Posted 19 August 2014
By Alexander Gaffney, RAC
A new final guidance document issued by the US Food and Drug Administration (FDA) is intended to "promote" clinical studies of new medical devices under the agency's Investigational Device Exemption (IDE) regulations, but no longer includes a program proposed by FDA in 2013 meant to accelerate the clinical assessment process.
Much like their pharmaceutical counterparts, medical device companies must first obtain approval from FDA to conduct a clinical trial on an investigational product. For devices, this approval comes from the submission of (and FDA approval of) an IDE application.
An IDE is essentially a targeted exemption from federal law. Under the Federal Food, Drug and Cosmetic Act, no medical product may be put into interstate commerce without first having obtained approval from FDA. When regulators grant a sponsor's application for an IDE, they are in effect giving them a temporary reprieve from those conditions so long as they conduct the trial according to federal standards.
But while most IDE applications are given full approval, since 2012 FDA has also been allowed to issue new types of "conditional" responses to IDE applicants with "outstanding issues" that would have otherwise been rejected prior to 2012.
Those "conditional" approvals are the focus of a new final guidance document, Decisions for Investigational Device Exemption Clinical Investigations.
As FDA explains in the guidance, the intent of the conditional approval process is to create a more timely and efficient process for starting IDEs for certain devices, "even when outstanding issues remain regarding the IDE submission."
The new process was created under the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), Section 520(g)(1) of which required that FDA not disapprove an IDE if any of the three following conditions are met:
- the investigation may not support a substantial equivalence or de novo classification determination or approval of the device;
- the investigation may not meet a requirement, including a data requirement, relating to the approval or clearance of a device; or
- an additional or different investigation may be necessary to support clearance or approval of the device.
In other words, many of the conditions set under FDASIA are intended to allow FDA to approve trials that might be imperfect in their scope, but not inherently flawed.
As Regulatory Focusreported last year, the guidance explained that conditional approval of an IDE may be subdivided into two different types:
- approval with conditions
- staged approval
Each of these approvals carries with it a unique set of requirements. For example, if FDA approves an IDE with conditions, the sponsor may immediately begin to enroll patients into a trial, but has 45 days in which to submit a letter to FDA addressing the issues raised by the agency. This type of approval is meant to reflect FDA's opinion that an IDE has sufficient information to allow human evaluation despite the minor deficiencies or late-stage problems with the trial design. FDA then has 30 days to respond to the sponsor, at which time it may choose to issue another approval with conditions if there are remaining issues, or issue a clinical hold on the study.
Staged approvals, meanwhile, reflect more serious concerns by FDA, and are meant to hedge risk on an incremental basis. Under this approval, FDA grants approval to a subset of the planned subject cohort, but withholds full approval until outstanding issues are corrected. Once again, sponsors have 45 days in which to respond to FDA.
New, Separate Letters
Another key portion of the guidance is aimed at communicating potential issues. While FDA won't necessarily be able to reject an IDE application under FDASIA, companies will almost certainly want to be aware of any issues that could preclude eventual approval of a device.
As such, FDA's guidance calls for sponsors to engage with it to communicate "outstanding issues related to the IDE through study design considerations and future considerations."
In FDA's June 2013 draft guidance, the agency outlined three types of planned communications: Study design assessments, study design considerations and future considerations.
While FDA's final guidance is largely consistent with the draft, it does make a few minor changes in this section. For example, FDA now says its "Future Considerations" letters, which are intended to outline things FDA believes should be done prior to a future marketing application, will now be communicated to sponsors as a separate letter. FDA has previously proposed packaging its contents within the decision letter.
FDA also indicated that it will communicate study design considerations separate from its decision letters, citing the potential for sponsors to become confused.
Proposed Program Dropped
One major difference between the draft guidance and the final guidance relates to a program proposed by FDA known as the Pre-Decisional IDE process. The voluntary program would have helped sponsors to design "high quality clinical trials" capable of supporting eventual marketing applications. FDA said it hoped the feedback would allow sponsors to quickly resolve issues and get their products approved more easily.
However, FDA announced that it will be shelving the program for the foreseeable future after some members of industry expressed concern that the process might be too time-consuming or resource intensive on FDA.
"Based on the comments received and FDA's consideration of the points raised, FDA will not pursue the Pre-Decisional IDE at the present time," FDA wrote.
Decisions for Investigational Device Exemption Clinical Investigations (FR)