Investigational Device Exemptions and the Pre-Submission Program
Depending on the type or classification of your new medical device, you may need to conduct clinical studies to support a premarket approval (PMA) or a premarket notification (510k) with the Food and Drug Administration (FDA). However, before these clinical studies can begin, an investigational device exemption (IDE) from FDA is required. An approved IDE allows a medical device to be used in clinical trials without meeting the usual standards set for marketed devices. FDA encourages clinical trial sponsors to take part in the Pre-Submission (Pre-Sub) program, which allows applicants to obtain FDA feedback prior to a submission and adds transparency to the submission processes. The Pre-Sub program applies to many different types of premarket submissions—eg, IDE, PMA, 510k—as well as certain Investigational New Drug Applications and Biological License Applications. The program can be beneficial for new medical device technologies and for sponsors who are new to the IDE process.
FDA provided a new guidance document in February of this year that explains the details involved in the Pre-Sub program, providing clarification to what was previously an ambiguous process. The new guidance defines the objective of the program, identifies multiple types of requests and meetings, and determines when they should be requested. Through the Pre-Sub program, the sponsor may request Formal Early Collaboration meetings (“Determination Meetings” and “Agreement Meetings”) to seek advice for clinical testing and device development, or the sponsor may request information such as a determination of the study risk (significant or nonsignificant risk). Sponsors may also request “Informational Meetings” to educate FDA about device development or planned submissions.
FDA uses the term “Q-Sub” to refer to the formal written request for feedback. Table 1 provides a listing of the various Q-Sub types that apply to the Pre-Sub process for IDEs, as well as descriptions and timeframes for FDA response.
Table 1. Q-Subs Related to the Pre-Sub Process for IDEs
|Q-SUB TYPE||DESCRIPTION||TIME FRAME FOR RESPONSE|
|Pre-Submission||Feedback in the form of a written response or a meeting or teleconference||Meeting 75-90 days after receipt of request (21 days for urgent public health issues)|
|Informational Meeting||Meeting to inform or educate FDA about ongoing device development or planned submissions without a specific request for feedback||90 days|
|Study Risk Determination||FDA determination of risk classification for planned clinical trials (significant risk or nonsignificant risk)||Not applicable|
|Agreement Meeting||Meeting to reach an agreement on investigational plan, including a clinical protocol||Meeting within 30 days after receipt of request or within timeframe agreed to with sponsor|
|Determination Meeting||Meeting to discuss clinical trial design||Meeting date agreed upon within 30 days of request
FDA determination provided in writing within 30 days following meeting
FDA = Food and Drug Administration; IDE = investigational device exemption
The time from Q-Sub submission to meeting date varies by the type of request. A general timeline is provided in Figure1.
Figure 1. Timeline for “Meeting Request” Q-Sub.
FDA = Food and Drug Administration; RTA = refuse to accept.
Benefits of the Pre-Submission Program
There are many reasons to use the Pre-Sub program. Agreement and Determination meetings are useful for receiving guidance and answers from FDA, and Informational meetings are useful for introducing the company and product to FDA and educating them about a product. According to Barbara Atzenhoefer Stegmeier, Medical Research Manager, Regulatory, at NAMSA, “new novel products will not have one Pre-Sub meeting. It’s a process, and may require a series of Pre-Sub meetings to get the product to the point of submission.” For example, a thorough strategy could include an Informational Meeting to introduce the device, a second meeting to gain feedback on preclinical studies, and further meetings to review the clinical program and how you should approach it.
Tips for the Applicant
The first step to take when preparing for the Pre-Sub program is to get a regulatory professional involved early on and often. “The Pre-Sub process is very strategic in nature,” Ms. Stegmeier noted. “You need to have a seasoned industry clinical research professional involved. Someone who will tell you the truth, who can see the entire landscape, see what kind of data is needed, what standards exist for this type of product . . . someone who is able to look at a product and help identify the key questions to ask the Agency.” In many cases, an experienced regulatory professional can answer a question without going to FDA, which can save time and money that can be better spent elsewhere. “You need to have clearly defined questions. You need to have a strategy,” she added. “You should use [the program] judiciously to get answers from FDA only when the internal team can’t provide the information. A regulatory professional can help you move through these [processes] and form the right questions to ask FDA.”
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