FDA Issues Warning Letter to American CryoStem

January 5, 2018

FDA noted in a recent inspection that American CryoStem was receiving and processing adipose tissue into a product called Atcell, and then marketing the product without agency approval.

FDA sent a warning letter, dated Jan. 3, 2018, to American CryoStem and its Chairman/CEO, John S. Arnone, for marketing an adipose-derived stem cell product without agency approval and for significant deviations from current good manufacturing practice (CGMP) requirements, including some that raise potential significant safety concerns and put patients at risk.

FDA inspected American CryoStem’s Monmouth Junction, NJ facility from July 17 to July 26, 2017 and found that the company was receiving and processing adipose tissue (body fat) into a product called Atcell, and then marketing the product without the required agency approval. Though the product is intended for use in the same individual from which it was recovered, the manner in which it is being processed involves more than minimal manipulation of the adipose tissue. These manufacturing steps alter the original relevant characteristics of the tissue and have the potential to introduce contamination of the product, creating risk of harm to patients. Under existing law, the product is required to undergo FDA review to ensure the treatment is safe and effective.

During the inspection, FDA found evidence of significant deviations from CGMP in the manufacture of Atcell that pose significant additional risks, such as potentially being contaminated with microorganisms or having other serious product quality defects. According to the agency, specific deviations included unvalidated processes, an inadequately controlled environment, lack of control of components used in production, and a lack of sufficient and validated product testing.

“The use of Atcell raises potential significant safety concerns, due in part to the fact that there is little basis on which to predict how the product will perform in a patient,” said Peter Marks, MD, PhD, director of FDA’s Center for Biologics Evaluation and Research. “In addition, this product may also cause harm to patients who may put their trust in an unproven therapy and make the decision to delay or discontinue medical treatments proven to be safe and effective.”

Subsequently, American CryoStem was issued a list of inspectional observations at the conclusion of the inspection. The firm has responded to those observations; however, FDA has found that the response does not fully addresses the observations and fails to recognize that a valid biologics license must be in effect to lawfully market Atcell. While in the development stage, an investigational new drug application must be in effect to lawfully distribute Atcell for clinical use. FDA has requested a response from American CryoStem within 15 days that details how the violations noted in the warning letter will be corrected.

“As part of our comprehensive policy framework for the efficient development and regulation of cell-based regenerative medicine, we’re going to be stepping up enforcement activities against those who manufacture and market products in ways that put patients at risk,” said FDA Commissioner Scott Gottlieb, MD, in an agency press release. “We see great promise from the field of cell-based regenerative medicine, but there are also novel risks. Our goal is to implement our new policy framework in a way that helps this promising field advance, while making sure that we address issues that can put patients at risk. It also means taking an efficient, risk-based approach to making sure that products undergoing more than minimal manipulation, which makes them subject to FDA’s review and approval, and particularly products intended to treat serious and/or life-threatening disease or conditions, must prove that they deliver the benefits they’re promising to patients.”

Source: FDA and FDA Warning Letter