The new article highlights the aspects related to the main types of requests to be applied depending on the situation and review stage.
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The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a revised guidance document dedicated to the requests for feedback and meetings for medical device submissions under the Q-Submission program. The said program allows medical device manufacturers to request and obtain feedback from the authority before submitting the main application for marketing approval related to a medical device intended to be placed on the market. Such an approach is expected to facilitate and streamline the regulatory procedures associated with the new products, as well as to improve the overall quality of applications and, consequently, reduce the review burden for the authority.
It is important to mention that FDA guidance documents are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations, but rather to provide additional clarifications regarding the existing regulatory requirements, as well as recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance thereto. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing regulatory framework and has been agreed with the authority in advance.
The document describes in detail various types of requests and highlights the key points associated with each of them.
Submission Issue Requests (SIRs)
According to the guidance, a submission issue request stands for the one that is submitted to obtain feedback from the authority in writing or during the meeting with respect to the way the issues outlined in a marketing submission hold letter should be addressed. This type of requests also applies to CW hold letters, IDE letters, or IND Clinical Hold letters. In particular, for the purpose of this guidance, the concept of a marketing submission hold letter covers the following:
- Additional Information Needed for 510(k)s, De Novo requests, Cos, and Duals;
- Major Deficiencies, Not Approvable, Approvable with Deficiencies, Approvable Pending GMP, and Approval with PAS conditions for PMAs and HDEs;
- Complete Response Letter for Biologics License Applications (BLAs).
As further explained in the guidance, this type of requests is intended to facilitate interaction between the authority and the applicant in order to ensure the issues raised by the authority are addressed in a timely and efficient manner so the regulatory procedure could continue, making sure the applicant is able to address all the questions pending in the appropriate formal response. Requests of this type could be used to initiate a discussion on the approach to be applied for addressing the issues identified by the authority. At the same time, the FDA additionally emphasizes that a SIR should not be used to request that FDA pre-review an intended formal response to assess adequacy. Furthermore, the authority also mentions that the applicant shall provide an official response to a deficiency letter issued by the authority within the timeframes set forth by the respective regulation irrespective of a SIR submitted. Neither this approach could be used to discuss final determinations made by the authority (e.g., Not Substantially Equivalent, Withdrawal or Deletion).
If the issue in question is relatively simple, there is no need to submit a SIR to obtain clarification on it – such questions could be discussed with the lead reviewer without the management involved. Neither such requests are needed in case of issues related to the file which is under active review.
Study Risk Determination
Another type of request described in the present guidance relates to the risks associated with the studies. According to the guidance, a Study Risk Determination is a request for FDA determination for whether a planned medical device clinical study is significant risk (SR), non-significant risk (NSR), or exempt from IDE regulations as defined by the IDE regulations (21 CFR part 812). The authority also mentions that in case of studies that are not covered by the scope of the abovementioned exemption, medical device manufacturers will be responsible for making the initial risk determination to be communicated then to the Institutional Review Board (IRB). In this respect, the authority refers to a separate guidance document dedicated to significant risk and nonsignificant risk medical device studies. It is stated that (a) the authority is able to assist the interested parties in making the proper determination, and (b) the determination made by the FDA will be final and non-negotiable, so all disputes regarding the said determination should be finally resolved by the FDA.
The scope of the guidance also covers the aspects related to requests for informal meetings to be carried out to share information with the authority without expecting any feedback from the latter. Such an approach could be applied in case of providing additional information regarding the ongoing device development process to make sure the authority’s review team is familiar with the new device and the main differences in terms of technologies used in comparison to similar medical devices already placed on the market. The authority reserves the right to request additional information and clarifications, even though the FDA representatives are usually listening during such meetings.
This category also applies to interactions between the authority and the applicant in case such interactions are not covered by any of the other categories.
In summary, the present FDA guidance describes in detail certain specific types of requests and highlights the key points to be taken by medical device manufacturers in this respect. The authority explains specific cases when such requests could apply, and also provides references to related guidance documents.
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