Within any industry, if you ask poor questions, you will often get poor answers. This is especially true for the medical device industry and more specifically, for product manufacturers seeking feedback from the U.S. Food & Drug Administration (FDA). Simply put, asking better questions can assist device organizations to identify and solve potential device errors, pinpoint the best-fit regulatory strategy, and discover information that leads to more efficient product development.
Obtaining Actionable Regulatory Feedback
One way in which device manufacturers can obtain targeted feedback is by asking questions of the FDA through its Pre-Submission (Pre-Sub) Program. This option allows medical device and in vitro diagnostic (IVD) organizations to gather very specific feedback related to regulatory activities.
More often than not, a Pre-Sub meeting is the first touch-point and primary introduction of an organization’s device to the FDA. These meetings offer a unique opportunity for manufacturers to provide clarity to the regulatory agency regarding the technology under review, which often results in directed and actionable FDA responses.
Typically, Pre-Sub gatherings include a discussion of the FDA’s feedback on any proposed bench, pre-clinical or clinical programs that are intended to support a device’s intended regulatory strategy. Another point of conversation includes that of any pre-selected predicate device and the appropriateness of the associated product.
But, while the Pre-Sub Program is intended to be beneficial, device manufacturers frequently make common mistakes along the way, the biggest of which involves poorly developed meeting questions. Unfortunately, this often results in a missed opportunity for device organizations to maximize what little time they have with the FDA.
As a result of NAMSA’s deep-rooted experience and involvement with the FDA over the course of several years, our regulatory experts have found that Pre-Sub meetings are most valuable when an organization is equipped with well-developed questions that allow the FDA to provide meaningful, actionable feedback. Essentially, the questions posed should have grit, purpose and provide the required information that can assist in procuring meaningful feedback.
For example, there is an impulse to provide the FDA with brief and superfluous device descriptions, vague or scant information on the mechanism of action, and data regarding what makes the device unique. A device manufacturer simply provides the FDA with the “right” information in hopes of getting the “right” feedback in return. In actuality, one should develop the “right” questions to receive correct and factual feedback…feedback that – if used correctly – can save millions of dollars and significant time throughout the development lifecycle.
Pre-Submission Question Development
As a rule, questions posed of the FDA should follow a “Blue Book” mindset. Questions should be directed and include information that:
- is detailed and specific
- provides device background
- offers device evidence
- states any device concerns or problems
- discuss previous development programs and associated results
- includes justification of the intended regulatory strategy
Provided below are examples of meaningful Pre-Submission meeting questions. These demonstrate real-world scenarios and draw upon NAMSA’s regulatory expertise and 50-year history of strong partnerships with the FDA.
“Are the proposed biocompatibility studies sufficient to support the clinical trials?”
“The biocompatibility testing for the device is based on the testing recommended for a limited blood contacting device as listed in the Pre-Submission section. We plan to forgo the carcinogenicity testing as the device is manufactured based on the industry standard for materials and utilizes standard manufacturing processes. Does the FDA agree with this approach?”
“Does the FDA agree that the De Novo pathway is appropriate for this device?”
“A search of the FDA database identified no predicates for our device, and it is a low-risk product. As such, we believe that our device is a candidate for the De Novo request based upon the fact that:
- our device is constructed of common materials (water and salts);
- biocompatibility for this product has already been established;
- safety outcomes from the initial Good Laboratory Practices (GLP) report are confirmed; and
- safety and effectiveness have been proven based on clinical studies of more than 2,000 patients.
Given the supportive evidence, does the FDA agree that the correct regulatory pathway for this device is a De Novo submission?”
“Does FDA agree with the proposed predicate we have identified?”
“The purpose of the primary predicate is to demonstrate that the Alpha Graft is substantially equivalent to the predicate. The primary predicate selected reflects the device that is most similar to Alpha Graft in terms of indication for use and technology (absorption over time). Our reference predicates have also been identified to establish equivalence to other 510(k)-cleared devices that have similar technology or indications for use.
In Section 3 of the Pre-Submission form, we have compared and contrasted the Alpha Graft to already cleared graft material. We believe that this material is an appropriate predicate. Might the FDA have any other suggestions for a predicate device?”
“Does the FDA agree with the proposed Modular Pre-Market Approval (PMA) strategy?”
“We have proposed to submit three PMA modules as identified in Section 5 of the Pre-Submission packet.
- The first module is to include pre-clinical testing such as biocompatibility, sterilization, and bench testing; this is to be completed and available for submission by June 2018.
- The second module will include manufacturing information.
- The third module will be completed after the clinical data is finalized, and will consist of literature, U.S. data and OUS data, as discussed in Section 6 of the Pre-Submission packet.
- We propose the utilization of literature to support the application of the device to individuals up to 85 years of age.
- U.S. and OUS data was collected using similar protocols to the predicate device and with identical inclusion/exclusion criteria. As such, we will present these data as identified in the IDE G17XXXX.
- We will also present complaint and sales data for the device, as the product has been commercially available in Canada since 2017.
Does FDA agree with this approach for module three?”
As demonstrated above, asking “good” questions of the FDA allows the opportunity for device manufacturers to receive “good” feedback…feedback that is factual, meaningful and actionable.
NAMSA is the industry leader in driving successful Pre-Submission meetings. Our team of regulatory, statistical, quality, pre-clinical, and clinical Associates have countless years of experience working for – and with – the FDA and understand how to obtain the most meaningful feedback that leads to accelerated submissions and product approvals.
If you are interested in speaking with us about FDA-related activities and regulatory strategies, please contact us at: firstname.lastname@example.org or 1-419-666-9455.
Angela Mallery, EdD, is a Principal Product Development Strategist at NAMSA with over 25 years of experience working in device regulatory affairs in small, medium, and large sized companies. Angela has experience in project management, regulatory strategies, pre-submission meetings; and has hands-on experience developing, writing, and receiving clearance/approval for 510(k), IDE submissions and reports, PMAs, CEP/CERs, and Technical File/Design Dossier submissions. Angela’s therapeutic experience includes cardiology, neurology, peripheral vascular devices, general surgical devices and orthopedic implants.