The 510(k) Review Process: From eSTAR Submission To Substantial Equivalence Decision

How a 510(k) moves through FDA: from eSTAR to decision

A Traditional, Abbreviated, or Special 510(k) travels a defined path from submission preparation to a substantial equivalence determination. This overview walks through the four operational stages a reviewer works within: preparing and transmitting the eSTAR, the Refuse to Accept (RTA) acceptance screen, substantive review with its Substantive Interaction milestone, and the Additional Information (AI) hold, together with the MDUFA V performance goals and calendar timelines that govern each step.

Stage 1: eSTAR preparation and transmission

eSTAR ("electronic Submission Template And Resource") is FDA's electronic submission template, built as a structured dynamic PDF that guides the preparer through assembling a complete electronic submission. It collects structured data through fields, dropdowns, and checkboxes while accepting unstructured supporting material (documents, PDFs, images, video) as attachments ¹⁰. For 510(k)s it is the only currently available electronic submission template, and its use became mandatory in October 2023; before that, use was voluntary during a defined transition period ^10241220.

Several design features shape the submission before it ever reaches a reviewer:

• Guided, logic-driven assembly. eSTAR uses questions, prompts, targeted data requests, integrated FDA databases (product codes and recognized consensus standards), and links to regulations and guidance to guide construction of a complete 510(k) ¹⁰.
• Reviewer-aligned organization. It assembles the submission in a format that closely follows FDA's internal SMART 510(k) review memo template, so the content maps to how the reviewer will work through it ¹⁵.
• Conditional content requests. It prompts for supporting documents based on the answers given; for example, if clinical testing is indicated, it automatically requests the clinical-testing documents and the applicable financial certifications or disclosures ¹⁰¹⁵.
• Automated completeness check. Once all necessary sections are completed correctly, the PDF displays the status "eSTAR Complete," and the CDRH Portal automatically verifies completeness on receipt ¹²¹⁵.

Because eSTAR enforces this structure up front, a complete eSTAR is exempt from the Refuse to Accept process. Instead, after receipt and payment of the user fee, FDA performs virus scanning and technical screening, anticipated within 15 days, to confirm that template responses accurately describe the device and that each applicable attachment question has at least one relevant attachment. If screening fails, FDA identifies the missing information and places the submission on hold pending a complete replacement eSTAR ¹⁵.

Stage 2: Refuse to Accept (acceptance) screening

For submissions subject to it, the RTA process is an administrative acceptance review conducted before substantive review to determine whether the 510(k) is sufficiently complete for FDA to begin substantive review. It assesses the presence of required information, not the quality or adequacy of the data supporting substantial equivalence ⁶⁹⁷⁸. The policy applies across device types and uses the checklist matching the 510(k) type: Traditional, Abbreviated, or Special ⁶⁹⁵⁶⁸².

Preconditions and timing. FDA will not begin acceptance review until the applicable user fee is paid (or an exception applies) and a valid eCopy or eSTAR has been received ⁴⁶⁷. FDA should complete the acceptance review within 15 calendar days of Document Control Center (DCC) receipt ⁸². A government closure during that window may extend the period by a comparable number of business days ⁴⁶⁷.

What FDA checks. The reviewer first works through preliminary screening questions (an internal tool submitters are not expected to address), such as whether the product is a device under section 201(h) of the FD&C Act or a combination product with a device constituent subject to 510(k) review; an uncertain or negative answer triggers consultation with product-jurisdiction personnel ⁷⁰⁷¹. FDA then verifies that each element designated an RTA item on the applicable checklist is present, or that a rationale for its omission is provided ⁵⁶⁷¹⁸². Key operating rules:

• For checklist questions offering "Yes," "No," or "N/A," the item generally must be answered "Yes" or "N/A" for acceptance ⁷⁴.
• FDA assesses only whether an element is present or has a stated rationale, not whether it is adequate; if information is present but incomplete, FDA generally marks the item "Yes" and addresses adequacy during substantive review ⁷⁴⁷⁷⁸⁴.
• Organizational elements (table of contents, labeled sections, page numbering, 510(k) type) should not by themselves cause an RTA ⁷⁷.
• FDA retains discretion to seek a missing item interactively when time permits before the 15-day deadline rather than issuing an RTA ⁵⁶⁷⁷.

Notification outcomes. Within 15 calendar days of DCC receipt, FDA electronically notifies the designated contact that the submission is (1) accepted for substantive review, (2) Refused to Accept, or (3) under substantive review because FDA did not complete acceptance review in time. The notice identifies the FDA lead reviewer (or, at CBER, the regulatory project manager), and acceptance or RTA determinations require supervisory concurrence ⁵⁷. If FDA issues an RTA, it provides the completed checklist identifying the specific missing elements, and the submission is placed on hold with the review clock stopped until the missing elements are supplied and the submission is accepted ⁵⁶⁴⁶⁷.

