Ocular Therapeutix drew a US Food and Drug Administration (FDA) warning letter for failing to comply with post-approval study requirements (PAS) set as part of its ReSure Sealant’s conditional approval.
The warning letter, dated October 2018, cites the company’s failure to collect any data for its FDA-approved protocol—identified as a Device Exposure Registry (DER) study—as part of the PAS requirements in the 4.5 years since the conditional approval. Ocular Therapeutix’s ReSure Sealant was approved through the agency’s premarket approval application (PMA) pathway in 2014. In a 2015 earnings report, the company touted
the device as “the first and only sealant that is FDA-approved for ophthalmic use.”
The company and FDA engaged in discussions around how to proceed with the PAS requirements in 2017 and 2018. But in the company’s August 2018 response to multiple FDA deficiency letters, it indicated to the agency that “the PAS is no longer relevant because feasibility is not probable.”
Dan Bollag, senior vice president of regulatory affairs and quality at Ocular Therapeutix, told Focus
that the company has met with the agency after receiving the warning letter last October, though it was posted on FDA's website on Tuesday. Ocular Therapeutix "is pursuing an alternative registry approach to satisfy the post-approval requirement," Bollag said. "Prior efforts to satisfy the requirement included a post approval study of endophthalmitis rate, which has not enrolled patients," he added. "Following protocol approval, zero of 150 sites expressed interest in participating." Bollag also said that "zero reports of endophthalmitis in clinical and commercial experience with ReSure Sealant" have been filed to date.
The agency has the authority under the FD&C Act
to impose PAS requirements as a condition of approval when information on the long-term safety, effectiveness or reliability of a medical device is considered necessary to provide or continue to provide reasonable assurances.
Similarly, however, FDA’s Center for Devices and Radiological Health (CDRH) sent
warning letters last March to all three manufacturers marketing duodenoscopes in the US over inadequate progress with 522 postmarket surveillance studies
or lack thereof. The emerging surveillance and enforcement trend come as CDRH recently indicated
that PAS requirements are an area of increased scrutiny. The efforts also coincide with CDRH’s push
to strike the right balance between pre- and post-market data collection, particularly with the National Evaluation System for health Technology.
“A firm that fails to comply with such a post-approval study requirement violates section 519” of the FD&C Act,
Raquel Peat, director of the Division of Premarket Labeling Compliance at CDRH’s Office of Compliance, wrote in the Ocular warning letter. “In addition, a firm that repeatedly or deliberately fails to make reports under 21 CFR 814.84(a) may be subject to PMA withdrawal.” These reports are part of PAS requirements and must identify each device identifier in use for the device, among other data elements.
Under the condition of approval order, Ocular Therapeutix committed to evaluating incidences of endophthalmitis for cataract surgery patients treated with the ReSure Sealant device when used by a group of physicians as part of the DER study protocol that received FDA approval in 2016 and of the major ocular adverse events in the postmarket setting under a clinical post-approval study.
But the three interim reports submitted in 2017 and 2018 “reflected no progress in both site and subject enrollments” despite the fact that “FDA on several occasions provided…advice regarding enrollment strategies…and recommended alternative approaches as possible solutions to the enrollment issues related” to the company’s study, Peat noted. This contributed to the issuance of an overdue deficiency letter in March 2018 after the company did not respond to emails FDA sent to follow up on the provided recommendations and the company’s actions. In its May 2018 response, the company indicated to the agency that it had not received the original FDA deficiency letter due to a change in its point of contact.