The U.S. Food and Drug Administration (FDA) sent an 31 October 2018 Warning Letter to San Diego-based StemGenex Biologic Laboratories LLC (StemGenex) concerning its manufacture and marketing of a human cellular therapy product for autologous use without the necessary prior approval by the Agency.

The FDA conducted an establishment inspection of StemGenex and purportedly found it was processing human adipose tissue (body fat) into stromal vascular fraction (SVF), a human cellular product derived from the adipose tissue. According to the FDA, the product was administered for purposes of treating a variety of serious diseases and life-threatening conditions, including Alzheimer's disease, Crohn's disease, Type I and Type II diabetes, fibromyalgia, spinal cord injury, chronic obstructive pulmonary disease, multiple sclerosis, muscular dystrophy, Parkinson's disease, peripheral neuropathy and rheumatoid arthritis.

The FDA Warning Letter to StemGenex underscores the importance of understanding the Agency's regulatory scheme for human cells, tissues, and cellular and tissue-based products (HCT/Ps). While some HCT/Ps do not require prior marketing approval from the FDA, others do, depending on their characteristics.

HCT/Ps can avoid the need for FDA marketing approval and can be regulated solely under Section 361 of the Public Health Service Act and FDA's implementing regulations at 21 C.F.R. Part 1271 (to prevent the spread of communicable diseases) if they meet all of the following criteria:

  • they are minimally manipulated;
  • they are intended for homologous use only (as reflected by the labeling, advertising, or other indications of the manufacturer's objective intent);
  • their manufacture does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent (provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the product); and
  • Either:
    • they do not have a systemic effect and are not dependent upon the metabolic activity of living cells for their primary function; or
    • they have a systemic effect or are dependent upon the metabolic activity of living cells for their primary function, and:
      • are for autologous use;
      • are for allogeneic use in a first-degree or second-degree blood relative; or
      • are for reproductive use.

21 C.F.R. 1271.10(a).

If a human cellular therapy product does not meet all four of the criteria, it is regulated as a drug and more specifically as a biological product and is subject to all of the requirements that such status entails, 21 C.F.R. 1271.20, including the need for approval by FDA of a biologics license application (BLA) for purposes of marketing. In addition, the product and company also still are subject to certain of the Part 1271 obligations such as the donor eligibility requirements (for non-autologous use) and good tissue practices.

In this particular case, the FDA found that the making of StemGenex's SVF product involves more than minimal manipulation of the adipose tissue. Moreover, the FDA found that the SVF product is not for homologous use. As such, per the Part 1271 regulations, the SVF product is regulated as a drug and more specifically as a biological product, creating the need for approval of a BLA by FDA. StemGenex had no BLA approval for commercial marketing and use of its SVF product.

During the establishment inspection, the FDA purportedly also found evidence of significant deviations from current good manufacturing practice requirements for drugs, 21 C.F.R. Parts 210 and 211, in the manufacture of the SVF product. Purported problems included unvalidated manufacturing processes, an uncontrolled environment, lack of control over the components used in production, and lack of sufficient and validated sterility and endotoxin testing for the product, among other things.

The FDA requested a response from StemGenex, within 15 working days of receipt of the Warning Letter, explaining how the company will correct the deviations cited in the Warning Letter. Deviations not corrected by companies can lead to enforcement actions such as seizure, injunction, or prosecution.

Please let us know if you would like more information or have questions on FDA regulation of HCT/Ps.

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