One Product's Regulatory Pathway Explained: 351 Biologic and Reimbursement Impact

In this interview, Nikolai Sopko, MD, PhD, and Ned Swanson, MD, break down the FDA’s 351 regulatory pathway and explain how one product's transition from a 361 HCT-P to a full Biologics License Application (BLA) distinguishes it from others. Their insights highlight the evolving regulatory landscape shaping wound care innovation, Medicare policy, and future reimbursement.

Key Takeaways:

• The discussed product's regulatory shift from 361 to 351 positions it as a true biologic drug, requiring full FDA pre-market approval, clinical trials, and a Biologics License Application—far more rigorous than traditional tissue-based products.

• There are tightening definitions and oversight of 361 HCT-P products, prompting companies with more complex technologies to pursue the 351 pathway to ensure safety, efficacy, and long-term market stability.

• This regulatory distinction will significantly shape future reimbursement, as Medicare and commercial payers increasingly use FDA pathway designations to differentiate policies for biologics versus conventional skin substitutes or CTPs.

Please note: This content is a direct transcript, capturing the authentic conversation without edits. Some language may reflect the flow of live discussion rather than polished text. 

Nikolai Sopko, MD, PhD:

I could start off with just a quick overview of 351, I think is always helpful, because as you said, it's not as common of a pathway, especially in the wounds. That's the specific code regulated for biologics by the FDA. And so you have two large kinds of drug classes, which is your small molecule process, and then your BLA process, which is regulated by the 351. Biologics as a class is sort of interesting because it can be either a 351 or a 361, which is your human cell tissue product pathway, the HCT-P pathway. And so, those can both sort of be referred to as biologics.

But, when you think of a biologic drug, that's the 351 regulatory pathway that the FDA has identified. And that essentially has the same regulatory pathway as a small molecule as a drug, where you have to get full pre-market approval through the FDA, kind of walking through your phases of your clinical trials, and then submitting a very large application at the end of that, which we're actually in preparation of doing, and then going through the full approval process to get approval by the FDA with the 351. And that was something initially we had launched as a 361 product back in 2017. And then we're actually on the market for several years, treated upwards of 1,300 patients. And then through that time, we're working with the FDA. They were doing some updates to their 361 language and ending their discretion period, and we voluntarily reached out to the FDA knowing that our product was quite unique and through a process called a pre-request for designation, where we went to Silver Spring, presented to them, went in front of them all voluntarily and said, hey, this is our product, where do you think we would best fit? And that's when they responded, we think you'd be better served by the BLA 351 pathway.

The 361 pathway is a self-designation pathway. That pathway was really designed with the intent for tissue, tissue banks, tissue products, when we think about bone allografts, things like cadaveric skin, those are often regulated on the 361 pathway. So, it was meant to be a relatively low burdensome pathway to get products pretty quickly to the market. But as your product increases complexity, that's when they can say you're better served by a 351 pathway to make sure that you are safe and effective. And so through that process, we worked with the FDA and then voluntarily took our product off the market and then submitted our IND in May of 2021 and then had our IND open in 2022 and it has been going through the clinical trial process since then.

Ned Swanson, MD:

I think when you take that regulatory background from that lens, it far separates an autologous heterogeneous skin construct (SkinTE) from what is traditionally termed a CTP, a skin substitute, a CAMP, whatever terminology you want to use in terms of that. And then, you know, how that will affect things going forward, on the Medicare side and on the payer side, they're starting to put into place regulatory pathway designations to designations to determine their different policies.