Pathways Can Shorten Devicemakers’ Road to Approval

Devicemakers looking to speed their products through the development process can get help from three lesser-known FDA pathways, according to two experts.

Early feasibility studies (EFS), first-in-human studies (FIH) and the Expedited Access Pathway (EAP) program can substantially reduce the time spent in the clinical trial stage, said device consultants Caroline Rhim and Meaghan Bailey of NSF Health Sciences in an FDAnews-sponsored webinar in June.

Early feasibility studies are small clinical studies designed to gain early insights into an innovative technology during the development process before starting a larger clinical trial. First-in-human studies fall under the umbrella of EFS.

Early Feasibility

The EFS program allows for a circular approach where clinical data can be used to inform decisions regarding device and protocol changes as well as nonclinical testing, Rhim said. And in this case, more nonclinical testing may not always be necessary to go back to the clinical study, she said.

Rhim added that an EFS of a new device or a new intended use of an old marketed device includes use in a small number of subjects, generally fewer than 10. These studies may also be used to evaluate the device design concept and use an iterative process to facilitate both device and clinical protocol changes.

“The new approaches include the ability to make changes through, for example, five-day notices versus those requiring prior FDA approval, because the large majority of the changes will not affect how the results are interpreted, because they’re not dependent on statistical analysis of patient-level data,” said Rhim.

One of the major goals of this program, added Bailey, is to bring clinical trials to the United States first.

“It is not always appealing for a company to conduct early-stage clinical trials in the U.S. due to the stringency of IDE regulations as compared to regulations in some other non-U.S. countries,” she said. “So this has been a pretty successful and efficient program that allows a company to have early, often, and consistent interaction with the agency, which is particularly beneficial for novel devices requiring clinical data.”

These studies are given high priority within CDRH’s review divisions, and can be a tremendous time and resource saver, Bailey noted. They save a company from doing unnecessary studies upfront and will inform appropriate studies that may need to be done in the future.

Expedited Access

The Expedited Access Pathway, Rhim said, is available for technologies that address an unmet medical need, and/or a life-threatening or irreversibly debilitating disease. This is a voluntary program that provides a manufacturer with priority review, increased interactive review, senior management involvement, and a case manager from the FDA.

“The thinking behind this is to have an open dialogue with the agency and foster an interactive process that will lead to either clearance, approval, or granting of these needed devices more quickly,” Rhim said. “In this review paradigm, there may be more uncertainty that the agency is willing to accept, and you may be able to move some of the data requirements to the postmarket [stage].”

The final guidance for the EAP program was published in April of 2015. The 21st Century Cures Act signed last December, however, added a new “Breakthrough Devices” section to the Food, Drug and Cosmetic Act. While similar to the FDA’s current guidance for EAP, breakthrough devices have some differences. For example, 510(k) devices are now eligible for the EAP program, and the Data Development Plan is now an optional part of the EAP program, where previously, it was required for acceptance.

“Up until recently, only Class III—or essentially PMA- and de novo-eligible devices—were considered for EAP designation,” said Rhim. “Under the Cures Act, Class II devices have been added for consideration, which will expand the number and types of devices to be eligible for EAP designation.”

One caveat, she added, involves combination products. If your device component qualified for the EAP program, you should talk to the FDA early to see if the EAP pathway is feasible, because combination products have other unique considerations that may preclude them from having this expedited access review. With these changes, there are many moving pieces that you will need to consider, said Rhim.

“So if the EAP is something you might be interested in, keeping an open dialogue with FDA on this option will be critical given all of the changes with 21st Century Cures,” added Bailey.

Guidance Coming Soon

Since the agency will be issuing a revised draft EAP guidance by the end of this year, companies may want to wait a bit longer before leaping into this pathway, said Rhim.

“Since the guidance is currently being modified and not yet issued, there could be substantial changes,” said Bailey. “This is not to say you should not consider this pathway, but since the details of the program and its parameters are shifting, it can add uncertainty to a regulatory pathway.”

Depending on the specifics of your device and circumstances, however, it may be the case that the new guidance could increase the likelihood of being accepted into this program. So it could benefit you to wait for that guidance to be published, Bailey said.

“Establishing your regulatory strategy is a journey, but the foundational steps of determining your indications for use and researching the competitive market should never be skipped,” said Bailey. “In many cases, FDA may have premarket regulatory pathways that can help you get to market more quickly, but you have to keep up with changes to old programs as well as keep your eye out for the addition of new ones.

She added, “FDA is open to interactive dialogue. You just have to ask.”