FDA has published a draft guidance titled Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection or Detection and Differentiation of Human Papillomaviruses. It contains recommendations for studies to establish the analytical and clinical performance of in vitro diagnostic devices intended for detection or detection and differentiation of human papillomaviruses (HPV).
The guidance says that the devices are used in conjunction with cervical cytology to aid in screening for cervical cancer. They include devices that detect a group of HPV genotypes, particularly high-risk viruses, and devices that detect more than one genotype of HPV and further differentiate among them to indicate which HPV genotypes are present.
FDA says that the guidance provides detailed information on the types of studies that the agency recommends to support premarket approval for these devices. It is limited to studies intended to establish the devices’ performance characteristics and does not address HPV devices that are intended to be used independent of a cervical cytology result. It specifically addresses devices that qualitatively detect HPV nucleic acid from cervical specimens, although many of the recommendations are also applicable to devices that detect HPV proteins. The guidance may be accessed at www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm181509.htm.
—James G. Dickinson [Washington Wrap-Up, November]
There is no timeline yet for doing it, but FDA still intends to regulate laboratory-developed tests (LDTs) under FDA “enforcement discretion,” CDRH acting director of chemistry and toxicology devices Courtney Harper told the RAPS annual meeting audience in September. LDTs are presently marketed under the Clinical Laboratory Improvement Amendments (CLIA) without agency premarket approval.
LDTs “present risks to patients,” she said. Harper defined them as tests that have been fully developed in a single laboratory for use only in that laboratory, and that have no premarket review, no independent research basis, and no requirement for clinical validity.
“A company announces it is setting itself up as a lab to develop a new test as a biomarker,” she told RAPS, “and the next week we’ll see a news release that it is starting clinical tests for that soon. To us, that means that they actually don’t have enough information about the parameters of that test, if they’re still doing clinical studies on it.” That tells FDA, she said, that the labs still don’t understand the tests’ clinical performance and that the labs are marketing them for what is an investigational use without giving patients their right to informed consent.
“CLIA doesn’t require any type of clinical validity,” Harper said. “It doesn’t preclude the labs from doing that type of research. All it requires is that the test be analytically valid. It does not require that you actually have knowledge of the link between the test result and the clinical diagnosis.”
Due to the wide variability in lab quality, she added, “it’s very difficult for a doctor or a patient to predict what they’re getting when they order a lab-developed test.”
Harper noted that FDA is actively considering a 10-month-old Genentech petition that says the bifurcated FDA/CLIA practice of regulating by business model “doesn’t make any sense.” She said that until FDA’s policy on LDTs is changed, “we’re evaluating tests by risk. We really need to make some significant public health and policy decisions.” She promised that the decisions would be made transparently and with stakeholder input. The best way for stakeholders to participate now is to comment on the Genentech petition.
Harper also said that FDA regards tests that are distributed between different sites within a single corporation as not qualifying as LDTs, but as different laboratories; such tests require FDA premarket clearance or approval.
She warned that companies selling LDTs have more responsibility for the potential uses of their products than many realize. Although a company may have labeled a product for research use only, it may know through agreements or conversations with customers that the test is being used for clinical purposes. So “they have a responsibility under [21 CFR 801.4] to correctly label that product. That means the company would not be able to look the other way and say ‘that’s their problem.’ A disclaimer doesn’t protect the company as much as some people think that it does.”
—James G. Dickinson [Washington Wrap-Up, November]
While FDA’s new leadership touts the importance of exemplary science at the agency, a 47-page petition seeking the reconsideration of the agency’s August 4 final rule on mercury-containing dental amalgam trashes the science FDA used in it. The petition also alleges a selective literature search and says that the agency’s clear priority was to “defend at all costs the continued use of mercury in dentistry.”
The petition was filed on September 3 by Tulsa, OK, lawyer James M. Love for 17 others, including the Washington group Moms Against Mercury and celebrity osteopath and Internet natural products marketer Joseph Mercola. It seeks a formal ban on encapsulated mercury amalgam fillings or, alternatively, their reclassification into Class III instead of the final rule’s Class II.
The petition says a “defensible” amalgam risk assessment would require a detailed and quantitative analysis of the exposure to mercury vapor in the general population, but FDA’s analysis “only alludes to average or typical exposure levels, citing dated (predating 1993) reviews which they themselves only cite other yet older reviews.” Further, it says, FDA’s assessment omits measure of those maximally exposed to mercury vapors—patients with up to 25 mercury-filled teeth. FDA stops at 10, it says.
Further, the petition says, FDA’s risk assessment did not assess mercury vapor exposure from fillings in infants as young as 3, notwithstanding evidence that fillings are made in such teeth and notwithstanding EPA’s stipulation in 1998 that such exposures are especially pronounced. In sharp contrast to FDA, the petition says, Health Canada did consider all such extreme exposures when recommending against the use of mercury amalgams in 1995.
On the agency’s previously much-criticized literature search to support its position, the petition says the agency failed to utilize “a methodological ‘weight of evidence’ of the toxicological literature.”
The petition says that although FDA has the resources and expertise to properly assess amalgam’s risks, its “clear priority is to defend at all costs the continued use of mercury in dentistry—even at the expense of the public health. It is not surprising, therefore, that FDA declined to validly and defensibly compare its estimate of the average or typical mercury vapor exposure to the very reference exposure levels it represents to be safe for the general population.”
—James G. Dickinson [Washington Wrap-Up, November]
FDA has issued a Strategic Plan for Risk Communication, outlining the agency’s efforts to release more meaningful public health information. The plan lays out a framework for FDA to provide information about products to healthcare professionals, patients, and consumers. It also outlines how the agency oversees industry communications.
The agenda involves 70 specific actions for the FDA to take over the next five years, 14 of which the agency commits to accomplishing over the next year. Some of these immediate items relevant to medical devices include the following:
* Designing a series of surveys to assess the public’s understanding of, and satisfaction with, FDA communications about medical products.
* Producing a research agenda for public dissemination.
* Creating and maintaining a useful, easily accessible internal database of FDA and other relevant risk communication research.
* Posting pictures of FDA- regulated products affected by Class I or high-priority Class II recalls as part of recall notices/information.
* Developing detailed action plans at the agency and center levels for implementing and achieving the proposed action steps, including timelines, responsibilities, and resource needs.
According to the press release, the plan reflects FDA’s belief that risk communications must be adapted to the needs of different audiences and should be evaluated to ensure effectiveness.
