TRENDS & PERSPECTIVES

A comprehensive proposal for modernizing the regulation of IVD tests was outlined by AdvaMed (Washington, DC). During a meeting of the Department of Health and Human Services’ Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) in February. According to AdvaMed officials, the proposal would assure patient safety and timely patient access to all safe and effective diagnostic tests.

“We think the modernization of IVD regulations is an important way to ensure the future of diagnostics and to realize the promise of personalized medicine,” says Khatereh Calleja, JD, AdvaMed’s associate vice president, technology and regulatory affairs. “If you look at the growing interest in personalized medicine, we think this proposal fits in very well with our own increasing interest in moving toward personalized medicine since diagnostics plays a key role in this paradigm.”

To meet the challenges of providing timely patient access to safe and effective diagnostics, AdvaMed is advocating the adoption of a flexible, risk-based regulatory approach that would do the following: realign the intensity of regulatory oversight with patient risk/benefit; focus limited FDA resources on novel technologies with the highest risks; and apply a least-burdensome approach to all tests, whether made by IVD manufacturers or clinical laboratories.

AdvaMed’s risk-based regulatory approach is based on the following principles: FDA oversight of tests should focus primarily on the risk of harm associated with how the test result is used to treat patients; patient access to specialized test categories (i.e., rare diseases, rare usage) should not be harmed; and the new oversight system should be implemented through notice-and-comment rule making and guidance as appropriate.

In addition, in a letter to SACGHS, AdvaMed stated that its proposed risk-based approach focuses on the following factors for determining risk: risk associated with the clinical use of the test; degree of novelty of the analyte; degree of novelty of the technology; and the level of professional training of the operator.

“I believe AdvaMed will have a very difficult time with this objective and their criteria alone will create problems because the criteria ignore automation,” say Glen P. Freiberg, president, RCQ Consulting (San Diego). “If all four categories alone or in combination appear to create a risky test and the vendor creates an automated way to produce a reliable answer, what does this mean for the clearance or approval process? This is the same approach that was proposed with the initial CLIA 1988 regulations. That is to base part of the risk formula on the analyte.”

In announcing its proposed regulatory approach, AdvaMed also stated that it believes all clinical laboratories should be subject to the requirements and quality standards under the Clinical Laboratory Improvements Amendments (CLIA). AdvaMed added that FDA should oversee the safety and effectiveness of all diagnostic tests no matter where they are made because they have the same risk/benefit profile for patients. Industry analysts believe that implementing such proposals could be problematic.

“Clearly, the traditional IVD industry has had an axe to grind with clinical labs and FDA over the leeway given to labs in not being actively regulated by FDA,” says Thomas M. Tsakeris, president, Devices and Diagnostics Consulting Group (Rockville, MD). “However, this has changed with the advent of the IVDMIA initiative, and the question of compliance with FDA’s quality system regulation (QSR) for IVDMIA producers appears still to be problematic since IVDMIA labs would now be subject to both CLIA and QSR requirements.

“Thus, the burden of potential overregulation may now be felt by the labs as compared with traditional IVD companies. AdvaMed now proposes that all IVDs be regulated, including those developed and conducted by labs, and not just IVDMIAs. While this may be understandable from the traditional IVD industry perspective, this could spell disaster for the labs,” says Tsakeris.

“There is nothing in the Federal Food, Drug, and Cosmetic Act or CLIA suggesting that FDA has authority over laboratories, or should regulate them,” says Jeffrey N. Gibbs, JD, director, Hyman, Phelps & McNamara (Washington, DC). “The agency is already struggling to complete timely reviews of marketing applications and pre-IDEs for IVD manufacturers. Having FDA embark on the regulation of laboratories would tax FDA’s resources further, have a negative effect on a major source of innovation, and reduce availability of innovative tests, particularly for less-common diseases and conditions. Instead, the agency should be strongly encouraged to develop clear, predictable, transparent regulatory requirements for new tests, which would benefit the entire IVD industry and public health.”

Additional information about AdvaMed’s proposal can be accessed via its Web site at www.advamed.org.