FDA Explains CMP Policy for Clinical Trials

The FDA announced recently its new policy for the assessment of civil monetary penalties for failure to appropriately register a human clinical study at the clinicaltrials.gov website, providing sponsors with a 30-day grace period before the imposition of CMPs. Sponsors are advised that the penalties can add up quickly, given that the penalty can come to $10,000 a day for each violation.

The FDA said it will hear complaints from other entities about unregistered clinical trials and incomplete registrations, but many of the violations will be detected during inspections under the Bioresearch Monitoring program. The agency will send those suspected of a violation a pre-notice letter describing the violation and requesting that the offending party correct the problem within 30 days of receipt of the letter, but much of the focus will be on high-risk trials and companies with poor compliance records where clinical trial registration is concerned. Another factor will be whether the agency has reason to believe that the sponsor’s conduct of the study is violative for other reasons.

Should the sponsor fail to react within 30 days, the FDA may begin assessing CMPs, but the rule is not yet in force pending the closing of the comment period and finalization of the draft. The FDA said it is taking comment through Nov. 20.

Gottlieb Responds to Questions Regarding Apple De Novos

FDA commissioner Scott Gottlieb took to the agency’s blog recently to discuss the granting of two de novo applications by tech colossus Apple Inc., an event that seemingly caught medical device makers and others by surprise. Gottlieb seemed intent on answering questions about the speed with which the FDA turned around the de novo applications in question, but he did not address what some see as the more important question, that of the simultaneous announcement of the de novos and Apple’s unveiling of the requisite hardware platform, the Apple Watch 4.

The FDA had granted the two de novo applications for the heart monitoring apps to be used with the latest version of the Apple Watch, but the speed with which the agency had reviewed the de novos – which was achieved in no more than 33 days in either case – was no more conspicuous to many than the simultaneous announcement of the granting of the de novos and Apple’s unveiling of the Watch 4. Gottlieb said in a Sept. 26 statement at the agency’s blog, FDA Voice, that the agency was compelled by a need to “encourage greater innovation in digital health.” In addition, Gottlieb said the agency must respond to the perception that regulations are creating drag on digital health, and thus the FDA “must be as nimble and innovative as the technologies we’re regulating.”

Gottlieb makes several other points in this context, but nowhere does he take up the question of timing. It’s not as though this is an entirely exceptional incident. The FDA does, after all, occasionally make announcements regarding a product to coincide with major medical society meetings, but those announcement are often aimed at a more select audience and typically affect an entire class of products. One exception was the safety advisory regarding the Abbott Absorb device for the coronary arteries in early 2017, which the agency placed on its website prior to the expiration of an embargo on a medical society announcement regarding the device.

Left unanswered by Gottlieb’s response is the question of whether the FDA intends to make a habit of cooperating with device makers regarding the timing product announcements. This is a particularly salient question for the smaller companies in this space, who might see in all this a conspicuous degree of bonhomie between a government agency and a company with a market cap in excess of $1 trillion.

Breathing Room but Hefty Fines: NIH’s Final Rule for Study Registration

The National Institutes of Health has finalized the rule for registration of drug and device trials at clinicaltrials.gov, one of the most commercially important documents the agency has published in decades. While the NIH did relent on a couple of points essential to industry, it appears that the requirements will be retroactive, thus exposing device makers to a fine of $10,000 per day per violation for any studies that are not up to date regardless of when those studies first appeared at the clinical studies website.

The NIH notice of proposed rulemaking (NPRM) came to light in 2014, and the docket for this proposal drew more than 900 comments, some of which was reflective of a considerable amount of consternation by those in the life science industries. Among the concerns expressed by industry early on was that the draft rule would have forced the disclosure of confidential information that could compromise a drug or device maker’s competitive position. However, industry was not the only target of the rule. By some accounts, most of the failures to register a study are accounted for by researchers working on studies not sponsored by industry. In any case, members of the NIH team said in an article in the New England Journal of Medicine that only about 10% of the studies registered at clinicaltrials.gov include results data from the registered study.

The retroactive nature of the mandate suggests the FDA will be on the look-out for violations of the final rule by drug and device makers. There does seem to be a split on the question of Section 522 post-market surveillance studies, however. The NIH flowchart regarding clinical trial compliance under the Food and Drug Administration Amendments Act of 2007 – the law that gave rise to the NIH rule – suggests that Section 522 studies are only required to register at the NIH site if those studies are of devices in pediatric populations

Nonetheless, any laggardly performance in these non-pediatric Section 522 studies might show up on the FDA radar screen if the agency starts hearing from the public, or from Capitol Hill, about clinical trial compliance generally.

Makers of combination drug-device products were none too happy to see that the NIH draft had stated that trials of combination products would be treated as pharmaceutical agents for the purposes of trial registration. The NIH heard from a number of entities that the final rule ought to reflect the designation applied to the product by the FDA’s Office of Combination Products, which itself has come under a barrage of criticism of late. The final NIH rule conceded the point

On the point of disclosure of trade information, the NIH opted to give sponsors of clinical studies of unapproved drugs and devices a year after the study’s primary completion date to register the results of the study, although sponsors can avail themselves of an additional two years if they certify that they intend to continue development of the product in question. Disclosure of dead-end studies would be required upon the sponsor’s notification of abandonment of the study.

As for timelines, the NIH said the final rule goes into effect on Jan. 18, 2017, and that compliance will turn into enforcement three months later, on April 18, 2017. That leaves sponsors less than six months to determine which of their studies are subject to the final rule and get those studies’ data updated. After all, $10,000 per violation per day can add up quickly.

FDA New Draft Guidance: Medical Device Clinical Data from Trials Outside the U.S

Courtney A. Stevens, Esq. | Senior Attorney, Medmarc Loss Control

Last week, the FDA released draft guidance for medical device developers on utilizing clinical data obtained from trials conducted outside the United States. Many view this Guidance as a follow-up on a proposed rule the Agency issued in 2013 (Human Subject Protection; Acceptance of Data from Clinical Studies for Medical Devices), which would require that foreign trials comply with U.S. good clinical practices regulations if in support of a device application. In furthering this effort toward uniformity and consistency among trials internationally, this most recent guidance clarifies the participant protections that need be in place in order for the data to be deemed reliable by the Agency for purposes of application review. Continue reading “FDA New Draft Guidance: Medical Device Clinical Data from Trials Outside the U.S”