TRENDS & PERSPECTIVES
Last December, the biotech giant Genentech (San Francisco) reignited the debate over regulation of laboratory-developed tests (LDT) when it filed a citizen petition with FDA. The petition asks FDA to regulate IVD tests used to guide therapeutic decisions and to pull from the market LDTs that make clinical claims without sound science behind them.
FDA is reviewing the 30-page document and “will respond directly to the petitioner,” says Mary Peper Long, a spokeswoman for FDA’s Center for Devices and Radiological Health. However, she did not indicate when the agency would respond.
Some analysts agree with Genentech that patient safety is at stake and that FDA needs to expand and strengthen its regulatory oversight of LDTs that physicians use to make highly specific treatment decisions. However, others believe that greater regulation of LDTs would be impractical, stifle innovation, and ultimately harm patient care just as personalized medicine is showing great promise.
While CMS regulates lab processes and protocols under the Clinical Laboratory Improvement Amendments (CLIA,) FDA issued a draft guidance in September 2006 saying it would use “enforcement discretion,” when it comes to regulating LDTs and its complex subset, in vitro diagnostic multivariate index assays (IVDMIA).
Last year, FDA exercised that discretion when it sent Laboratory Corporation of America (LabCorp; Burlington, NC) a letter stating the company was marketing its OvaSure Yale Test for early-stage ovarian cancer and a colon cancer test developed by another company in violation of the law. (LabCorp discontinued the ovarian test and stated it had developed its own colon test, but maintains FDA overstepped its reach in those cases.)
In its petition, Genentech argues that FDA has failed to apply clear and consistent standards and regulatory oversight to all LDTs. FDA’s arbitrary policy, Genentech says, means that physicians could be basing patient selection and making dosing decisions on unapproved pharmacogenetic test results that are false or misleading.
Genentech also says that FDA’s failure to apply consistent regulatory oversight to all LDTs creates inequities in the marketplace. Such inequities will deter innovation and impede the success of personalized medicine, Genentech says.
Manfred Scholz, PhD, president of Scholz Consulting Partners LLC (Medford, MA), agrees that patient safety is at stake. “The LDT designation is seen by many as a convenient loophole to avoid FDA oversight when developing new IVD tests,” he says. “This is a serious issue to any drug manufacturer and carries great risks for patients. Medical product sales, including LDTs for IVDs, without oversight invite quackery.”
Glen Freiberg, president of RCQ Consulting (San Diego,) says Genentech’s economic concerns are equally legitimate. Genentech is not only pioneering the development of targeted therapies, most notably the breast cancer therapy Herceptin, but is now also developing companion diagnostics that can identify appropriate patients for novel, targeted treatments. “They are bringing in-house the expertise to do the drug-diagnostic synergy,” Freiberg says. “Leaving the CLIA labs in place as is would be almost like having an immediate generic knockoff after they go through the FDA processes, and that would hurt them long-term.”
Freiberg believes that if done right, what Genentech is asking for would not put too onerous a burden on FDA. “Reclassifying tests such as the ones in the Genentech petition and downclassifying many of the more traditional tests could balance FDA’s workload to update the risk/review paradigm as is the case in the European Union’s IVD Directive,” he says.
However, the Coalition for 21st Century Medicine, which represents IVD companies, clinical laboratories, and researchers, says that if FDA had to approve all laboratory tests for use in drug or biologic therapeutic decision making as Genentech is requesting, it would delay the introduction of many critically needed diagnostic tests and prevent them from ever becoming available.
The coalition says Genentech’s petition ignores the rigorous, well-established regulatory system for LDTs that already exists, including not only CLIA but also various states and professional societies and physicians’ use of peer-reviewed literature in clinical decision making.
Jeffrey Gibbs, JD, a lawyer with Hyman, Phelps & McNamara (Washington, DC), believes FDA’s requiring more oversight of LDTs as Genentech asks would not be practical. “There are things that FDA has to leave alone because it only has limited resources,” he says. Regulating all LDTs “intended for use in drug or biologic therapeutic decision making as Genentech requests would swamp the agency.”
Also, he says, what Genentech is asking for in its petition will require FDA to go through the process of rulemaking, “which will be a very complicated and long-term task.”
