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December 2012 Volume 9 Number 4

Necessary Oversight or Intrusion into the Practice of Medicine?

By Sean W. Develin, DevRose Systems Ltd, West Chester, PA


Laboratory-developed tests (“LDTs”) have been vital tools for physicians for more than 30 years.1 The ability of laboratories to develop and run custom diagnostic tests has contributed to the growth of personalized medicine.2 LDTs may be used for research only, for guiding patient treatment, or as “companion diagnostics” – tests that are used to determine the safe and effective use of corresponding therapeutic products. Because of the proliferation of LDTs, the Food and Drug Administration (“FDA”) has raised legitimate concerns regarding their safety and efficacy.3 LDTs are increasingly used outside of the institutions that developed them, creating a situation where the accuracy and validity of the tests may be assumed rather than demonstrated. Driven by these concerns, the FDA announced its intent to subject companion diagnostics to FDA clearance in its June 2010 Draft Guidance for Industry and FDA Staff on in Vitro Companion Diagnostic Devices.4

The central position of this guidance is that when the use of an In Vitro Diagnostics (“IVD”) “companion diagnostic device is essential for the safe and effective use of a therapeutic product, the IVD companion diagnostic device and therapeutic product should be approved or cleared contemporaneously by FDA for the use indicated in the therapeutic product labeling.”5 While its underlying motivation is good, the proposed Agency action is problematic for several reasons. Critics, including the American Medical Association (“AMA”), are wary that additional regulation could stifle innovation, provide barriers to patient access, and interfere with the practice of medicine – where the FDA has no jurisdiction. In October 2011, a coalition of physicians’ groups led by the AMA presented these concerns as comments to the draft guidance.6 More than a year after the AMA comments were submitted, the Agency has not taken any additional action or tipped its hand; however, with President Obama’s reelection, it is likely the Agency will attempt to move forward unless a better alternative is identified. This article looks at key points of the AMA’s position in contrast to the FDA and industry positions and considers existing alternatives to FDA regulation of LDTs.

Identifying the Proper Source of Oversight

The AMA-headed coalition response to the draft guidance is as much a tactful warning to the FDA as it is an opportunity to comment. While the coalition acknowledges the need for diagnostics to be evaluated by a “trusted authority,” the coalition makes it clear that the FDA may not be that body.7 It is the physicians who have the authority and responsibility for practicing medicine and who evaluate the tools appropriate for their patients. As such, the coalition cautions that “efforts to expand beyond the FDA’s existing regulatory scope will likely engender legal challenges.”8 Of specific concern are direct intrusions into the practice of medicine. Yet even if the FDA stays within its bounds, there is the potential that regulation will “restrict access to diagnostic tools that…physicians deem appropriate in the care of their patients.”9

There is also a strong argument that LDTs are already appropriately regulated. Beyond physician involvement in evaluating LDTs, the coalition argues that the majority of these tests that constitute companion diagnostics already fall under the Clinical Laboratory Improvement Act of 1988 (“CLIA”), which includes “continuous monitoring to ensure the analytic sensitivity, analytic specificity, accuracy, precision, reportable range, and reference interval of tests performed by the accredited laboratory.”10 In addition to CLIA requirements, “more than 90 percent of the laboratories performing LDTs undergo additional certification by the College of American Pathologists (“CAP”) to ensure clinical validity of tests….”11 Laboratories operating under CLIA/CAP are also subject to continuous monitoring that ensures continued analytic validity.12

Because of the scope and potential impacts of the draft guidance, the coalition also urges that the FDA pursue this course of action through the rule-making process rather than through guidance.13 Guidance offers the FDA its swiftest means to act but carries with it the untested assumption that the Agency has the authority to regulate the companion devices in the manner described. The rule-making process could better protect all parties by properly testing the Agency’s position and imparting the necessary legitimacy and authority to future enforcement actions. Without such authority, any attempt by FDA to enforce the guidance could result in an Agency rebuke on par with United States v Utah Medical Products, Inc.14 In that 2005 case, the United States District Court for the District of Utah, Central Division, denied the government’s petition for permanent injunction against a medical device manufacturer. The government argued that because the manufacturer did not conduct certain operations as specified in non-binding guidance, it was in violation 21 CFR 820, The Quality System Regulation. The court found for the manufacturer in a strongly worded opinion that was seen as black eye for the Agency.

