The Medicare final rule on the payment policy for CTPs/skin substitutes discussed the possibility of creating different pricing structures based on the product’s FDA pathway – particularly for “BLA” products. I didn’t know there were any BLA products approved for wounds – but there are! However, they are only available for specific types of epidermolysis bullosa (EB) or for burns. I asked Dermatologist Dr. Alex Ortega Loayza to explain them, and he’s provided the fascinating article below.
Here’s the background: BLA stands for Biologics License Application. This is the formal FDA submission required for approval to market biological products such as gene and cell therapies. Historically, CTPs/skin substitutes used in routine wound care are marketed either as medical devices or “minimally manipulated human tissues” that are exempt from the FDA process (like amniotics or cadaveric skin). CTP medical devices can come to market one of two ways: a pathway called “Premarket Approval” (like Apligraf and Integra), or via a process called 510 (k). Joe Rolley explained this in a great blog post: What Claims Can Cellular Tissue Product / Skin Substitute Sales Reps Make About Wound Healing? A Closer Look at the Proposed List of 15 in the LCDs.
The BLA products are not drugs, not medical devices, and not minimally manipulated human tissues. All 3 are relatively new. In 30+ years of wound care, I have only seen 2 EB patients, but their suffering has left an indelible impression on me. Although a rare genetic disease, EB patients do sometimes end up in wound centers, so here’s what you need to know about these BLA products thanks to Dr. Loayza.
–Caroline
Dystrophic epidermolysis bullosa (DEB) is an ultra-rare, genetically inherited blistering disorder caused by defects in type VII collagen (COL7A1), the anchoring protein that binds the epidermis to the dermis. Although most patients with DEB have historically been managed in pediatric dermatology and specialized EB centers, two recent FDA approvals—Vyjuvek and Zevaskyn—represent a major scientific turning point that wound care clinicians need to be familiar with. These innovations mark the first time gene- and cell-based biologics have become accessible for a chronic wound condition.
Vyjuvek (B-VEC) is a topical HSV-1–based gene therapy that delivers functional COL7A1 directly into DEB wounds, offering targeted molecular repair rather than symptomatic care. Zevaskyn (pz-cel), in contrast, is an allogeneic cultured keratinocyte–fibroblast therapy that uses living cells to help restore skin structure and function. Both are regulated under the Biologics License Application (BLA) pathway, reflecting their biological complexity, active cellular or genetic components, and the need for long-term safety monitoring—features that distinguish them from traditional wound-care treatments.
For wound-care providers, these approvals signal the beginning of a long-anticipated modernization of wound therapeutics. For decades, innovation in this space was limited, with only a few landmark products such as Regranex (becaplermin, approved in 1997 for diabetic foot ulcers) and early skin substitutes like Apligraf and Dermagraft. More recently, StrataGraft—a viable, bioengineered human skin tissue—was also approved under a BLA for burn wounds, reinforcing the shift toward living-cell and tissue-based biologics. As gene therapy (Vyjuvek) and cell therapy (Zevaskyn) enter routine clinical practice, understanding the distinctions among drug (NDA), device (510k/PMA), and biologic (BLA) pathways becomes increasingly important. These newer technologies introduce additional considerations: specialized storage and handling, new administration workflows, monitoring for systemic or long-term effects, and the need for coordination with dermatology and EB specialty centers. Their arrival in DEB—a rare disease—should be viewed as a positive signal for modernization in wound care, with implications that extend far beyond EB.
What else did we learn from these advances?
- Wound-care centers should prepare for increased patient complexity, new administration logistics, and closer collaboration with pediatric and adult dermatology, geneticists, and EB specialty teams.
- Gene therapy ≠ cell therapy.
These modalities differ in mechanism, durability, handling, safety considerations, and clinical workflow—wound-care providers will need familiarity with both. - BLA-regulated products represent true biological complexity. Vyjuvek, Zevaskyn, and StrataGraft are fundamentally different from older products like Regranex because they involve living cells, genetic material, or tissue functions rather than inert or synthetic mechanisms.
Why the BLA Pathway Matters in Wound Care
BLA-regulated biologics include products derived from living systems or containing active biological components. They require:
- The highest regulatory scrutiny due to complexity and variability
- Long-term safety monitoring
- Stringent GMP manufacturing
- Batch-to-batch potency and functional testing
DEB therapies fall under this pathway because they modify or replace the biological function of skin at a genetic or cellular level, making them fundamentally different from wound drugs (NDA) or devices (510k/PMA).
Alex G Ortega Loayza, MD, MCR
Professor and Interim Chair
Department of Dermatology
Oregon Health and Science University
Dr. Fife is a world renowned wound care physician dedicated to improving patient outcomes through quality driven care. Please visit my blog at CarolineFifeMD.com and my Youtube channel at https://www.youtube.com/c/carolinefifemd/videos
The opinions, comments, and content expressed or implied in my statements are solely my own and do not necessarily reflect the position or views of Intellicure or any of the boards on which I serve.
