The article provides an overview of the regulatory requirements related to the actions to be taken by the authority and/or applicant in the context of premarket notification, and the effect such actions will have on the review timelines.
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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 guidance document dedicated to the effect the FDA and industry actions on 510(k) premarket notification submissions will have on FDA review clock and goals. The document provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered by medical device manufacturers and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. The authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the applicable legislation and has been agreed with the authority in advance. The present document constitutes a revised version of the respective guidance initially issued by the authority earlier in May 2004.
Regulatory Background
In accordance with the existing legislation, the authority is entitled to collect user fees for the review of certain premarket submissions including, inter alia, premarket notification submissions. These funds will be used by the authority to improve the review process and achieve certain performance goals.
The scope of the guidance covers the following aspects:
- The different FDA actions that may be taken on premarket notifications (510(k)s);
- The effect each action has on goals under the Medical Device User Fee Amendments of 2022 (MDUFA V) for 510(k)s received in FY 2018-2022;
- The effect each action has on goals under MDUFA V for 510(k)s received in FY 2023-2027; and
- The different industry actions that may be taken on 510(k)s.
As it was mentioned before, recommendations provided by the authority in guidance documents it may issue from time to time are non-binging in their nature and do not establish legal obligations, but are rather intended to assist the industry in interpreting the requirements set forth under the existing regulatory framework. The authority also reserves the right to make changes to the guidance document and recommendations provided therein, should such changes be reasonably necessary to reflect corresponding amendments to the underlying regulations.
FDA Actions: Key Points
First of all, the authority describes the actions it may take with respect to premarket notification (510(k)) submissions. Under the general rule, the authority will commence a substantive review of such a submission once it was established it meets the applicable refuse to accept (RTA) criteria described in the respective guidance document issued by the FDA, or passes the initial screening – in case of electronic submission using the electronic Submission Template and Resource (eSTAR). Once the submission is received, the authority will verify the submission type is correct. Should it be identified that the submission type used by the applicant is incorrect, the authority will place the review on hold, providing the applicant with the possibility to change the submission type. According to the guidance, in such a case, the review clock will begin on the date the submission of a correct type was assessed by the authority and passed the preliminary review. As further explained in the document, upon completion of a substantive review, the authority may take one of the following actions:
- Issue an order declaring a device substantially equivalent (SE) to a legally marketed predicate device (SE letter);
- Issue an order declaring a device not substantially equivalent (NSE) to any legally marketed predicate device (NSE letter);
- Issue a request for additional information (AI request); or
- Advise the submitted that the 510(k) submission is not required (i.e., the product is not regulated as a device or the device is exempt from the premarket notification requirements of the FD&C Act).
The authority also mentions that should the applicant fail to provide the information requested within 30 days from the date of the respective request, the submission will be considered withdrawn, and a notice of withdrawal also referred to as a “deletion letter” will be served to the applicant. In this case, the term “deletion” is used to distinguish such cases from the ones where submission was withdrawn upon request of the applicant itself. It is also important to mention that the timeframes for a request for additional information could be subject to extension.
The first and second actions listed hereabove, namely issuing an SE letter and issuing an NSE letter are considered MDUFA decisions. The document further describes each of them in detail.
An Order Declaring a Device SE
According to the guidance, an order declaring a device to be SE (SE letter) is a letter issued to the 510(k) submitter stating that FDA has determined that the device described in the 510(k) submission is substantially equivalent to a legally marketed device. Such an order establishes that the device in question is allowed for marketing and use in the US. When making such a determination, the authority will consider the respective criteria set forth under the FD&C Act and 21 CFR 807.100(b).
In terms of the review clock, such a decision taken by the authority is considered to be a final action and shuts off the review clock.
An Order Declaring a Device NSE
The document further describes an order declaring a device to be NSE (NSE letter), which stands for a letter issued to a 510(k) submitter stating that FDA has determined that the device described in the 510(k) submission is not substantially equivalent to any legally marketed device and may not be introduced into commercial distribution in the U.S. In accordance with the applicable regulations, such a letter could be issued in the following cases:
- There is no similar medical device already allowed for marketing and use (predicate);
- The intended use of a new device is different from the intended use of a predicate device;
- The technological characteristics of the device in question raise different questions related to safety and effectiveness;
- There are reasons for the authority to determine that the device is significantly different in terms of technical characteristics and intended use, preventing the authority from determining a substantial equivalence.
As in the case with the SE letter, this action is considered to be final and shuts off the review clock.
In summary, the present FDA guidance provides an overview of the regulatory requirements in terms of the review clock. In particular, the document explains the impact various actions taken by the authority will have on the review clock.
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