US regulators today released a new draft guidance document that looks to clarify the US Food and Drug Administration's (FDA) expectations when it comes to approving an investigational device exemption (IDE) application that permits a sponsor to conduct a clinical study involving a medical device.
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 entails having sufficient preclinical data to support an IDE.
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 to certain standards.
But FDA has two other options available to it beyond regular IDE approvals: Conditional approval and disapprovals.
FDA's new draft guidance, Decisions for Investigational Device Exemption Clinical Investigations, released on 13 June 2013, pertains to conditional approvals granted under 21 CFR 812. In particular, FDA said it is interested in creating a more efficient and timely process for approving conditional IDEs - one that permits patients to be enrolled in a trial as soon as possible while simultaneously protecting their safety.
While the guidance doesn't apply to most IDEs, which have few if any substantial issues to surmount, it does affect a subset of IDEs involving "outstanding issues," offering them several mechanisms by which they can be approved.
FDA goes on to note that the guidance is the result of the FDA Safety and Innovation Act (FDASIA), which applied three new conditions with respect to IDEs: FDA may not disapprove an IDE because it may not support a substantial equivalence or de novo classification for the device, doesn't meet a data requirement, or doesn't fully support approval.
The 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 planning subject cohort, withholding full approval until outstanding issues are corrected. Once again, sponsors have 45 days in which to respond to FDA.
Feedback to Sponsors
And while FDA can't outright deny an IDE that doesn't support an approval decision, that isn't to say that a sponsor doesn't want to know this information regardless, FDA observed. To support a more efficient process, sponsors may also engage FDA in what the agency called "communication of outstanding issues related to the IDE through study design considerations and future considerations."
FDA also outlined three types of information conveyed in its communications: Study design assessments, study design considerations, and future considerations. Agency officials wrote that communicating deficiencies inherent in an IND will permit sponsors to voluntarily modify their studies to permit future approval. Those deficiencies, it wrote, will generally pertain to either the design of the trial (and in particular whether the endpoints are appropriate), various considerations of the trial (e.g. randomization, enrollment criteria and blinding), and future considerations (e.g. the limitations of certain data in regards to supporting specific claims or indications).
Pre-Decisional IDE Process
To meet the interest of sponsors for mid-cycle IDE review feedback, FDA said it is proposing the creation of a "new and voluntary" program that would "facilitate the development of trial designs that may support a marketing approval or clearance."
Regulators said they did not anticipate that the program will become a "routine step prior to submission of an IDE" or otherwise replace or substitute the existing pre-submission process, mostly because it would not be appropriate for the majority of sponsors.
The program, known as the pre-decisional IDE process, is a collaborative one in which regulators will collaborate with sponsors to design "high quality clinical trials that may support marketing applications if the studies are successfully executed and meet the stated endpoints without raising unforeseen safety concerns," FDA explained.
The process, FDA continued, will "enable sponsors to obtain timely feedback from review staff on a near-final IDE application, with the opportunity for a mid-cycle interaction with the review team to promote a clearer understanding and quicker resolution of major issues with device or subject safety as well as study design."
The guidance notes that as opposed to the usual pre-submission process, applications considered under the pre-decisional IDE program will require a more complete and thorough feedback process from reviewers by including data, full study protocols and reports. This, it added, should hopefully permit faster IDE submissions by helping sponsors to confront potential issues early on in the development process.
The meeting will occur 15 days after the submission of a pre-decisional IDE - itself a filing distinct from a normal IDE - and will last an estimated 90 minutes.
"Following the meeting, the sponsor has the option to request that the Pre-Decisional IDE be converted to an actual IDE, in which case FDA would issue a decision letter including the deficiencies and recommendations provided in the initial feedback," the guidance notes.
The guidance may be found here, and is open to comment for 90 days.
Decisions for Investigational Device Exemption Clinical Investigations