End of FDA “grace period” impacted perinatal cell therapy biotechs

If there’s one area of biologics where the FDA has been consistently busy lately it’s the perinatal cell therapy space.

The agency has made it clear in the last year that allogeneic birth-related cell products are often drugs requiring premarket approval. This has mainly manifested at a practical enforcement level. We’ve seen actions taken in regard to unproven, birth-related stem cell and cell therapy clinics and their suppliers.

Previously I discussed the pattern I saw with the  FDA letters sent to such clinic-related firms. However, I got a heads up that more recently the agency’s oversight policies in this perinatal cell therapy space have also affected quite a few biotech companies.

FDA cell therapy ‘grace period’ ended

The link in the previous sentence is to a helpful article in Great Practice that focuses on amniotic products that have been pulled from the market by the end of the FDA’s discretionary enforcement period in the cell therapy space.

Below I outline some examples of firms that cited the end of the FDA enforcement discretion period in SEC filings as a reason to pull their products. These examples are different from those cited by Great Practice.

It seems that such products are classified as drugs requiring full FDA approval under the newer guidelines. Another interesting element to this is that these products were already on the market before, perhaps reflecting past ambiguity on the status of such products as 351 or 361. As of about a year ago, the FDA clarified that a wide range of perinatal products are 351s.

Perinatal biologic therapies pulled by specific biotechs

Axogen

“Effective June 1, 2021, we voluntarily suspended the market availability of Avive Soft Tissue Membrane. The decision to suspend market availability of Avive was made following a communication with the FDA on May 14, 2021 regarding the appropriate classification and regulatory approval requirements for Avive. The suspension of market availability was not based on any patient safety or product performance issues or concerns associated with Avive Soft Tissue Membrane, a product that had been marketed by Axogen and routinely used by surgeons for patient care since 2016. Avive is a processed human umbilical cord intended for surgical use as a resorbable soft tissue barrier…We will continue discussions with the FDA with the goal of returning Avive to the market. There is no guarantee, however, that we will return Avive to the market.”

Bioventus

“We began selling MOTYS in the cash pay market during the fourth quarter of 2020 as human cells, tissues and cellular and tissue-based product (HCT/P) pursuant to a temporary FDA policy of enforcement discretion. Following the end of this temporary enforcement discretion policy on May 31, 2021, we were required to cease selling MOTYS and will not be able to resume sales of MOTYS in the United States unless and until such time as we obtain approval of a Biologics License Application (BLA).”

Integra

“The HCT/P Final Guidance maintains the FDA’s position that products such as the Company’s morselized amniotic membrane tissue-based products do not meet the criteria for regulation solely as HCT/Ps. In addition, in the November 2017 guidance, the FDA articulated a risk-based approach to enforcement and, while some uses for amniotic membrane tissue-based products would have as much as thirty-six months of enforcement discretion, other high risk uses could be subject to immediate enforcement action. The 2020 HCT/P Final Guidance maintained this approach and extended the discretionary enforcement period to May 31, 2021. Considering the risk of enforcement action, the Company discontinued the manufacturing of all morselized amniotic membrane tissue-based products prior to May 31, 2021. We no longer distribute these products. As of December 31, 2021, the Company has not received any further notice of enforcement action from the FDA regarding its morselized amniotic membrane tissue-based products.”

Mimedx

“The Company ceased marketing and selling AMNIOFILL in the United States in May 2021, following the end of the FDA’s period of enforcement discretion. We have not yet initiated any clinical trials in furtherance of any regulatory approvals for this product.”

Organogensis

“On April 21, 2021, the FDA reaffirmed that the enforcement grace period would end on May 31, 2021, at which time we ceased commercial distribution of ReNu and NuCel. Although we believe our suspension of ReNu and NuCel commercialization was timely and proper, the FDA and other regulators may disagree with how or when such commercialization practices were conducted, which could expose us to regulatory sanctions, and have a material adverse effect on our business, financial condition and results of operations.”

Some cell therapy perspectives

The pulling of these products by biotechs because of the end of the discretionary period is notable. It also contrasts sharply with the lack of compliance by unproven stem cell clinics and suppliers during the same period. What we’re hearing (and just kind of directly seeing) with the stem cell clinics isn’t encouraging. Most failed to make changes toward compliance during the discretionary period.

Perhaps the 3+-year “grace period” was more about the FDA giving time to good citizen biotechs.