FDA Pre-Subs: Best Practices, FAQs, and Examples

Best Practices 🔗

• Timing
  • Don’t do a Pre-Sub if your intended use and device description aren’t set
  • Otherwise, do a Pre-Sub as soon as high-risk regulatory questions are identified
• Question selection
  • Focus on questions that eliminate regulatory or clinical risk
  • Write specific questions that lead FDA to the answer you want
  • Write questions that give the FDA an opportunity to disagree
  • Avoid questions that FDA won’t be able to answer in a Pre-Sub or can be answered using Guidance
• Pre-Sub Preparation
  • Provide detailed background information for FDA to give accurate answers
  • Don’t provide extraneous background information
  • When providing background information, not only explain what approach you are using, but also explain why you are not using alternate approaches
  • Use FDA terminology
  • Quote FDA guidance back at the FDA
• The Call
  • Plan out expected FDA questions and responses
  • Keep in mind that FDA Pre-Subs can be somewhat of a negotiation with FDA; there is some give and take
  • Plan who will speak about which questions (we generally suggest having an regulatory consultant run the meeting)
  • Don’t waste time during the meeting on unimportant topics

Basic 🔗

What is a Pre-Sub? 🔗

A Pre-Sub is a mechanism for requesting formal written feedback from the FDA, and (optionally) a one-hour meeting.

A Pre-Sub is appropriate when FDA’s feedback on specific questions would help guide product development, performance testing, predicate selection, or other aspects of a 510(k), De Novo, PMA, or IDE submission.

Does a Pre-Sub cost money? 🔗

There is no FDA fee, however, preparing a Pre-Sub package takes significant effort. There is also a 60 - 75 day delay from when you submit your Pre-Sub and when you receive feedback. Time is money, as they say.

How many Pre-Subs are you allowed to do? 🔗

You can do as many as you like.

Do you have to do a Pre-Sub? 🔗

No. They are always optional.

How do Pre-Sub’s relate to 510(k)s? 🔗

Here is a diagram showing how pre-subs relate to a typical pre-market submission:

What is the process for doing a Pre-Sub? 🔗

The typical process looks like this:

1. Prepare the Pre-Sub
   1. Identify key questions
   2. Write intended use and device description
   3. Write any other documentation necessary for FDA to answer questions
2. Submit the Pre-Sub to FDA (Day 0)
3. FDA provides written feedback (Day 70)
4. Meeting (Day 75)
5. Respond with formal minutes (By Day 90)

If no meeting is requested, then steps 4 and 5 are skipped.

The day of the meeting is mutually agreed upon with FDA, and is typically between 70 and 75 days from submitting the Pre-Sub.

Although the actual timelines for the Pre-Subs can vary and have increased and decreased over time, as of April 2024, we’re seeing that FDA is typically hitting their 60 - 75 Day goals.

Where do Pre-Sub meetings occur? 🔗

We often do them over video calls, however, FDA has started allowing in-person meetings again post COVID.

What content goes into a Pre-Sub? 🔗

Here is a summarized list of content that’s included in a Pre-Sub. Note a lot of this is quoted and slightly modified from the FDA guidance:

• Purpose. The overall purpose of the Pre-Sub including goals for the outcome of the interaction with FDA.
• Agenda. A draft agenda proposing the topics to be presented and the estimated time for each agenda item.
• Preferred Meeting Dates. Three (3) or more preferred dates and times when you are available to meet.
• Attendees. The planned attendees, including each attendee’s position, or title, and affiliation.
• FDA Experts. Any appropriate FDA staff that are requested to attend the meeting if specific expertise may be needed.
• Device Description. Listing of any relevant previous communications with FDA about the subject device An explanation of how the device functions, the basic scientific concepts that form the basis for the device, and the significant physical and performance characteristics of the device.
• Proposed Indications for Use or Intended Use. This should include a description of the disease(s) or condition(s) the device will diagnose, treat, prevent, cure or mitigate, and a description of the patient population for which the device is intended.
• Regulatory History. Listing of any relevant previous communications with FDA about the subject device.
• Planned Follow-On Submission. FDA recommends that you clearly indicate what type of future submission (IDE, IND, CW, Accessory Classification Request, or marketing submission) is the focus of your Pre-Sub questions to help direct FDA’s feedback.
• Background Information. FDA recommends that you include sufficient background information and supporting documents to allow them develop feedback for the Pre-Sub questions you pose. This information might include:
  • literature articles
  • full device description with engineering drawings
  • proposed labeling
  • videos
  • red-lined protocol revisions
  • how you addressed, or plan to address, relevant guidance documents, regulations, special controls, or other applicable sources for your device or submission type.
• Specific Questions. A Pre-Sub should include clear, specific questions to allow FDA and the submitter to focus their efforts on issues most relevant to moving a project forward. You may wish to describe your perspective on the questions you provide FDA to inform FDA’s review.

How do you prepare a Pre-Sub? 🔗

We suggest using the PreSTAR dynamic PDF to compile a Pre-Sub. You can download the PreSTAR template here. Once you download it, you can select the options for a Pre-Sub and then fill in the various sections.

Once you have filled in this information, you can see the details

When is a good time to do a Pre-Sub? 🔗

It is generally too early to do a Pre-Sub if you don’t have a somewhat settled indications for use and device description. Once these are settled, we suggest doing a Pre-Sub about as early as key regulatory risks have become clear.

Do you always do Pre-Subs? 🔗

Unless there are time-constraints for the submission and the regulatory strategy is very clear, we do almost always suggest doing a Pre-Sub.

What are typical Pre-Sub subjects? 🔗

At Innolitics, we focus on Software as a Medical Device (SaMD) products. We most typically do Pre-Subs for the following topics:

• Clarifying a regulatory strategy or predicate-device selection
• Requesting feedback on non-clinical or clinical study plans
• PCCP design

In general, we suggest Pre-Subs to de-risk expensive medical-device development activities. Risk is higher when activities are more expensive, take a long time, or there isn’t much FDA guidance on a topic.

What is a Q-Sub? 🔗

The term “Q-Submission” or “Q-Sub” refers to the system used to track a few different types of interactions with FDA. Pre-Sub is a particular type of Q-Sub.

Informational meetings are another useful type of Q-Sub in some cases.

An Informational Meeting is a request to share information with FDA without the expectation of feedback. This information sharing can be helpful in providing an overview of ongoing device development (particularly when there are multiple submissions planned within the next 6-12 months) and familiarizing the FDA review team about new device(s) with significant differences in technology from currently available devices. While FDA staff may ask clarifying questions during an informational meeting, they will generally be listening during the meeting and not prepared to provide any feedback.

You can read more about other Q-Sub types here.

Where can I learn more about Pre-Subs? 🔗

The key FDA guidance is here: 2023 FDA Guidance - Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program

The following podcast episode with Mike Drues includes a lot of great advice for running successful Pre-Subs: June 2021 - Preparing Your Pre-Submission with the Content FDA Wants to See - Greenlight Guru Podcast.

Examples 🔗

TODO: I hope to add some examples of good and bad questions sometime soon!

Revision History 🔗

Date	Changes
2024-04-23	Initial Version