Understand the Content and Context of FDA Statements
The FDA, to the surprise of nobody, is deliberate in action. There are no smoke signals. No hieroglyphics. Yet some degree of translation is required to grasp the full meaning of their comment and action in December of ‘18 and September of ‘19 regarding the emerging regenerative health industry. The discerning clinician absorbs these messages both in content and context.
The FDA is clear that patient safety is paramount. Quality marches to the beat of the same regulatory drum, just behind patient safety. And both are predicated on current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements. Together these support a dual ethos of guidance provided to the 21st Century Cures Act of 2016: minimal manipulation and homologous use of biologic tissue.
Sections 351 and 361 of the Public Health Service Act (PHSA) provides the authority for FDA to establish regulatory requirements for marketing traditional biologics and human cells, tissues and cellular and tissue-based products (HCT/Ps)
Their, the FDA’s, first action, taken this past December, focused on an organization that thru faulty CGMP fostered a product that directly led to illness. Failing to maintain aseptic environs resulted in a fateful bacteria infection of a biologic tissue product. The public was harmed.
The content of the statement made in the 13th month of this era in the observation of biologic tissue ushered in via the 21st Centuries Cures Act was a stern rebuke of the culprit, Genetech, Inc., who was warned about umbilical cord blood-derived cellular products distributed by Liveyon, LLC.
The context of the message to industry: manufacturing of biologic tissue requires vigilance. This vigilance requires processes that must be both “current” and “good”. The current aspect of the mandate requires processes be relevant & appropriate of this day. The good aspect of the mandate established internal control characteristic of a complete & thorough quality assurance program.
HOMOLOGOUS USE
"to perform the same basic function or functions in the recipient as in the donor"
And this past week’s letter should come as no surprise as to whom the FDA targeted: the manufacturer of a cellular product reliant upon multiple donors.
The content of the FDA declaration to Stemell, Inc was clear and direct: “The FDA’s recent inspection of the Stemell facility in March revealed that the company was manufacturing products derived from human umbilical cord blood and umbilical cord for use in recipients unrelated to the donors of the products. Because these Stemell products are not intended for homologous use only (i.e., to perform the same basic function or functions in the recipient as in the donor) and fail to meet other criteria set forth in applicable FDA regulations,…” and “the FDA documented evidence of significant deviations from CGTP and CGMP requirements in the manufacture of Stemell’s products, including deficient donor eligibility practices, unvalidated manufacturing processes, deficient environmental monitoring and inadequate aseptic processes. These deviations pose a risk that the products may be contaminated with viruses or microorganisms or have other serious product quality defects.”
MINIMAL MANIPULATION
for structural tissue
"processing that does not alter the original relevant characteristics of the tissue relating to the tissue's utility for reconstruction, repair or replacement"
for cells and non-structural tissue
"processing that does not alter the relevant biological characteristics of the cells or tissues"
And the context of the both statements upon the industry is simple. Both statements in December ’18 and September ’19 focused on products reliant upon multiple donors as opposed to a single donor. And both statements involved products that are cellular in nature as opposed to acellular.
The take away here has four dimensions. The take away quadrant:
- seek an acellular biologic product,
- seek an acellular biologic product intended for homologous use originating from a single source donor,
- seek an acellular biologic product intended for homologous use originating from a single source donor adhering to CGTP and CGMP requirements,
- seek an acellular biologic product intended for homologous use originating from a single source donor adhering to CGTP and CGMP requirements and 351/361 compliant
FDA Commissioner, Scott Gottlieb, MD
“Time is running out for firms to come into compliance during our period of enforcement discretion. We’ll be increasing our oversight related to cell-based regenerative medicine as part of our comprehensive plan to promote beneficial innovation while protecting patients.”
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