Medical Device Daily Washington Editor

Some of FDA’s recent guidances have made it clear that the agency intends to play a larger role in its regulation of diagnostics, and a recent warning letter suggests that despite talks with the agency, a company can end up with a warning for an assay previously covered under the Clinical Laboratories Improvement Act (CLIA), which is typically regulated by the Centers for Medicare & Medicaid Services.

Among open issues that persist is the question of “home-brewed” diagnostics.

The Oct. 11 warning letter to Exact Sciences (Marlborough, Massachusetts) was brief, noting that data the agency obtained from CMS was regarding Exact’s PreGen Plus assay for colorectal cancer screening and that the assay was used by LabCorp (Burlington, North Carolina) in both its main facility and in its plant in Burlington, North Carolina.

The use of the assay outside of Exact’s plant evidently served as the red flag that sparked FDA’s interest.

The letter states that the CMS information indicates that the assay in question is “a test that was designed, developed, validated and marketed by Exact Sciences rather than a test that was designed and developed by LabCorp,” which puts the assay outside “the scope of laboratory developed tests over which the agency has traditionally applied enforcement discretion.”

Given the lack of PMA or 510(k) approval, the agency cited Exact for misbranding and adulteration.

Jeff Luber, president of Exact, told Medical Device Daily that the company’s understanding was that the test “fell under the home brew regulations, and we had discussions about 15 to 18 months ago and thought the issues were resolved.”

He also said that the company is not going to contest the home brew issue and will instead focus on “get[ting] it taken care of.”

“We have met with them and proposed a 510(k) strategy ... and are waiting to hear back from FDA on that,” Luber added.

The Oct. 12 warning letter to Olympic Medical (Seattle, Washington) demonstrated once again that attention to detail is key in staying out of hot water with FDA, even for devices designed to cool the human body.

The warning letter did not note the number of citations listed on the inspectional form 483 (the inspection took place in April), but discussed eight violations.

FDA stated that it found the firm’s response to several of the more serious violations adequate, but the agency informed Olympic that “a follow up inspection will be required to assure that the corrections made by your firm are adequate.”

The maker of equipment designed to therapeutically manipulate the temperatures of infants and newborns, the Cool Cap and the Bili-Bassinet, was cited for failure to establish procedures for verifying that device characteristics conformed to design requirements.

In the case of the Cool Cap, which is applied to the top of a baby’s skull to lower body temperature, FDA said that “a measurement of the thickness of the two material layers of two clinical and two commercial caps found that the thickness of the patient-side layer ... was thicker than specified.”

FDA did not list the difference in thickness.

FDA stated that the company’s May 23 response to this finding “appears adequate,” thanks to a copy of a revised standard operating procedure (SOP) that mandated a thickness check of the caps.

However, the agency was not happy with the response to a similar finding addressing the Bili-Bassinet, a device designed for use in phototherapy. According to FDA, the test procedure for the unit “does not specify if the mattress is in the horizontal position during the test, and testing was not done at various angles the mattress can be set at.”

Olympic’s response to this finding was to develop a new checklist for mattress positions and another to check for mattress temperatures under operating conditions. The warning letter did not previously mention the mattress temperatures, but FDA said that the revised SOP for the mattress temperatures “does not include a conclusion, and many values on the table are left blank.”

Trade secrets, or perceived secrets, can pop up in a warning letter, but Olympic managed to trim any such information from the letter.

In a heavily redacted portion of the warning letter, FDA cited the firm for failure to “identify the actions needed to correct and prevent the recurrence of non-conforming products and other quality problems” in connection with problems that were deleted. FDA said that while “the corrective and preventive actions directly related to the [redacted] are considered adequate,” the company’s response nonetheless “does not address how similar issues would be prevented or detected in the future.”

The warning letter also cited Olympic for lack of procedures for handling and evaluating complaints. According to FDA, company documents included complaints of Cool Cap system calibration alarms that went off during treatment, “and then shut down treatment, as designed.”

Another complaint involved a Cool Cap unit that “would not fill with water during set-up,” and a third complaint about a unit that required a replacement cooling unit that “resulted in a power cycling problem during testing,” which the customer was said to have reported as “a bad crimp on an electrical connector.” The customer apparently fixed this.

The company’s proposed fix for its complaint-handling system was deemed inadequate because “your procedure does not include any time frames.” FDA also said that “the adequacy of your efforts to address the noted violations by reviewing customer service calls ... cannot be determined” until a subsequent FDA inspection.

At press time, Olympic had not responded to a call for comment.