Responding to an RTA. The submitter responds under the original 510(k) number without a new submission or new user fee, and generally needs to supply only the requested information rather than the full submission (unless most of it is missing or not in English) ⁶⁷⁵⁶. FDA performs a fresh acceptance review of the response within 15 calendar days ⁶⁷. If FDA does not receive a complete RTA response within 180 days of the RTA notification, it considers the 510(k) withdrawn and closes it ⁶⁷.

Clock implications. If the original 510(k) is accepted on first review, the review clock starts on the DCC receipt date; if initially RTA, it starts on the DCC receipt date of the information that results in acceptance. The clock does not run during user-fee hold, eCopy hold, or RTA status. If FDA does not finish acceptance review within 15 days, the submission enters substantive review and the clock starts on the DCC receipt date of the most recently received information, with those acceptance-review days (up to 15) counted inside the 60-day Substantive Interaction goal ⁵⁷⁶⁷.

Stage 3: Substantive review and the Substantive Interaction milestone

Once a submission is accepted (or, for an eSTAR, passes technical screening), FDA begins substantive review. For an eSTAR that passes screening, the clock starts on the receipt date and the screening time does not affect it; if FDA determines the submission type is incorrect, it holds the file until the correct type is received and passes screening ⁶⁶²⁹.

The defining early milestone is the Substantive Interaction (SI). During substantive review, FDA generally communicates with the submitter within 60 FDA days of receipt of the accepted 510(k). The SI takes one of two forms ²⁹⁵⁸:

• an Additional Information (AI) request, which places the file on hold and identifies deficiencies that must be resolved for review to continue; or
• an email stating that FDA will continue through Interactive Review, resolving outstanding deficiencies without placing the file on hold.

An SE letter issued before the SI goal date also satisfies the SI goal ²⁹. After the SI, FDA intends to use Interactive Review to reach its MDUFA decision ²⁹.

The MDUFA V performance goals (FY 2023 to FY 2027, each at a 95% performance level) are an SI within 60 FDA days and an SE/NSE MDUFA decision within 90 FDA days ³. "FDA days" count only FDA's review time; the clock stops while the submitter prepares a response to an AI request, which is why total elapsed time exceeds 90 days when additional information is requested ¹.

Stage 4: Additional Information requests and the hold

FDA issues an AI request during substantive review when the submission lacks information needed to decide substantial equivalence (SE) or not substantial equivalence (NSE), and that information is not suitable for Interactive Review or cannot be provided quickly enough to avoid undue delay without a hold. The request is issued by email with an attachment identifying the deficiencies ³⁶.

An AI request is a formal interim action distinct from an Interactive Review request. It places the 510(k) on hold effective on the request's issue date, stops the 90-FDA-day review clock, and ends that review cycle. A complete response addressing all identified deficiencies allows the clock to resume on FDA receipt ³⁶³⁵. If FDA finds the response incomplete because one or more deficiencies remain unaddressed, it terminates the review cycle, notifies the submitter by email, and returns the 510(k) to hold as of the original AI-request date, treating the clock as never having resumed ³⁵.

Although 21 CFR 807.87(l) allows FDA to consider a 510(k) withdrawn after 30 days without additional information, FDA intends to automatically allow up to 180 calendar days from the AI request date, with no written extension request required. FDA intends to issue a notice of withdrawal if it does not receive a complete response addressing all AI deficiencies within that 180-day window ³¹⁴⁹.

Timelines: FDA days versus total calendar time

The two clocks that matter most are FDA's review-day goals and the average Total Time to Decision, which is measured in calendar days from receipt of an accepted submission to the MDUFA decision and includes both FDA review time and submitter response time ¹.

Put practically, a conventional accepted 510(k) carries a 90 FDA-review-day decision goal and averages roughly 112 to 128 total calendar days to an SE/NSE determination, depending on fiscal year and subject to submission-specific delays such as AI holds ³¹. If FDA misses the 90-day decision goal, it sends a Missed MDUFA Decision communication at 100 FDA days identifying the major outstanding topics and an estimated completion date ³.

Special 510(k) exception. For an accepted Special 510(k), FDA generally completes review within 30 days of receipt. If FDA converts a Special 510(k) to a Traditional 510(k), it becomes subject to the 90-day statutory deadline and the general 510(k) MDUFA performance goals; a Special-to-Traditional conversion during the 15-day acceptance window may itself trigger an RTA because Traditional-content elements are missing ⁷⁷²⁷³.