The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published several guidance documents dedicated to the De Novo Classification Process. One of the documents provides a brief overview of the applicable regulatory framework, as well as additional details on submissions and the whole classification process in general. The present guidance addresses the matters related to acceptance review – a stage of the process when the FDA determines the admissibility of a De Novo request submitted. According to the applicable regulatory requirements, an acceptance review should be always conducted before a substantive review. 

Due to their legal nature, guidance documents issued by the FDA contain non-binding provisions intended to assist medical device manufacturers and other parties involved in interpreting the regulatory requirements and ensuring compliance thereto. However, an alternative approach could be applied, provided such an approach complies with existing legislation and has been agreed with the authority in advance. 

The present document constitutes an updated version of the respective FDA guidance initially published earlier in September 2019. 

Regulatory Background 

According to the guidance, Subpart D of the regulation 21 CFR 860 prescribes the particular approach to be applied by the FDA when determining whether a De Novo request meets formal requirements before commencing the substantive review. The present document is intended to provide additional clarifications concerning the information such a request should contain to meet the aforementioned admissibility criteria. It is stated that following such an approach would allow the regulating authority to focus its resources on complete requests and, consequently, facilitate and accelerate the review of such requests, and also improve the effectiveness of relevant regulatory processes in general. Providing such information to medical device manufacturers interested in submitting De Novo requests would also improve the transparency of the De Novo classification process. 

First of all, the authority mentions that the aspects related to acceptance review do not impact the process of substantive review and the final decision taken. However, these aspects are important in the context of determining the review timetable – as it was mentioned in the previous article, once the authority identifies that certain information, which is important for review, is missing, it would request such information from the applicant, while the latter would have limited period time to provide the information requested, otherwise the De Novo request subject to review would be deemed withdrawn. Hence, during the acceptance review, the FDA examines the completeness of a De Novo request submitted to determine its admissibility for substantive review. The present document describes in detail the approach to be applied by the Agency when making such a determination, as well as the particular criteria used. 

Acceptance Review Policies and Procedures 

According to the guidance, when conducting an acceptance review, the FDA will follow the appropriate Acceptance Checklist outlining the scope of information a complete De Novo request should contain. Should the Agency identify that the request submitted fails to meet the applicable criteria, it is entitled to refuse to accept it. It is further stated that for the De Novo request to be accepted, all items identified as elements of a complete De Novo request (“RTA items”) in the Acceptance Checklist should be present or a rationale should be provided for those elements determined by the requester to be not applicable. Moreover, the Agency recommends the applicants complete the appropriate checklist themselves and submit it together with the De Novo request. In such a case, additional references to the particular documents should be provided. 

Under the applicable regulations, the FDA shall complete an acceptance review within 15 calendar days from the date the request has been initially received. The authority additionally mentions that an acceptance review would commence only once the appropriate fees have been paid by the applicant in full, and provided a valid eCopy has been submitted. 

It is also important to mention that the scope of an acceptance review covers only the documents initially submitted by the applicant when filling the first De Novo request. Hence, all additional information submitted by the applicant concerning the request after it has been accepted for a substantial review should not be subject to acceptance review. 

Acceptance and Refusal

According to the guidance, the FDA has certain flexibility in determining the actions to be taken in case certain information is missing: depending on the nature of such information and its importance for further review, the Agency may either refuse to accept the De Novo request or require the applicant to provide such information. Such a determination should be made by the FDA on a case-by-case basis. Should the authority decide to reduce to accept a De Novo request submitted, it will duly inform the applicant about the decision taken and provide clarifications on the reasons behind such a decision. The appropriate notice would be also accompanied by a copy of the completed checklist. In response to such notice, the applicant may provide the information and documentation that is missing. In such a case, submission of a new De Novo request is not required. However, if, in the opinion of the FDA, the information that is missing is critical, the authority may require a new request to be submitted. Should the applicant fail to submit a complete request within 180 days from the date the notice has been provided by the FDA, the request would be deemed withdrawn. 

Once additional information has been received, the regulating authority would commence an acceptance review from the very beginning, and the same timeline of 15 calendar days should be applied. During such a review, the authority will examine the completeness of a supplemented submission to determine whether it now meets all applicable acceptance criteria. 

Should the authority determine the De Novo request as complete, it will duly notify the applicant and commence the substantive review. According to the guidance, if FDA does not complete the acceptance review within the acceptance review period (i.e., within 15 calendar days of receipt), FDA will accept the De Novo request for review and will notify the requester (21 CFR 860.230(b)). It is also important to mention that even after deciding to accept the De Novo request for the substantial review, the FDA may request the applicant to provide additional information. 

In summary, the present FDA guidance provides an overview of the principles applied by the FDA when conducting an acceptance review of a De Novo request. The document also clarifies the approach to be followed by the regulating authority in case certain information is found missing.

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