To the Editor:

As President of the American Clinical Laboratory Association (ACLA; Washington, DC), I am writing on behalf of ACLA members to applaud Nature Biotechnology for clearly delineating why regulation of in vitro diagnostics by the Food and Drug Administration (FDA; Rockville, Maryland, USA) would set back the promise of personalized medicine by years, if not decades. I won't repeat the points made in your March editorial1 other than to emphasize that the negative consequences of FDA regulation for patients are very real.

Clinical laboratory tests advance personalized medicine by distinguishing those individuals who are likely to benefit from a particular drug or dosage from those patients with the same diagnosis who probably will not. When developed in the laboratory—under federal oversight by the Centers for Medicare and Medicaid Services' Clinical Laboratory Improvement Amendments (CLIA)—these tests can be quickly modified to take advantage of important new important developments in this rapidly advancing field of medical science. FDA's before-marketing review of these laboratory-developed tests would have a chilling effect on this rapid, critically important innovation by subjecting it to another layer of regulation and driving away the investment needed to validate and incorporate test modifications.

The dangers of introducing delays and overlap through FDA regulation can best be understood in the context of what genetic testing and personalized medicine has already achieved. Many tests developed in the laboratory have provided healthcare breakthroughs, especially in infectious disease and cancer. AIDS has been transformed from a deadly disease to a manageable chronic disease in large part because of laboratory-developed tests for diagnosing and managing HIV. Because HIV mutates so rapidly, there are over 20 antiviral drugs for HIV treatment and over 50 more in development.

Laboratory-developed tests have been essential in rapidly incorporating new information to identify which drug to use for individualized therapy. They allow treatment to move from a 'one drug suits all' approach to a much more individualized strategy based upon the unique genetic nature of each individual and his or her disease. Tests developed in the lab have also been critical in the nation's public health defense by allowing the identification of severe acute respiratory syndrome (SARS), coronavirus, avian flu and West Nile virus. Although many more examples exist, these underscore why laboratory-developed tests and their ability to respond rapidly to new and often menacing health challenges should continue to be allowed within the congressionally established regulatory framework that already exists.

If all laboratory testing were subject to FDA regulation, rare and low-volume tests for genetic diseases—such as spinal muscular atrophy, Gaucher's disease, Tay-Sachs disease and Canavan's disease, among many others—could be removed from CLIA labs' menus and no longer be available to parents of children afflicted with these diseases. Because of the small populations that would be available for clinical trial testing, these well-established and medically important tests would not be able to meet FDA requirements, and—with limited markets—could disappear.

Furthermore, FDA preclearance or preapproval of laboratory-developed tests before they could be commercially offered would dangerously impede the ability of the nation's clinical reference laboratories to innovate quickly. This would have a profound negative impact on healthcare delivery and the practice of medicine and would close an important public health 'safety valve' now provided by laboratory-developed tests. For example, the current ability and flexibility of various laboratories (including those in academic institutions) to respond to emerging medical needs enables them to offer services that would never generate the financial and operational returns necessary to allow broad commercial introduction of an in vitro diagnostic test kit for such conditions. In many cases, no in vitro diagnostic device manufacturer will ever manufacture a kit for such tests. If all laboratories were required to clear their tests with FDA, then many tests simply would not be made available by laboratories, just as they are not offered at present by any kit manufacturer.

In addition, other tests with broader application also would find it difficult to make their way to market. As a Health and Human Services recent report2 on personalized medicine notes, “Venture capital will likely remain the primary source of financing for young innovators in this space [that is, personalized medicine] due to the extraordinary risk associated with investing in healthcare technologies.” The HHS report goes on to suggest that small changes in regulatory policies and reimbursement outlook can have a direct impact on the ability of emerging firms to attract the necessary investment. The emergence of significant new barriers to entry into this market, in the form of new FDA premarketing requirements and the accompanying costs, almost certainly would make it more difficult to attract the needed investment. As a result, the ability of these new companies to succeed would be impeded significantly.

To allow this twenty-first century healthcare revolution to continue, ACLA has proposed a regulatory model that builds on interagency coordination between the Centers for Medicare and Medicaid Services and FDA, provides a publicly transparent test registry, is consistent with principles of least burdensome regulation, fills all the identified regulatory 'gaps', avoids overlapping and potentially conflicting requirements and allows a participatory approach that draws on the expertise of industry stakeholders. It is our sincere hope that the new administration will lead the effort to accelerate personalized medicine with a commitment to regulatory balance and allow this remarkable science to progress without placing needless burdens on a now thoughtfully regulated industry.