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Dear Senator Kennedy:
The American Society for Microbiology (ASM) appreciates the opportunity to comment on S. 736, The Laboratory Test Improvement Act. The ASM is the largest educational, professional, and scientific society dedicated to the advancement of the microbiological sciences and their application for the common good. The Society represents approximately 43,000 microbiologists, including scientists and science administrators in government, industry, and academic institutions working in a variety of areas, including biomedical, environmental, and clinical microbiology.
The ASM strongly supports external oversight of laboratory developed diagnostic tests. That oversight is best achieved by enforcement of the provisions in the Clinical Laboratory Improvement Amendments of 1988 (CLIA). In particular, the subparts of the regulations that govern proficiency testing, quality systems, personnel standards, inspection requirements, and CLIA enforcement procedures have been very effective. The ASM concurs with the goals of CLIA oversight, especially those that promote sound laboratory practices and ensure patient safety.
CLIA clearly states that laboratory directors are responsible and are to be held accountable for maintaining the safety and effectiveness of testing for the patient populations their laboratories serve. The ASM shares the concerns of others over the use of laboratory developed diagnostic tests for which analytical and/or clinical validation is inadequate or incomplete. Such behavior is a clear violation of CLIA and should subject culprit laboratories to specified sanctions. ASM is concerned that passage of S. 736, however, will create a significant negative impact because of the laborious and expensive paperwork required by the proposed legislation. The net effect would be to stifle development of clinically useful, desperately needed, carefully validated diagnostic tests.
Many of the currently available laboratory developed diagnostic tests are low demand tests that have great clinical impact. They are tests that private sector companies are unwilling to produce because of the likelihood they would not be profitable. As a result, commercial reference laboratories and hospital-based clinical laboratories have found it necessary to develop such tests on their own. By doing so, they provide a much needed resource for high quality patient care. Examples of such tests in the clinical microbiology arena include a wide variety of nucleic acid amplification assays: many for diagnosis of serious infectious diseases (including those that may be related to bioterrorism), some that detect antimicrobial resistance of public health importance, and other quantitative assays that enable physicians to monitor the efficacy of antimicrobial therapy.
ASM is troubled by the requirement in the proposed legislation for submission to the Food and Drug Administration (FDA) of analytical and clinical validation documentation for laboratory developed tests, that is similar to the current requirements of the FDA’s Premarket Approval (PMA) or 510(k) clearance process. Meeting this requirement would far exceed the resources of most laboratories performing laboratory developed tests. Especially for those unfamiliar with the FDA regulatory process, it would entail allocating precious time, labor and costs beyond those available to impacted laboratories, and resources that could be more appropriately used for diagnostic testing to the betterment of patient care. Furthermore, FDA review of the submitted documentation would duplicate activities that already take place during CLIA-mandated laboratory inspections. In the realm of molecular diagnostics, the laboratory accrediting organizations deemed qualified by the Centers for Medicare & Medicaid Services (CMS) have already incorporated (or are in the process of incorporating) rigorous standards that focus on this new genre of tests. Future CLIA inspections should consider adding a review of the verification/validation data for laboratory developed tests to assure that the test consistently produces accurate results. The survey review should also consider making the Laboratory Director responsible for correcting any deficiencies identified. If necessary, ad hoc focused inspections of laboratories developing “home brew” tests could be scheduled in the mid-term if the next biannual CLIA inspection will not take place in the near future.
An immediate impact of the additional requirements codified by S. 736 would be discontinuance of the development of new tests while laboratories determine whether to make the infrastructural changes necessary to achieve compliance. Eventually, the cost of laboratory testing would escalate in order to compensate for the additional overhead expense of FDA submissions. Smaller laboratories with limited staff and resources would be at a distinct disadvantage. They would be much less able to afford the costs associated with laboratory developed tests.
Finally, the ASM is also deeply concerned that the personnel resources available at the FDA would not be adequate to handle the additional demands associated with S. 736 in a timely fashion. This would prolong the time between the development of much needed laboratory tests and use of their results for the betterment of patient care, a particularly important consideration for critical tests in infectious diseases, such as improved diagnostics for emerging pathogens and/or antimicrobial susceptibility patterns. Having the flexibility to readily respond to such changes via laboratory developed tests greatly assists physicians in the appropriate management of their patients.
Susan E. Sharp, Ph.D., Chair, Committee on Laboratory Practices
Joseph M. Campos, Ph.D. Secretary, American Society for Microbiology