A String of Pearls for Navigating the FDA

Masters of Industry: Digital Health - Threat or Opportunity?

WASHINGTON, DC – Having OIS@ASCRS 2018 here provided the perfect opportunity for representatives of the US Food and Drug Administration to impart wisdom on how attendees can help streamline application and approval processes for their innovations. The OIS@ASCRS Master Class, held the morning after OIS@ASCRS, featured staff members from the FDA’s Center for Devices and Radiological Health (CDRH), who focused on pathways for expediting ophthalmic device innovation. Here are some key takeaways from the session.

501(k) Premarket Notification

Denise Hampton, PhD, associate director of the Division of Ophthalmic and Ear, Nose, and Throat Devices (DOED), noted three situations that require 510(k) premarket notification: when a device is introduced into the market for the first time; when the indications change for a cleared device; or when significant changes are made to a cleared device. The total time to decision (TTD) for this process is already less than in some other specialties, she said, and recent changes to the Medical Device User Fee Amendments (MDUFA) will result in a further decrease in TTD through 2020.

She also pointed out a number of things that can cause delays in this process, such as not providing enough rationale for alternate test methods, or incomplete submissions. Among the best practices Dr. Hampton offered for avoiding delays are making sure the submission is clear and organized, including an explanation of why the 510(k) is being submitted, and only including information necessary for the submission.

Digital Health Functionality Initiatives

Ron Schuchard, PhD, medical physicist for the FDA’s Diagnostic and Surgical Devices Branch within the DOED, noted that medical mobile apps, artificial intelligence, and software diagnostics, among other innovations, are causing a paradigm shift. He noted current premarket time lines, which are suited for hardware-based products, will need to shift to keep up with the faster development of software as new challenges such as cybersecurity and non-physical products arise. The content in submissions may be significantly different than what has been previously seen. Risk assessment will be important; not only will the key functions of a device be assessed, but also its vulnerable aspects and protections against those vulnerabilities from impacting key functions.

‘Partner with Patients’

Michelle Tarver, MD, PhD, medical officer, DOED, said the CDRH wants to “partner with patients” as part of its strategy to focus on more patient-centered outcomes and preferences. To do so, CDRH is facilitating interactions with patients, and increasing the use and transparency of patient input as evidence in decision-making. The patient’s role has evolved from when the doctor made most healthcare decisions to where the patient should now be considered a partner. By understanding more about patient needs, experiences, and preferences, an improved “patient-centric” healthcare can be achieved.

Measuring patient reported outcomes (PROs) can capture information about symptoms (prevalence, impact, tolerability), functioning, satisfaction, expectations, health-related quality of life, compliance or adherence, and adverse events. Patient preference information (PPI) can be qualitative (identifying which outcomes or attributes patients value most and which factors affect patients’ perspective on risk and benefit) or quantitative (providing estimates of how much patients value different outcomes or attributes and trade-offs patients are willing to make). Dr. Tarver recommended that if a study uses either PRO or PPI, the study sponsor should contact the FDA early in the process.

Early Feasibility Study (EFS)

Angelo Green, PhD, acting branch chief of the Contact Lens and Retinal Devices Branch within the DOED, explained that an EFS is a small study (about 15 subjects) that involves the use of a device design that may be early in development, or a new indication for an existing device. The study must be designed to gain initial clinical insights or proof of concept when additional nonclinical testing cannot provide the information needed to advance device development. An EFS can evaluate any type of device, and may be used to study a novel device, support new indications for a marketed device, or study expanded access for a device used for things such as compassionate use or emergency use. The EFS guidance recommends and encourages early and frequent interaction between the FDA and the sponsors.

Humanitarian Device Exemption (HDE)

Tieuvi Nguyen, PhD, chief of the Intraocular and Corneal Implants Branch within DOED, noted an HDE application is a marketing application to the FDA, either through the CDRH or Center for Biologics Evaluation and Research (CBER) for a device classified as a Humanitarian Use Device (HUD). An HDE must have no comparable device available commercially in the US. A HUD is a medical device “intended to benefit patients in treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals per year in the US.” Approval of an HDE application also depends on safety factors and probable benefit. Examples of ophthalmology HDEs are Second Sight‘s Argus II retinal prosthesis system and the Intacs corneal inserts for keratoconus.

Breakthrough Devices Designation

For the Breakthrough Devices Designation, a device must provide a more effective treatment or diagnosis of a life-threatening or irreversibly debilitating disease. It must meet at least one of the following criteria:

  • Represent breakthrough technology.
  • No approved or cleared alternatives exist.
  • Offer significant advantages over existing approved/cleared alternatives.
  • Availability is in the best interest of patients (e.g., addresses an unmet medical need).


Benefits of Breakthrough Device designation include interactive and timely communication during development and review, senior management engagement, prioritized review, efficient and flexible clinical study design, enhanced opportunity for pre- and postmarket balance of data collection for premarket approval (PMA) devices, and the opportunity for reduced manufacturing information in a PMA.

Four Key Takeaways

The FDA is an agency with defined processes that sometimes require completing multiple steps (and forms). But none of it is insurmountable, and there are ways to make the process go more smoothly.

  1. Pay close attention to all details of a submission and understand what is needed.
  2. Provide everything asked for and nothing additional.
  3. Be in touch with the appropriate FDA representatives early enough in the process to be sure things start on the right foot and stay on track.
  4. If the FDA calls, take the call.


As CDRH director Malvina Eydelman, MD, said the previous day during the FDA Fireside Chat session at OIS@ASCRS, “If you get a call from the FDA, and somebody from my staff says they want to schedule a teleconference, it’s usually a good idea to say OK.”

For questions about this article, please contact Steve Lenier at Steve@stevelenier.com.