The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of medical devices, has published a guidance document dedicated to acceptance and filing reviews for premarket approval applications (PMAs).

The present document constitutes an updated version of the guidance initially published in May 2003. Due to its legal nature, the guidance itself does not introduce any requirements the industry representatives shall follow but instead provides additional clarifications and recommendations to be considered. Moreover, an alternative approach could be applied, provided that such an approach complies with the applicable regulatory requirements and has been approved by the regulating authority in advance. The FDA also reserves the right to amend the guidance from time to time, should it be necessary to reflect changes in the regulatory framework.

Regulatory Background

Regulation 21 CFR 814.42(e) prescribes the criteria the premarket approval application should meet. The present document provides additional clarifications with regard to the way the aforementioned regulation should be applied in the course of the PMA filing process. 

The Agency states that it intends to focus its available resources on complete applications in order to facilitate the process of placing medical devices on the market, provided that such devices comply with any and all regulatory requirements in terms of safety and effectiveness. Thus, the acceptance procedures described herein are important for the improvement of the overall quality of the applications submitted to the FDA for review. These procedures allow the regulating authority to focus its activity on reviewing the applications that are complete and meet all mandatory criteria.

In order to assist the parties involved in complying with the applicable regulatory requirements, the Agency provides the criteria for acceptance and filing separately. According to the document, during the acceptance review, the regulating authority assesses the completeness of the application submitted and notifies the applicant within 15 calendar days of receipt about any documents that are missing (if applicable). The present guidance also provides a checklist to be used by the applicants when evaluating the completeness of the submission before filing it to the regulating authority. The Agency also mentions that there are no significant changes in comparison to the previous versions of the guidance in terms of the regulatory requirements described. The recommendations the FDA provides herein are also based on the authority’s experience with the submissions filed by the applicants in recent years. 

Another important point highlighted in the guidance relates to the format of the submission. According to the current regulatory requirements, the submission of an eCopy is required. At the same time, the applicant shall also provide a signed cover letter (hard copy). The Agency emphasizes that the submission of a valid eCopy constitutes an important prerequisite for the application to be reviewed. 

Acceptance and Filing Review in Detail

According to the document, the PMA acceptance and filing reviews are intended to determine whether the application submitted by the interested party is complete from an administrative standpoint, so the regulating authority could proceed further with the substantive review. 

The Agency also outlines the cases when under the applicable regulation (21 CFR 814.42(e)) it is allowed to refuse, namely: 

1. The PMA is incomplete because it does not on its face contain all the information required under section 515(c)(1)(A)-(G) of the FD&C Act.

2. The PMA does not contain each of the items required under section 814.20 and justification for omission of any item is inadequate. 

3. The applicant has a pending premarket notification under section 510(k) of the FD&C Act with respect to the same device, and FDA has not determined whether the device falls within the scope of section 814.1(c).

4. The PMA contains a false statement of material fact.

5. The PMA is not accompanied by a statement of either certification or disclosure as required by 21 CFR Part 54. 

The aforementioned regulation also prescribes the scope of information to be provided by the applicant. The information provided should be sufficient for the regulating authority to make a decision on whether the application should be approved or rejected. 

The present FDA guidance is intended to provide additional clarifications on the criteria to be applied by the Agency in terms of accepting and filing a premarket application. As mentioned before, the document contains a checklist similar to the one used by the FDA when making such a determination. The decision to be taken by the Agency on the basis of the information received include:

– “Accept”, or

– “Refuse to Accept” (RTA), and

– “File”, or 

– “Not to File”. 

It is important to mention that the procedures described herein do not affect the general review process and timelines. The scope of the guidance also does not cover the aspects related to the applications submitted under the Breakthrough Devices Program as they are described in separate guidance dedicated thereto. The FDA also refers to the appropriate guidance on Q-submissions, which should also be considered by the parties involved. According to the document, the applicants are encouraged to have meetings with the FDA representatives before submitting their applications in order to clarify all important aspects in advance. 

Review Policies and Procedures

The present FDA guidance provides the review policies for both acceptance and filing. The aforementioned review policies are provided separately in order to ensure clarity for the parties interested in submitting the PMA.

At the very first stage, the regulating authority will access the completeness of the application submitted and its compliance with the applicable requirements using the checklist provided in the guidance. Under the general rule, all the necessary elements should be in place unless there is a sufficient justification in place for each of the elements that are absent. As mentioned before, the acceptance review should take up to 15 calendar days from the date the initial application has been received by the regulating authority. The FDA also emphasizes that the acceptance review described herein will commence only upon payment of the applicable fee. 

Should the application be found complete, the Agency will notify the applicant about the acceptance and initiate the filing review. It is important to mention that if the regulating authority would not complete the acceptance review in time, the applicant should be considered accepted by default. 

If at least one of the mandatory elements indicated in the checklist is not present in the application submitted, the FDA shall render a “Refuse to Accept” determination and notify the applicant accordingly. The communication provided by the FDA should contain the indications of the particular elements of the application that are missing. In order to restore compliance with the applicable requirements, the applicant may submit the information requested using the same PMA number.

In summary, the present FDA guidance provides additional clarifications with regard to the criteria to be applied by the regulating authority when evaluating the completeness of the application submitted. The document highlights the most important aspects to be considered by the applicant in order to facilitate the review. 

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