The new article highlights the aspects related to the initial review of submissions, including the stages of the review process.

The Food and Drug Administration (FDA or the Agency), the US regulatory agency in the sphere of healthcare products, has published a guidance document dedicated to the FDA review clock and goals in the context of premarket notification submissions under the 510(k) pathway. The document provides an overview of the applicable regulatory requirements, as well as additional clarifications to be considered by medical device manufacturers and other parties involved in order to ensure proper interpretation of the respective provisions. 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. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing legislation and has been agreed with the authority in advance. 

The scope of the guidance covers, inter alia, the aspects related to the performance goals for 510(k) submissions under MDUFA IV. 

510(k) Performance Goals for MDUFA IV: Key Points 

The guidance describes in detail performance goals applicable with respect to determinations of whether the product in question is substantially equivalent (SE or NSE determinations). According to the document, performance goals are applied to the MDUFA IV cohort of 510(k) submissions and include goals for Substantive Interaction, MDUFA decision, and Total Time to Decision. The document further outlines the key points associated with each of them. For example, the Total Time to Decision is considered to be a shared outcome goal since both the authority and the applicant are responsible for it. The main idea behind this goal is to reduce the average time necessary to make an SE or NSE determination. Thus, the goal describes the overall time the authority requires to review the application, as well as the time the applicant needs to respond to additional requests of the authority. According to the document, it is calculated in calendar days starting from the date a complete submission was received by the authority, and till the MDUFA decision is taken. The document also provides a table showing changes to the review time from 2018 to 2022. 

As explained by the FDA, performance goals initially introduced by the MDUFA IV and then reinstated in MDUFA V include the following ones:

  • Most 510(k) submissions are subject to a user fee, and all 510(k) submissions need a valid eCopy or electronic submission in order to initiate a review;
  • 510(k) submissions are subject to an Acceptance Review before being considered for substantive review;
  • 510(k) submissions are subject to a Substantive Interaction (SI) Goal;
  • 510(k) submissions are subject to a one-tier MDUFA decision goal (for FDA Days and Total Time to Decision); and 
  • For 510(k)s for which the MDUFA decision is exceeded by 10 calendar days, FDA will send a Missed MDUFA Decision (MMD) communication to the submitter. 


The authority also mentions that MDUFA V introduced revised goals for Substantive Interaction, MDUFA decision, and Total Time to Decision. 



As it was mentioned before, in most cases, an applicant would have to pay a user fee associated with a 510(k) submission. Furthermore, each submission has to comply with the requirements for an eCopy or an electronic submission. In this respect, the authority refers to guidance documents dedicated to the eCopy Program and Electronic Submission Template for further guidance.

Acceptance Review 

Under the general rule, once the submission is received, the authority will perform an Acceptance Review in order to determine whether it is complete and can be accepted for the subsequent substantive review. According to the guidance, this should take place within 15 calendar days from the date of receipt. Should the authority decide to reduce to accept the submission, it will notify the applicant within the said timeframe, communicating also the grounds for such a decision – they should be considered by the applicant when making changes to the submission in order for it to be accepted. In such case, the submission will be placed on hold and the review clock will not start until the missing elements are provided. At the same time, the authority additionally emphasizes that such a communication represents a preliminary review of the submission and is not indicative of deficiencies that may be identified later in the review cycle. 

As further explained by the FDA, the approach to be applied with respect to electronic submissions will be slightly different – eSTAR submissions do not require a completeness check since the electronic submission template already incorporates all necessary elements. At the same time, the authority would still apply a technical screening process within the same timeframe of 15 calendar days from the date the submission was received, but not earlier than the respective user fee is paid in full. Should it be identified that the eSTAR submission is incomplete, the authority will inform the applicant accordingly and indicate the information missing. According to the guidance, the technical screening will not impact the review clock since it starts from the date of receipt for the submissions that have passed the said screening. 


Substantive Review 

Upon successful completion of the initial acceptance review, as described hereabove, the authority will commence the substantive review. According to the guidance, during the substantive review, FDA will generally communicate with the submitter through a Substantive Interaction within 60 calendar days of receipt of the accepted 510(k) submission; the Substantive Interaction communication can be an AI request or an email stating that FDA will continue to resolve any outstanding deficiencies via Interactive Review. 

In summary, the present FDA guidance describes in detail the aspects related to the application and submission review process, including the actions to be taken by the authority and the way they will impact the review clock. The document pays special attention to the performance goals set forth under MDUFA IV and V. 



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