only one of these compounds appears to be a potent inhibitor of PCR and presently is under intense investigation. A system is being set up to determine whether or not metabolites of some of the compounds might be PCR inhibitors. Part of the research is being performed in collaboration with a DCLD/ODE staff member. Information gained from this project provides the Center with technical expertise and a knowledge base for evaluating the performance characteristics of novel molecular-based in vitro diagnostic devices. In addition, the expertise developed permits OST to continue being leaders in the development of national and international voluntary standards in the nucleic acid amplification technology area. [PreME, PostMS, ProA]
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Key words: PCR, international standards
Commercial DNA amplification-based medical device kit applications for the in vitro diagnosis of infectious and genetic diseases continue to be submitted to the Agency for premarket evaluation. In order to gain a comprehensive understanding of technology in this area, an OST scientist continues to lead the development of standards for the polymerase chain reaction (PCR) procedure with ASTM Committee E-48 on Biotechnology in collaboration with DIN (German Institute for Standardization) Committee E9 on Serodiagnosis of Infectious Diseases and Diseases of the Immune System. A clinical diagnostic laboratory general PCR standard and an HIV-specific PCR standard have been developed and published. The development of a PCR standard for the detection of Mycobacterium tuberculosis has been initiated. [Stds]
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Key words: DNA Diagnostic Technologies, Human Genome Project
As the human genome is being mapped and the thousands of individual genes are sequenced in the Human Genome Project, the potential commercial impact on DNA diagnostic technologies has become more apparent. CDRH has received premarket applications involving DNA technologies for diagnosis of infectious and genetic diseases. Although these applications utilize numerous new analytical approaches, even more sophisticated technologies are being developed. These include labeling with improved reporter chemical groups and new detector technology, DNA chips, automatic sequencing, and combinatorial hybridization. An OST scientist continued to serve as the Center focal point for keeping abreast of developments in DNA diagnostic technologies by monitoring published information, participating in meetings, and developing laboratory expertise in selected technical aspects of DNA diagnostics. He is an elected Voting Board Member on the "Tools for DNA Diagnostics Panel," Advanced Technology Program at NIST. In this role, he reviews and evaluates DNA diagnostics technologies being pursued by industry and that likely will result in novel products regulated by CDRH. [PreME, ProA]