FDA Registered, Cleared, or Approved? Why the Pathway Matters in Wound Care
By Nikolai Sopko, MD, PhD
President, Chief Scientific Officer & Chief Operating Officer, PolarityBio
In wound care, the word “FDA” associated with a product’s regulatory status evokes trust. However, products may be described as “registered,” “cleared,” “approved,” or “licensed.” The words are often used as if they point to the same kind of review. They do not.
The pathway a product follows determines what the FDA reviewed, what evidence was required, and whether the product was tested for clinical effectiveness before reaching the market.
“FDA” Regulated Can Mean a Lot of Things
Products in wound care reach the market through several different regulatory doors. Those pathways test different things: safety, effectiveness, substantial equivalence, manufacturing controls, or basic tissue-handling requirements.
FDA approval of drugs through a New Drug Application or biologics through a Biologics License Application: This is the highest evidentiary bar for drugs and biologics. A drug that clears this bar is approved; a biologic is licensed, and you will see it described as BLA licensed or BLA approved. For a drug, this requires substantial evidence of effectiveness from adequate and well-controlled studies; a biologic is licensed on a showing that it is safe, pure, and potent, which likewise rests on a demonstration of effectiveness. Either way, review typically includes large confirmatory trials along with safety, manufacturing, labeling, and facilities. This is the pathway to which the terms Phase 1, Phase 2, and Phase 3 belong. Phase 2 studies test early efficacy and dosing in a modest number of patients. Phase 3 studies are the large, controlled, confirmatory trials that form the primary basis for approval.
FDA approval of high-risk devices through premarket approval, or PMA: PMA is a premarket review pathway for devices. It generally requires valid scientific evidence showing reasonable assurance of safety and effectiveness for the device’s intended use.
FDA clearance through the 510(k) route: This is a different and lower bar. It asks whether a device is substantially equivalent to a product already on the market. It does not require a controlled trial demonstrating that the product heals wounds. A cleared product can be perfectly good, but “cleared” is a statement about equivalence, not about proven clinical benefit.
FDA registration as a 361 human cell and tissue product: This is different again, and it is the one most often misread. These products are registered and listed with the FDA. This is a self-designated pathway: the manufacturer itself decides that its product qualifies and registers it with the FDA by completing a simple registration form. They do not undergo premarket review of safety and efficacy. Many skin substitutes sit in this category. “Registered with the FDA” can therefore appear in marketing next to a product that has never been through a controlled trial or an efficacy review.
In short, “FDA registered,” “FDA cleared,” “FDA approved,” and “BLA licensed” describe different levels and types of scrutiny. Biologics are licensed rather than approved, but BLA licensure carries the same evidentiary weight as an approval. Only some pathways require rigorous clinical evidence that the product works for the claimed use. When a claim leans on the FDA’s name, the follow-up should be: through which pathway, and with what evidence?
The Guidelines Themselves Make This Point
None of this is a novel position. Major diabetic foot guidance makes the same point, which matters because clinicians can find it in neutral, authoritative sources rather than in a manufacturer’s materials.
A widely cited American Diabetes Association compendium on diabetic foot complications states that the highest-quality evidence sits with therapies that completed the full FDA approval process, as distinct from those merely cleared by the FDA. The same source cautions that published trials for advanced wound therapies cannot be compared head-to-head, because they differ in design, rigor, inclusion and exclusion criteria, sample size, and follow-up time [1]. The ADA’s more recent compendium on advanced therapies reaches the same conclusion [2].
That warning is practical. Lining up healing percentages from separate studies as if they were equivalent is a common promotional move, but it can be misleading. A 6-week outcome in one small study and a 24-week outcome in a larger, differently designed trial are not interchangeable.
Why This Matters More Now
For much of the last decade, the evidence behind a wound care product and the way it got paid were only loosely connected. That has changed. Beginning January 1, 2026, Medicare reclassified most skin substitutes and moved them to a single flat payment rate of $127.14 per cm², rather than paying each product at its own price [3]. The agency framed the shift as a move away from pricing that had climbed far faster than the evidence behind it [4].
Notably, the reform did not treat every product the same. Products licensed as biologics under Section 351, the BLA pathway, remain on the average sales price methodology, typically ASP + 6%, rather than the flat incident-to supply rate [5]. In other words, the payment system now draws a line that maps closely onto evidence rigor. The pathway that requires controlled trials and full FDA review is treated differently from pathways that do not.
That is the larger point for anyone weighing therapies today. Evidence quality is no longer only a scientific nicety debated at conferences. It increasingly shapes coverage, payment, and access. Clinicians who dig deeper to understand the difference between registration, clearance, approval, and licensure are better positioned for where policy is already and where it appears to be heading.
A Short Checklist for FDA Claims
When a wound care claim invokes the FDA, ask:
Is the product registered, cleared, approved, or licensed?
What pathway did it use: 361 HCT/P, 510(k), PMA, NDA, or BLA?
Did the pathway require clinical evidence of effectiveness for the claimed use?
Were the supporting studies randomized, controlled, and adequately powered?
Is the marketing claim stronger than what the regulatory pathway actually reviewed?
A strong product should be able to answer these questions clearly. If the only evidence offered is the phrase “FDA registered” or “FDA cleared,” the next question should be a review of the level of evidence on the product (see our previous Polarity Perspective that helps evaluate the rigor behind clinical data).
Closing Perspective
Regulatory language is shorthand, and shorthand is easy to stretch. “Registered,” “cleared,” “approved,” and “BLA licensed” each describe a different level of scrutiny, and only some of them required evidence that the product actually heals wounds. That difference has always mattered scientifically. With the CY 2026 payment changes, it now shapes coverage and access as well.
For clinicians, the practical skill is knowing which question to ask when a claim arrives wrapped in the FDA’s name, and recognizing that the answer is usually available in the product’s regulatory status and filings.
Disclaimer — this article is educational and does not describe any specific product. It reflects general principles of evidence appraisal and regulatory interpretation in wound care, based on information published by the FDA and CMS. We encourage anyone reading to do their own research. PolarityBio does not yet have any approved products. SkinTE is currently available for investigational use only.
References
1. Boulton AJM, Armstrong DG, Kirsner RS, et al. Diagnosis and Management of Diabetic Foot Complications. Arlington, VA: American Diabetes Association, 2018. doi:10.2337/db20182-1.
2. Boulton AJM, Armstrong DG, Löndahl M, et al. New Evidence-Based Therapies for Complex Diabetic Foot Wounds. Arlington, VA: American Diabetes Association, 2022. doi:10.2337/db2022-02.
3. CMS, CY 2026 Medicare Physician Fee Schedule Final Rule (CMS-1832-F), reclassifying skin substitutes not licensed under Section 351 as incident-to supplies, effective January 1, 2026, at a payment rate of $127.14 per cm² as set by the CMS correction notice of November 28, 2025. https://www.federalregister.gov/documents/2025/11/28/2025-21458/medicare-and-medicaid-programs-cy-2026-payment-policies-under-the-physician-fee-schedule-and-other
4. CMS, “CMS Modernizes Payment Accuracy, Significantly Cuts Spending Waste,” newsroom press release, October 31, 2025. https://www.cms.gov/newsroom/press-releases/cms-modernizes-payment-accuracy-significantly-cuts-spending-waste
5. CMS, Calendar Year (CY) 2026 Medicare Physician Fee Schedule Final Rule fact sheet (CMS-1832-F), confirming that products licensed under Section 351 of the Public Health Service Act continue to be paid as biologicals under the ASP methodology (typically ASP + 6%). https://www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2026-medicare-physician-fee-schedule-final-rule-cms-1832-f
