Learn the key milestones of FDA’s PMA review – from submission, filing, and mid-cycle feedback to the 180-day goal. Understand possible outcomes (approval, approvable, not approvable, or denial) and how to navigate each stage effectively.
The PMA review process is governed by FDA’s performance goals and regulations that set specific timeframes for certain steps. Understanding these timelines helps you project when you might get to market (and also to respond to FDA promptly when needed). Here’s a breakdown of major timing milestones in the PMA review:
It’s also worth noting that if an Advisory Committee panel is needed, scheduling that meeting can influence timelines. FDA tries to align panel meetings within the 180-day window, but if scheduling or need for additional analyses cause a slip, the timeline can extend. Some PMAs take longer due to complexity or multiple rounds of review. Historically, the average total time to approval (including sponsor delays) might be around 8-12 months or more, but FDA’s review time (their internal clock) is ideally within 180 FDA days.
At the end of the review, FDA will make one of several decisions on the PMA: an approval order, approvable letter, not-approvable letter, or denial. Let’s define each and what it means for you:
This is the outcome you’re aiming for – FDA grants approval for your device to be marketed for the specified indication. It comes in the form of an official Approval Order letter stating that PMA is approved. The approval may list any conditions of approval you must fulfill (such as postmarket study commitments or finalizing labeling). FDA will also publicly announce the approval, often via a Press Release or listing on their website, and will publish a Summary of Safety and Effectiveness Data (SSED) for the device. An approval order means FDA is satisfied that your device is safe and effective and that you’ve met all requirements. You can now market the device, subject to any conditions and post-market obligations. Importantly, an approved PMA effectively licenses your device – but note, if you ever need to make changes, you’ll likely need supplements (more on that in topic 10).
If FDA cannot issue an immediate approval but believes the PMA could be approved with some additional information or actions, they send an approvable letter. This letter will describe specific conditions or deficiencies that must be addressed before approval is granted. Common reasons for approvable letters include: minor labeling changes needed, submission of certain missing test data, or completion of an FDA inspection with satisfactory results. For example, FDA might state that the PMA will be approved once you update the labeling to include a certain warning and FDA verifies your manufacturing facility is compliant. As the applicant, you have a few options: usually, you’ll submit the required information as an amendment to the PMA (or fulfill the condition, like committing to a postmarket study). Once you do and FDA finds it acceptable, they will then issue the Approval Order. Approvable letters delay full approval but signal you’re close. Very rarely, an applicant might treat an approvable letter as a denial and request a hearing, but that’s uncommon. In essence, approvable = “almost there, just do one more thing.”
This outcome is more serious. A not approvable letter means FDA has found significant problems such that the device, as presented, cannot be approved. The letter will outline the major deficiencies in the application. For instance, it might state that the effectiveness was not demonstrated or that safety data are insufficient. It is essentially a rejection of the PMA in its current form, but it stops short of a final denial – you can still salvage the application by addressing the issues. If you receive a not approvable letter, you have to decide how to proceed. Often, it requires gathering new data (maybe a new clinical trial or significant re-analysis) and then amending the PMA or even filing a panel-track supplement later to provide the necessary evidence. While emotionally tough, a not approvable is not the end – it’s FDA’s way of saying “we can’t approve this as is.” You can request a meeting with FDA to discuss the deficiencies and an approach to overcome them. The PMA remains “open” at FDA for some time for you to respond (usually within 180 days for major amendments, although this can be flexible). If after receiving your fixes FDA becomes satisfied, they could convert it to approvable or approval. If you cannot or choose not to fix the issues, you might withdraw the PMA or FDA may proceed to deny it formally.
A denial is a final FDA action where they outright reject the PMA. This typically happens if the deficiencies are egregious or if an applicant fails to adequately respond to a not-approvable situation. FDA will issue an Order denying the PMA, which will list the reasons (e.g., “the device has not been shown to be safe and effective for its intended use”). A denial means you cannot market the device, and the PMA docket is closed. Your recourse then is to either petition for reconsideration/appeal through a hearing process or to start over with a new PMA if you later get new data. Denials are relatively rare, as FDA often works with sponsors through the not-approvable stage to avoid outright denial. However, they do occur, especially if an advisory panel votes overwhelmingly against approval or if time runs out on deficiencies. One important note: if a PMA is denied, that decision is public and the data in the PMA may become available for public disclosure (except confidential info), which could include competitors seeing why it failed. So, companies strive to avoid denial by withdrawing or converting to not-approvable if possible.
It’s worth noting how panel recommendations play into the decision. If a panel recommended against approval, FDA will consider that heavily. But FDA sometimes still approves devices with close or split panel votes by imposing strict conditions or requiring further studies. Conversely, a unanimous positive panel vote can make an approvable or approval more likely, but FDA could still identify issues. Ultimately, FDA (through its Office of Health Technology and Office of Product Evaluation and Quality) makes the call, but panel input is part of the decision process for novel PMAs.
Once FDA makes its decision, it will issue the letter to you via the document control center (and usually email communication as well). If it’s an approval or denial, FDA also publishes a notice (approval announcements online quarterly, and press releases for notable approvals). Approval letters may be accompanied by or followed by a QA meeting to discuss post-market requirements. For example, FDA might want a teleconference to kick off the mandated post-approval study. If you get an approvable or not-approvable, you’ll likely have an interactive discussion with FDA on how to address the issues. The timeline to respond is not fixed in regulations, but generally, companies try to respond within a few months.
Some devices are granted Expedited or Breakthrough Device designation which can affect timelines. Breakthrough Devices don’t change the 180-day statutory clock, but FDA commits to interact more frequently and potentially review portions of the application sooner, aiming to expedite final decisions. Also, under certain programs (priority review), FDA may internally target a shorter timeline. If your device is in an expedited program, you likely had earlier milestones (sprint discussions, etc.), but the final decision outcomes remain the same types of letters, just possibly reached faster.
While the FDA’s timeline has many fixed components, as a sponsor you can do a few things to keep the process moving:
In summary, the 180-day FDA review clock is central to PMA timelines, but real-world total time can vary. Knowing the decision types – and what each implies – prepares you for the possible outcomes at day 180. Whether it’s a joyous approval or a challenging not-approvable, understanding FDA’s perspective and process will help you navigate the next steps effectively. And of course, ADBC CRO’s team will be by your side to accelerate responses and guide you through FDA’s decision process, aiming to turn that approvable into a full approval as efficiently as possible.
