5 Steps to Prepare for an Early and Informative Q-Sub with FDA

Many organizations believe that the Q-Sub process should be completed after a design is relatively mature. The belief is that sufficient technical detail needs to be shared to gain substantive feedback from FDA. 

Despite this conventional view, there can be significant benefit in completing the Q-Sub process before the formal design process starts. An early Q-Sub can provide insight that will inform the product development plan, test methods, clinical validation requirements, and much more.

However, to effectively complete the Q-Sub process, preparations are required. Below are 4 steps to get ready for an early and informative Q-Sub with FDA.

1. Create the preliminary "label"

Of critical importance to FDA is answering these questions: 

• Who is it for?  In other words, what are the "Clinical Indications." Who are the operators of your device? And who are the patient populations that your device aims to benefit? Are there specific disease states for whom the device may be applicable? Are there particular organs that will be targeted? As part of your product labeling, you must carefully define answer these questions. For 510(k) devices, many of these questions will be informed by the predicate that is selected.  
• What is it for?  This is the essence of "Intended Use," a common term that is frequently used (and misused) in the medical device industry. In your Q-Sub, you need to clearly state what is expected by using your medical device. Often, this is combined with the "Clinical Indications." The same device when used for very different "Clinical Indications" may introduce varying levels of risk. Consider a scalpel. It can be used for a general indication as a cutting implement. Alternatively, the same scalpel could be used for a specific indication in high-precision ophthalmology procedures. The intended use for these two indications would be very different. Accordingly, the regulatory pathways and testing requirements would also be very different.
• How does it work?  This is effectively your "Instructions for Use", also known as IFUs. Teams sometimes make the mistake of diving into technical details that specify the functionality of the product. Instead, what is of primary concern to FDA is the how users will interact with a medical device. What are the steps required to set-up, operate, dispose, clean, evaluate? Often, your IFUs will be storyboard illustrations that walk through the expected user process from beginning to end. Mapping out these steps will help you think through the use case of your medical device, and it will help FDA do the same. Creating a preliminary IFU before the product has been designed is a great practice regardless of whether you aim to engage in the Q-Sub process. 

2. Create a comparison table with predicates and references

When you believe that the 510(k) pathway is suitable for your medical device, you need to build a comparison table. Within this comparison table you will capture Clinical Indications, Intended Use, technical specifications, operating conditions, and other details that are published as part of your predicate's regulatory labeling and other marketing and promotional materials. 

Sometimes, you may aim to combine the clinical indications and/or intended uses from two or more predicate medical devices. In these cases, you will need to add multiple predicates to this comparison table. Additionally, comparison tables may also include reference devices, which may be helpful in justifying technical differences (Step 3).

Comparison tables aren't just for 510(k)s though. They can also be helpful for De Novo and PMA pathways. Listing reference devices that have similar Clinical Indications and/or Intended Uses may help you and FDA define understand how critical risk factors have been be evaluated and mitigated by similar medical devices.  

3. Create justifications for technical differences

Your device may be equivalent to the listed predicate and/or reference devices in certain regards. However, there are likely to be other aspects of your device that are different from the predicate and/or reference devices. In these cases, it is helpful to describe the technical differences and determine if these technical differences may impact safety or effectiveness. Below are a couple of examples related to technical differences and their associated justifications for safety and effectiveness.

• Example 1: A surgical sealant applicator that uses compressed gas to dispense a hydrogel. (Predicate - A surgical sealant applicator that uses a manual trigger to dispense a hydrogel.) In this example, the power source would be listed on the comparison table as "compressed gas" for the proposed new medical device and "human power" for the predicate. The technical difference may be justified by defining the means for equivalent precision and dispensing control that will be afforded by the compressed gas source, in comparison to the human actuation as in the predicate device. Additionally, this technical justification may point toward specific verification and validation testing, such as force to activate testing, dispense accuracy accuracy, and summative human factors testing. 
• Example 2: A cardiovascular shunt that can be expandable to accommodate growth in pediatric populations. (Reference - Non-expandable cardiovascular shunts used in cardiac bypass surgeries.) A key technical difference would clearly be the expandable nature of the cardiac shunt in comparison to the non-expandable cardiac shunt. Justifications may include that identical materials are being utilized and comparable surgical procedures will be completed. The evaluation and risk mitigation strategies may include testing the controlled rate of expansion through bench studies, animal studies, and eventually clinical studies.

