FDA Proposes Type V Master File for Combo Products

The FDA’s drug center has proposed the use of the type V drug master file (DMF) to report changes to the device portion of a drug-device combination product, a proposal that could prove more efficient than the current process. One of the considerations driving the draft guidance is that drug manufacturers often rely on a single device platform for delivery of multiple drug agents, and the use of the type V DMF would streamline the process of updating the agency on any changes to that device.

The draft guidance takes up matters such as administrative information and the protocol for advising the holder of the device premarket authorization of the intent to include that information in the DMF filing. The FDA stated that the use of this form is not compulsory, although the use of a single device platform for multiple drugs suggests that drug makers would be motivated to use the form. The scope is limited to combination products for which the FDA’s Center for Drug Evaluation and Research has primary jurisdiction, and the draft indicates that its terms may be appropriate for combinations in which the device consists at least in part of “electronics and/or software” that meet the definition of a device.

One of the keys to the use of the CDER draft will be in determining when the FDA’s device center has deemed a software function to have met the definition of a device. Under the 21st Century Cures Act, the statutory definition has been more clearly laid out, although the FDA is still reacting to that legislative mandate. As an example, the Center for Devices and Radiological Health recently posted its draft guidance for clinical decision support (CDS) software, which spells out some of the conditions under which a CDS would and would not be regulated. That draft is not yet in final form, however.

The type V master file is perhaps the least commonly used of the DMF submission types, and can be used to update the agency on a risk evaluation and mitigation strategy (REMS). However, a related REMS draft guidance issued in 2017 is still not available in final form, making the type V DMF a document with a substantial body of uncertainty behind it. The comment period for the type V DMF combination product draft closes Dec. 30.

No Easy Answers for EtO Dilemma

Despite the FDA’s preoccupation with digital regulation, the quandary over the use of ethylene oxide (EtO) has grabbed the rapt attention of device makers and the agency even though the problem has attracted no discernible attention from Capitol Hill. A recent FDA advisory hearing suggests that device makers won’t be able to readily shift to another sterilization method, although the Illinois state legislature nearly passed legislation that would have severely restricted the use of this sterilant in the Prairie State.

The 24-hour summary of the Nov. 6-7 advisory hearing stated that the FDA might consider allowing device makers to use less EtO when a less rigorous sterility assurance level might be appropriate. The difficulty with some of the available alternatives is that many of them exhibit a deleterious effect on many device materials, and the capacity for most of the alternatives is limited and cannot be expanded rapidly. Entirely novel approaches to terminal sterilization would require years to develop and implement, and the net effect is to suggest that there can be only marginally reduced reliance on EtO in the near term.

A report in the Chicago Tribune indicates that a committee in Illinois state Senate rejected a bill from the state House that would have banned hospital use of EtO by 2023, and would have required a sterilization facility to relocate to a less densely populated area. However, the sponsors of the legislation vowed to resurrect the bill next year. Sterigenics Inc., has already shuttered its high-volume operation in Willowbrook, Illinois, while two sites in Georgia have also been under pressure to suspend or cease EtO sterilization operations.

The Advanced Medical Technology Association has responded to the predicament with a number of press releases, but the group has also set up a section of its website for access to information about the EtO predicament. Among those is a webpage that depicts a number of sources of EtO that far exceed the EPA’s limits, a list that includes lawn mowers and charcoal grills.