番茄社区

The FDA is again clamping down on unapproved stem cell therapies, this time with a expressing safety and regulatory compliance concerns involving umbilical cord cellular products marketed by of Pensacola, Florida.

The FDA said the company's products are unapproved drugs marketed to physicians and medical clinics for an unapproved use, and that processing procedures do not meet safety requirements.

The products in question -- referred to as "Wharton's Jelly," a substance that insulates the umbilical cord in the womb -- include brand names ProText, CoreText, CryoText Pro, CryoText Plus, SecreText, and SecreText Pro.

A key issue in the FDA's letter is that the products are not used in homologous ways that umbilical cord cells normally serve. "Using your products to treat orthopedic diseases or conditions, for example, is not homologous use...," FDA wrote.

Nor do the products meet minimal manipulation criteria, as processing "alters the original relevant characteristics of the umbilical cord," the letter states.

Thus, the product does not meet standards to be considered a "361" human tissue product, and should be classified as a "351" biologic drug, requiring more substantial regulation, the agency said.

FDA also raised concerns about "significant deviations from current good manufacturing practice (CGMP) requirements." That includes the fact that its aseptic practices "have not been validated" and that personnel practices "do not adequately protect against microbiological contamination of your products."

For instance, operators were observed processing one of the products "without changing or disinfecting the outer pair of sterile gloves donned in the ISO 8 hallway," the letter stated.

They also were observed "repeatedly passing gloved hands and sleeves over containers of open, in-process umbilical cord tissue within the BSC [biological safety cabinet] as well as using gloved hands as a seal to cover open containers of in-process umbilical cord tissue during processing."

"Failure to adequately address these matters may lead to regulatory action without further notice," Michael W. Roosevelt, program division director of the FDA's Office of Biological Products Operations, wrote in the warning letter. "Such actions include seizure and/or injunction."

The June 21 letter was addressed to Tyler C. Barrett, President and CEO of Row1 Inc., dba Regenative Labs.

Barrett sent 番茄社区 a three-page , addressed to healthcare providers, insisting that Regenative is compliant with all regulations and that its products are safe.

He said that "within the umbilical cord, Wharton's jelly serves the important basic function of providing structural support and cushioning against compressive forces from the surrounding environment. While the anatomical location may differ, that basic function remains the same."

Barrett continued, "regardless of anatomical location, structural cushioning and support is the basic function intended to be served by Regenative's Wharton's jelly HCT/Ps," human cellular and tissue-based products.

The FDA apparently disagrees. Its letter stated that the products contain human cells, tissues, or cellular or tissue-based products and are subject to regulation and premarket review, which was not obtained. Nor does Regenative have an investigational new drug (IND) application open for any of its products, FDA said.

The warning letter to Regenative Labs is the latest in a series in which the FDA found problems with companies marketing umbilical cord stem cells and so-called "birth tissue" for other purposes, such as orthopedic diseases or conditions.

Additionally, Medicare, which has paid for some of these applications, apparently has pushed back as well, clawing back reimbursements paid to clinicians who submitted claims for injecting products that did not meet 361 requirements and were not approved drugs.

In his last week, Regenexx's Chris Centeno, MD, referenced six other companies that got in trouble with the FDA for pushing Wharton's jelly products.

"The angle for Regenative was also unique," he wrote. "On the billing side, the company focused on 'filling a tissue defect.' This was very creative as Medicare approves countless products for this purpose. The only problem was that Medicare never authorized the use of umbilical cord tissue for this application."

Zubin Master, PhD, a biomedical ethics expert in regenerative medicine at the Mayo Clinic in Rochester, Minnesota, who emphasized that he was not speaking on behalf of Mayo, agreed that the FDA is cracking down, and that it should.

Reading the FDA's warning letter, Master said he saw a "plethora of concerns," similar to those conveyed to "other clinics and businesses practicing in this space. The sterility aspect is a kind of potential harm, but there are all kinds of other harms as well, for example, a person who may be very desperate, who is suffering from something untreatable. They may wind up paying a lot of money for a product that's completely unproven and may not do anything."

In guidance issued several years ago, he said, the FDA made it clear that any kind of biological product sold for non-homologous use would have to file a biologics license application and go through clinical trials.

He gave as an example of a company that uses human fat cells in an area of the brain to treat a neurological disorder like Parkinson's. "Now, you're not using it for the same purpose."

Comment