Manufacturing a medical device is one thing, but doing so without crossing swords with the multiple regulatory jurisdictions now in operation is no mean feat, either. Custom devices are suddenly of interest for two regulatory entities so far in 2019, but the FDA’s final guidance for combination product postmarket safety reporting is another consideration on which device makers dare not sleep.
Custom Devices Topical for IMDRF, Anvisa
There are certainly more complicated regulatory requirements than those pertaining to custom medical devices, but Brazil’s regulatory agency, the National Sanitary Surveillance Agency (Anvisa) and the International Medical Device Regulators Forum both posted draft guidances for custom devices recently, making compliance rather complicated for companies doing business in multiple markets. Anvisa and the IMDRF are only the latest entries in this space because the American FDA and its counterparts in the U.K., Australia and Canada have each already put their own stakes in this regulatory ground.
Anvisa announced the draft guidance for custom devices in September 2018, which according to a consultant’s analysis will require registration for custom-made, adaptable, and patient-matched devices. Makers of class III and IV custom devices will have to undergo inspections, but this requirement will not be extended to class I and II devices. There has been a backlog of Anvisa inspections of all types for several years, but the agency said the backlog will soon be a thing of the past.
The IMDRF draft guidelines, with a consultation period that closed July 24, deal with regulatory pathways for custom devices and offer definitions for custom devices and related terms. The document also provides language for additive manufacturing and devices customized at the point of care, but the IMDRF said a number of regulatory bodies “are noticing questionable use of custom-made device exemptions,” including a growing volume of custom devices that fall into higher risk classifications.
The IMDRF’s discussion of additive manufacturing is brief, but it promotes the concept of a medical device production system (MDPS) when that equipment is used outside of a traditional manufacturing site. The draft said that regulation of such a system might be determined by the type of device that system is intended to produce, although the manufacturer of the system would still be liable for validating the use of that MDPS for a given device. There is seemingly the prospect of split and/or overlapping regulatory liability as well, however, as suggested by a passage in which the IMDRF said that responsibility for the medical device’s safety and performance is “with the manufacturer of the MDPS, along with the other responsibilities placed on a manufacturer in the jurisdiction where the MDPS is used.”
Inspections a Concern for Combo Postmarket Surveillance
The FDA needed three years to convert a 2016 rule governing postmarket surveillance of combination products into a working final guidance, but there was some language in the 2018 draft that carried over to the final guidance despite industry opposition. Another issue for some, however, was whether the Office of Combination Products at the FDA would ensure that FDA field investigators are on the same page where the guidance’s key principals are concerned.
The Combination Products Coalition gave voice to a number of concerns, but the group’s regulatory attorney, Bradley Merrill Thompson of Epstein, Becker & Green, also requested that the FDA clarify a few questions regarding the reporting timelines for combination products. Thompson suggested at one point that the FDA provide additional clarity as to when certain of the draft’s provisions are directed toward cross-labeled combination products. Thompson said the FDA is should take steps to provide field investigators understand the implications of the final guidance’s most important provisions.
In contrast, the Advanced Medical Technology Association made note of reservations regarding a sponsor’s liability for reporting when the device component of a combination product has malfunctioned. AdvaMed’s Steve Silverman suggested that the draft had crossed the unduly burdensome line by requiring the sponsor of a drug- or biologic-led combination device to evaluate the possibility that a malfunctioning device component would malfunction when used with other drugs or biologics.
Silverman said one problem with this approach is that the use of a given device with different drug or biotech products means there are differences in storage conditions, just one example of the complications arising from responding to a malfunction. Silverman also said that the requirement as spelled out in the draft removes the device maker – which is fairly certain to be in a better position to handle such a task – from the task of determining the risk of device failure when paired with other therapeutic agents. Despite the feedback from Silverman, a former director of the Office of Compliance at the FDA’s device center, this provision appears in the final guidance as well.