September 25, 2006
The Food & Drug Administration requires approval of diagnostic test kits sold to clinical laboratories, hospitals, and doctors, regarding these kits as medical devices subject to the agency’s regulation. But the FDA has generally exercised discretion in its oversight of in-house developed (home-brew) lab tests.
The agency regulates analyte-specific reagents (ASRs)—the "active ingredients" of in-house developed lab tests—but has not extended the rules to labs that develop tests in-house using commercially available ASRs or lab-developed ASRs. ASRs typically are ranked at the lowest risk level (class I, exempt from premarket review and subject to general controls), and the FDA has set minimal rules on their sale, marketing, and labeling.
Raising the Bar
Now, the FDA is setting the bar higher for certain new types of home-brew tests that use DNA data and an algorithm to provide physicians with results tailored to a specific patient’s disease condition and therapy management.
In draft guidance issued September 8, the FDA says it will regulate such tests—which it calls In Vitro Diagnostic Multivariate Index Assays (IVDMIAs)—defined as: "test systems that employ data, derived in part from one or more in vitro assays, and an algorithm that usually, but not necessarily, runs on software to generate a result that diagnoses a disease or condition or is used in the cure, treatment, or prevention of disease."
Why the FDA Acted
"More and more of these kinds of medical tests are being made available each year," said Daniel Schultz, MD, director of FDA’s Center for Devices & Radiological Health in a statement. The agency regards IVDMIAs not as ASRs, but as test systems subject to its regulation, noting that use of the complete IVDMIA—the assay and the algorithm—is required to get a meaningful result.
What makes these tests different, Schultz said, is that the algorithms are usually proprietary, marking it hard for physicians to interpret the results and ensure they are valid. "It’s important for the FDA to look at the data on which these tests are developed," he noted. The agency also says closer scrutiny is warranted because these types of tests are used to diagnosis and treat cancer and contagious diseases where a wrongful result could be fatal.
Market Impact
The FDA’s new direction is very significant for the clinical lab industry, Alan Mertz, president of the American Clinical Laboratory Association, told NIR. Gene- and protein-based testing is a major industry growth sector with enormous potential for benefits to patients, especially in determining therapy, so ACLA is concerned that added requirements do not stifle innovation and speed in this cutting-edge sector of personalized medicine.
Some diagnostics companies have already warned that the added time and costs for premarket review could hamper their progress in tapping new technologies. Nor are the added costs likely to be recouped, unlike for drug development. FDA officials have said that IVDMIAs on the market will be evaluated case-by-case. While some may require more data submissions, others might pass muster with little trouble.
Warning on ASR Marketing Practices
In separate draft guidance, also issued September 8, the FDA warned against certain marketing practices that are "inconsistent with the ASR rules":
- Combining, or promoting for use, a single ASR with another product such as other ASRs, general purpose reagents, controls, lab equipment, software, etc.
- Promoting an ASR with specific analytical or clinical performance claims, instructions for use in a particular test, or instructions for validation of a specific test using the ASR.
The agency also reiterated in the draft guidance its position that clinical labs that developed ASRs are acting as manufacturers of medical devices and are subject to FDA jurisdiction. While most ASRs are class I and do not need premarket review, certain ASRs when used as a component in a blood banking test are class II devices requiring 501(k) clearance, while ASRs in tests to diagnose contagious diseases, such as HIV or TB, or other tests used to screen blood donors, are class III devices requiring premarket approval (PMA).
Under the ASR rules, labs and diagnostics manufacturers must meet minimal requirements:
- Labeling: Must include a statement disclosing that the lab developed the test and it has not been cleared or approved by the FDA.
- Sale: ASRs may only be sold to manufacturers of in vitro diagnostics, labs certified under CLIA for high-complexity testing, and organizations that use the tests for research or other non-diagnostic purposes.
- Controls: Must comply with CLIA quality control requirements for such tests.
At-Home DNA Tests: Let the Buyer Beware…
Meantime, some in Congress are putting the heat on federal agencies to be more proactive in oversight of genetic tests being marketed directly to consumers over the Internet. The Senate Select Committee on Aging held a hearing late last July to highlight the issue: "Marketing Scam or Medical Breakthrough?"
In a report presented at the hearing, the Government Accountability Office looked at particular tests that purport to offer health and diet advice based on analysis of a person’s DNA and concluded that they lack "scientific validity" and produce misleading results.
GAO investigators tested the accuracy of kits by Suracell (New Jersey), Genelex (Seattle), Sciona (Colorado), and Market America (North Carolina). All four companies advertised that the kits, which cost $100 to $400, analyze four to 19 genes to determine a consumer’s personalized diet and lifestyle needs. Using DNA samples from two test subjects—a nine-month old girl and a 48-year-old man—researchers created 14 fictitious consumer samples and returned them to the companies for analysis. GAO found:
- The personalized information returned from the companies, which predicted that the fictitious consumers were at risk for developing cancer, diabetes, high blood pressure, and heart disease "cannot be medically proven at this time."
- Advice and health predictions from the companies varied widely, even among samples from the same individual.
- Suracell and Market America used their results to market expensive dietary supplements.
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September 25, 2006 - Table of Contents