An alternative approach to LDT regulation would be to enact a statute to deal with the issue. Bill H.R. 3207: Modernizing Laboratory Test Standards for Patients Act of 2011 was submitted to the House Committee on Energy and Commerce two days after the AMA filed its comments on the FDA Draft Guidance.15 The Bill would amend the Public Health Service Act to require the Secretary of Health and Human Services (“HHS”) to establish a single publicly accessible test registry data bank of laboratory-developed tests and direct-to-consumer DNA tests, which shall include information on the purpose of each test, the claimed use or uses of each test, and information regarding the analytical validity of each test.”16 Additionally, under H.R. 3207, authority to regulate LDTs would reside not with FDA, but with the Centers for Medicare & Medicaid Services (“CMS”), which oversees CLIA certifications.17

To date the Bill has not been referred to the House and GovTrack.us reports H.R. 3207 has a six percent chance of being enacted.18 But it is further evidence that while regulation of LDTs is needed, it could originate in something more than administrative agency guidance and the existing CLIA/CAP model may be the better “trusted source.”

The Impact on Innovation

Both opponents and advocates of the FDA’s position cite anticipated impacts on innovation in support of their arguments. Comments from Roche Diagnostics, the major IVD manufacturer, indicate that it is squarely on the side of FDA regulation, while critiquing the Agency’s position for not being aggressive enough.19 Roche argues that without uniform FDA regulation that includes LDTs, “IVD manufacturers will have little incentive to conduct the research, development and clinical validation of the novel tests that will drive personalized medicine.”20 The Roche argument is not without merit and will likely find sympathetic ears at the FDA. But is the path that Roche and the FDA advocate really the one that will “drive personalized medicine?” As with any regulation of science, there exists a need to balance the interests of safety and innovation.

The AMA position stands in direct contrast to the FDA position, emphasizing the role of “physician-driven scientific inquiry” and the role of laboratories themselves in “developing quality tests to serve the physician and patient population for more than 30 years.”21 The AMA warns that regulatory action requiring all companion diagnostics to be cleared by the FDA would risk “ignoring a large number of tests that may perform better than those [FDA] clears/approves” and “stifling the innovation that drives those tests.”22

Where to Go From Here?

Agency guidance may be the incorrect method for initiating FDA regulation of LDTs, but it has served to put the issue on the table and open up the debate. Following President Obama’s re-election, it is unlikely that the FDA will do an about-face, and with H.R. 3207 unlikely to advance, the next move belongs to the Agency. But if that move interferes with patient access to care or trespasses on the practice of medicine, the legal challenges the AMA has warned of may very well materialize.

1October 12, 2011 comments of the American Medical Association, American College of Medical Genetics, American Congress of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and College of American Pathologists re: Draft Guidance for Industry and FDA Staff on in Vitro Companion Diagnostic Devices, at 3.
2Id. Personalized medicine refers to the use of patient and human genetics to customize diagnosis and treatment for a particular patient.

Docket No. FDA-2011-D-0215, Draft Guidance for Industry and Food and Drug Administration Staff, Administration Staff, In Vitro Companion Diagnostic Devices, July 14, 2011, at 5. The FDA guidance may be accessed at http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm262292.htm


Id., at 4. LDTs are in vitro tests, conducted on biological materials isolated outside of the body.




October 12, 2011 comments of the American Medical Association, et al. See note 1 for a complete list of coalition members.


Id., at 1.




Id., at 2.

11Id. It should be noted that CAP is one of the parties joining AMA in its comments.



Id., at 1.

14United States v. Utah Med. Prods., 404 F. Supp. 2d 1315 (D. Utah 2005). The Quality System Regulation is the centerpiece of medical device regulations, laying out a comprehensive framework for their design, development and manufacture. In finding for the manufacturer, the court concluded that the requirements of the regulation were met even though they were accomplished by means that differed from guidance.

http://www.govtrack.us/congress/bills/112/hr3207 (last visited Dec. 12, 2012).






Id. This number, while small, has been trending upwards since President Obama’s re-election. GovTrack.us is also reporting the bill has a 21% chance of getting past committee.


October 11, 2011 comments of Roche Diagnostics re: Draft Guidance for Industry and FDA Staff on in Vitro Companion Diagnostic Devices.

20Id., at 2.
21October 12, 2011 comments of the American Medical Association, et al., at 3.

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