You just designed the greatest, cure-all class II medical device of all time! Terrific! Now what? Just go to the FDA website, follow the step-by-step procedures for submitting a “traditional” 510(k), submit, and cross your fingers, right? Not so fast! You have reached a critical point in terms of strategic development considerations. You could try and go it alone, or enlist the support of an experienced medical device consultant to help navigate the process. For example, you might benefit from help in confirming the device classification and/or your choice of regulatory pathway for FDA review (there are four types of 510(k)s after all). In many instances there are alternate routes to make these decisions. If the device classification is not clear, you can submit a 513(g) for an FDA determination. An excellent option for deciding which, and how best to utilize a regulatory pathway is formal communication with FDA, utilizing their Pre-Submission program (Pre-Sub). The Pre-Sub program is often overlooked, but can save sponsors valuable time and money in the long run. The program and consultation with FDA is free and is designed to support successful registration of your medical device.
What is the FDA Pre-Submission Program?
To explain simply, Pre-Sub is a formal mechanism for requesting feedback from FDA prior to submitting a medical device application. It is important to note that Pre-Sub is not required, and is voluntary. The objective is targeted feedback to the sponsor prior to a formal submission. The feedback may be requested in the form of a face-to-face meeting, teleconference, or written response. The Pre-Sub program, as we know it today, was announced in a Draft Guidance in July 2012, which was finalized in February 2014. Formerly known as the pre-IDE (Investigational Device Exemption) program, FDA has since expanded the program to include a multitude of medical device submissions:
- IDE – Investigational Device Exemption
- 510(k) – Also known as a PMN-Premarket Notification
- PMA-Premarket Approval
- HDE – Humanitarian Device Exemption
- De novo petitions – Classification option for novel low to moderate risk devices without first being required to submit a 510(k)
- CLIA-Clinical Laboratory Improvement Amendments-knowing whether a clinical study requires an IDE.
- Certain INDs (Investigational New Drug Applications) and BLAs (Biologic License Applications)
All of the above are collectively referred to as Q-Submissions (Q-Subs). Each is assigned a unique identification number starting with the letter “Q” and followed by six digits (the first two represent the year of receipt and are followed by four showing the order in which the request was received by FDA that year). The Q-numbers must be referenced in all subsequent, related FDA communications.
When Should I use the Pre-Sub Program?
The Pre-Sub program is useful for a wide variety of regulatory strategies, however in terms of medical devices, it is particularly useful for those that 1) do not have a clear regulatory pathway, 2) utilize a novel technology, or 3) have indications for use that qualify them as a “first of a kind” device. While not required, the net result of a Pre-Sub is targeted, written feedback from FDA. Adherence to such feedback is of great value in terms of quality and compliance and highly desirable for those devices that might require more information to ensure a submission that FDA will accept for filing. In short, early feedback from FDA tends to ensure better quality data for inclusion in the actual FDA submission. However, Pre-Subs should be conducted prior to compiling any device documents or studies and it is important to keep in mind the Pre-Sub lead times (75-90 days timeframe for meeting or teleconference, 21 days for urgent public health issues.)
When Should I Not Use the Pre-Sub Program?
As noted above, Pre-Subs are not a requirement and may not need to be employed in the case of simple, straightforward 510(k) submissions that a sponsor/applicant has previously executed. Most submissions involving well-understood products or modifications are not preceded by Pre-Subs. However, FDA review of a longstanding program for the purpose of continually improving quality, should always be a consideration. On the other hand, the Pre-Sub should not be used to answer simple questions that could be done with informal requests. Pre-Subs are not alternatives to FDA pre-marketing review, nor does a Pre-Sub guarantee approval or faster processing of your application. FDA offers many other online resources and encourages you to refer to them, prior to utilizing the Pre-Sub program. A few of the online resources that may be of assistance during your development stages:
- CDRH Device Advice Website
- CDRH Division of Small Manufacturers International and Consumer Association (DSMICA)
- CBER Manufacturer Assistance and Training Branch
Contents of a Pre-Sub Request
Once you have decided a Pre-Sub is a relevant strategy for your medical device, it is important that the contents are complete and comprehensive. The following is an example of the types of material that will be required for FDA to make the best use of your Pre-Sub request:
- Cover letter explaining your reason for feedback
- Preferred form of feedback (if you are requesting a face-to-face meeting or teleconference, please list 3 available dates/times for the proposed meeting)
- Table of Contents
- Thorough description of your medical device, along with proposed intended use
- Planned testing strategy
- Specific questions on which areas you are requesting input
The value of the written record with FDA resulting from the Pre-Sub cannot be understated. In fact, FDA advises that in order to officially document the non-written feedback, “applicants will be responsible for developing draft minutes for a Pre-Submission meeting or teleconference, and provide the draft minutes via email to FDA within 15 calendar days of the meeting.” If FDA finds any discrepancies, they will provide edits to the draft minutes to the applicant. The drafted minutes will become final minutes 15 calendar days after the applicant receives FDA’s edits.
How do I request a Pre-Sub?
Instructions for requesting a Pre-Sub are spread throughout the Guidance and vary depending on the type of information or assistance sought. The assistance of a medical device consultant is recommended. When properly executed, consultation with FDA at the early stage of your device development program can reduce the odds of a refusal to accept, and may ultimately result in reduced interaction with the FDA during application review. According to RAPS, “Early consultation with regulators can provide sponsors with a better understanding of data requirements and may help to reduce regulatory risk and improve approval timelines.”
In addition to the Pre-Sub program, another strategy often overlooked by sponsors is FDA’s 3rd party review program. In many cases, the 3rd party review may help to ensure successful FDA review. The purpose of the program is to improve the efficiency and timeliness of FDA’s 510(k) process (the process by which most medical devices receive marketing clearance in the United States). “Under the program, FDA has accredited third parties that are authorized to conduct the primary review of 510(k)’s for “select” eligible devices.”
Regardless of the scope or specific request, PDG is comprised of expert consultants who can assist you in determining your FDA medical device submission needs. It is optimal to contact us in advance of any Pre-Sub requests or FDA meetings. Experience has taught us that rigorous preparation and strategic regulatory planning coupled with FDA collaboration provides the best results in getting a medical device to market sooner, as well as keeping it on the market.
Jodi Hutchins is an Independent Regulatory and Quality Consultant with over 15 years of global medical device registration experience, to include FDA 510(k) submissions. She held her most recent position for 9 years, as QA/RA Director for a worldwide distributor of medical devices.
Charles Jaap is Vice-President of Operations and Business Development for PDG, a global pharmaceutical and medical device consultant with extensive experience in the strategic development of drug products and medical devices. Please feel free to contact us for more information.
The opinions and statements in this paper are solely those of Charles Jaap and Jodi Hutchins and do not necessarily reflect those of PDG.