Regulatory Editor

FDA has heard more than plenty about its attitude toward clinical trial data from trials conducted outside the U.S., and the agency has responded with a draft guidance addressing such data sources. Device makers who hope for a fresh start on the question might be disappointed to see a passage stating that the draft "is not intended to announce a new policy, but to describe FDA's existing approach" to OUS clinical trial data used in support of an FDA device application.

The emergence of the draft guidance may strike some as interesting given that FDA published a draft rule on the subject of good clinical practices (GCPs) for OUS studies in the Feb. 25, 2013, Federal Register under the title, "Human Subject Protection; Acceptance of Data From Clinical Studies for Medical Devices." The listing of that draft rule at does not include anything suggestive of a final rule, but the draft rule emerged after passage of the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), which amended the statute where OUS clinical trial data are concerned. FDA points to FDASIA as a justification for issuance of this draft guidance.

The draft OUS acceptance guidance acknowledged the existence of the proposed GCP rule, which the draft guidance said would, "when finalized . . . require that foreign clinical studies of" devices "be conducted in accordance with good clinical practices." However, the document acknowledged that FDA's regulations currently address acceptance of OUS studies of PMA studies only, and not those in support of 510(k)s, de novo filings, and humanitarian device exemptions.

FDA also posted an information sheet in June 2014 on the OUS study matter, but this document applies to the centers handling biologics and pharmaceuticals as well as the Center for Devices and Radiological Health. The document said little specific to devices other than to note that any OUS trial data used to leverage an FDA application has to hew to the provisions of the Declaration of Helsinki and to the laws and regulations of the nation in which the study was conducted.

Section 1123 of FDASIA modifies sections 569A and B of the Federal Food, Drug and Cosmetic Act to require that FDA work with regulators in other nations to harmonize clinical trial regulations (569A) and to accept OUS data from other jurisdictions – specifically mentioning the European Union – so long as the sponsor can demonstrate "that such data are adequate under applicable standards to support approval, licensure, or clearance of the drug or device in the United States." The draft guidance makes note of this as well as the statute's requirement that FDA provide the sponsor with written justification for rejecting OUS trial data. However, FDASIA seems to offer little in the way of prescriptive language regarding the agency's approach to these issues.

The draft argued that FDA "has long accepted OUS clinical data in support of device submissions," even prior to passage of FDASIA, and points to a 2001 guidance on acceptance of "foreign clinical studies," again a document that is not device-specific. The draft recycles agency boilerplate on the subject of the criteria for valid scientific evidence, but said little else other than to recommend sponsors contact the agency prior to commencing with an OUS study or, in the case of a study already underway, contact FDA "at the earliest possible stage." A sizeable portion of the draft depicts seven scenarios in which a device maker brought OUS data to FDA in support of an FDA application and how those trial data were handled.

Amy Dow of Epstein Becker & Green (EBG; Chicago) e-mailed a set of remarks to Medical Device Daily, stating that the draft "demonstrates the agency's ongoing efforts to increase transparency of its expectations for clinical trial data in support of marketing authorizations." Dow said the draft "provides a useful roadmap for companies seeking to use existing clinical trial data from OUS studies," adding, "particularly useful are the hypothetical scenarios included in the draft guidance."

Dow said the scenarios describe "various types of OUS clinical data an applicant sought to use, the challenges associated with the use of that data, additional analysis or collection of additional data recommended by FDA, and the outcomes of the applicant's collaborative efforts with FDA." She added that these examples "remind applicants of the importance of early collaboration with FDA when seeking to use OUS clinical data, as well an increased willingness on the part of FDA to be flexible and work with applicants to utilize existing data." The end result, Dow stated, may be "a reduction in the number of studies that need to be repeated to meet FDA's requirements."

The examples do not suggest any dilution of FDA's expectations regarding the quality of those data, Dow said, but do suggest "the potential for greater flexibility in considering ways in which additional analysis or small confirmatory studies may be used to account for weaknesses in existing data." She added that the draft is "a positive for industry," but questioned whether FDA has the resources "to collaborate fully with applicants in the manner described in the draft guidance."

NC's Adams offers device tax repeal bill

The device tax repeal is not a dead letter if recent congressional activity is any indicator. The Senate Finance Committee has scheduled an April 23 hearing on the matter, but Rep. Alma Adams (D-North Carolina) has jumped into the fray with a bill that would repeal the tax and offset the lost revenues by closing loopholes for oil companies. The net effect is to pit big energy against the device industry in what is sure to become a lobbying scrum should H.R. 1533 gain any significant traction on Capitol Hill.

As matters currently stand, the Medical Device Tax Elimination Act enjoys the support of only four co-sponsors, all members of the Democratic Party, and the bill is on the docket for the House Ways and Means Committee. A companion bill in the Senate sponsored by Sen. Ed Markey (D-Massachusetts) would exert essentially the same effect, and will debut in the Senate Finance Committee. As is the case with H.R. 1533, the govtrack website gives S. 844 a 1% chance of passage. At present, Markey's bill lacks co-sponsors despite its introduction the day after Adams' bill, which was introduced March 23.

Medical Device Daily will report on the Senate Finance hearing in a subsequent issue. //

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