4. Create a high-level test summary

Many tests will be defined by standards that are applicable to a particular product code. These tests and standards should be listed in a high-level test summary table. Additionally, you will have unique tests that may be required based on the justifications of technical differences described in Step 3. Providing FDA with a summary of your test plans will serve as a valuable opportunity to collect feedback on these plans.

Of particular importance is gaining feedback on the pre-clinical data needed to open investigation device exemption (IDE) studies, when applicable. Providing details around the proposed pre-clinical endpoints, sample size, and other study design elements may allow FDA to provide comments on this critical evidence approach.

FDA may not be able to provide specific guidance on pre-clinical and clinical study design requirements until more detailed protocols have been drafted. However, early feedback on the types of tests and the relative scope of tests is extremely valuable insight to gain during the early-stage. This data may inform timelines, resources required, and capital needed to complete these processes.

Often, the Q-Sub process is multi-stage. There is nothing that prevents you from holding numerous Q-Sub meetings with FDA prior to your regulatory submission. Holding an early Q-Sub will help you gain clarity on the topics listed above, which will reduce the risk of holding false assumptions around pathways, predicates, clinical studies, and more. As you progress through the design process, subsequent Q-Sub meetings can help you refine your clinical and regulatory strategy further. Consider it an iterative process.

5. Carefully design your questions for FDA

The term "design" listed in Step 5 is intentional. The questions that you ask FDA in your Q-Sub must be carefully written to elicit clear and specific responses while ensuring that your points-of-view are being considered. Going into a Q-Sub expecting FDA to tell you what to do is a mistake. FDA's representatives will only react to specific questions that are presented.

When you are designing your questions, you should focus on the specific assumptions and/or risks that you believe exist with your new medical device. Sometimes, there is hesitancy to touch on these topics during Q-Subs, believing the FDA's comments may negatively affect the eventual application review process. But, getting the agency's reaction early will give you time to adapt. Deferring feedback on these critical regulatory components may introduce a huge redo loop late in the game that will devastate your timeline and budget. Much better to get this critical feedback early and gain the opportunity when the costs of doing so are low. 

When you are designing these questions for your Q-Sub, you will want to first provide ample background material to help FDA gain context and share your point-of-view on why you believe a particular pathway, predicate, testing methodology, or other regulatory detail is appropriate. Your question then effectively becomes, "Does FDA agree with ..."  

This article defines Step 5 as "Carefully design your questions for FDA." However, these questions should actually be your first step in preparing for the Q-Sub process. They should cover the most critical regulatory aspects of your device and the assumptions that may end up setting you back if you don't get the right clarification early.

After you design these questions, you should then build out the background information, instructions for use, and other materials to support your points-of-view. This includes development of the right visuals, summaries of your predicate and reference device research, and detailed arguments for your justifications and risk mitigation strategies pertaining to any technical difference and/or residual risk that exists.

The Q-Sub process can be daunting, but it's one of the best mechanisms that companies can leverage to ensure that the regulatory strategy is sound and the key assumptions are clarified. Conducting the Q-Sub process at the early-stage can inform your product development plan and ensure that you have the right check-points and tests in-place to collect the necessary evidence that will support your eventual regulatory submission.

The key in effectively conducting the Q-Sub process is to invest the time and resources in preparing the materials that best position your device and your intended regulatory strategy. If you could use support in preparing for and facilitating your next Q-Sub, reach out to Archimedic for support.