FDA Warns Umbilical Cord Blood Firm

A 3/4-3/8 FDA inspection at Stemell, Inc., San Juan Capistrano, CA, found current good manufacturing practice (CGMP) and current good tissue practice (CGTP) violations in the firm’s manufacturing of products derived from human umbilical cord blood and umbilical cord for allogenic use. An 8/28 Warning Letter says the firm describes itself as “specializing in the harvesting and isolation of stem cells to manufacture and commercialize innovative products” and says the products are distributed directly to doctors throughout the U.S.

The letter says the firm’s products are defined as drugs and biological products under the applicable laws. The products are also human cells, tissues, or cellular or tissue-based products (HCT/P) as defined in the law and subject to regulation, it says. FDA says the products fail to meet the criterion that HCT/P be intended for homologous use as shown in the labeling, advertising, or other indications of a manufacturer’s objective intent.

The company was informed in the letter that since it does not meet the HCT/P criterion and does not qualify for an exception, its products are regulated as drugs and require a valid BLA or IND, Since neither of those are in effect, FDA says, the company is in violation of the Federal Food, Drug, and Cosmetic Act.

During the inspection, the letter says, FDA documented evidence of significant deviations from CGMP and CGTP. “The deviations in manufacturing processes observed as well as those noted in documents collected during the inspection indicate that the use of your products raises potential significant safety concerns,” the agency says.

The letter says the deficiencies were: 

•          failure of a responsible person to determine and document the eligibility of a cell or tissue donor based on the results of donor screening and donor testing;
•          failure to establish and maintain procedures for all steps performed in testing, screening, and determining donor eligibility, and complying with all other requirements in regulations;
•          failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes;
•        failure to have separate or defined areas or such other control systems as necessary to prevent contamination or mixups during the course of aseptic processing including, as appropriate, a system for monitoring environmental conditions and a system for cleaning and disinfecting the room and equipment to produce aseptic conditions;
•          failure to establish written procedures for production and process control designed to assure drug products have the identity, strength, quality, and purity they purport or are represented to possess;
•          failure to establish and follow written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures;
•          failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity;
•          failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates;
•          failure to perform routine calibration, inspection, or checking of electronic equipment according to a written program designed to assure proper performance, and to maintain written records of such calibration checks and inspections;
•          failure to establish and follow written procedures describing the handling of all written and oral complaints about a drug product; and
•          failure to establish a quality control unit that has the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated.

FDA acknowledges the firm’s responses to the inspection observations and its corrective actions. “However,” the letter says, “based on the information you provided for review, we have concerns regarding the adequacy of your corrective actions to date including, but not limited to, those pertaining to donor eligibility determinations, aseptic process validation, validation of the manufacturing processes, your stability program, cleanroom qualification, and the responsibilities of your quality unit. Notably, your responses do not address your firm’s immediate plans regarding the continued manufacture of your products, given the significant deficiencies identified, or the potential serious risks to patients your manufacturing violations present.”

The agency also says the firm’s responses did not address its failure to have an IND or BLA in effect. And it says the firm’s Web site uses the FDA logo, which is not allowed to be used on private sector materials.

Stemell was told to take prompt action to correct the violations and to respond with a list of specific steps taken to correct the violations and prevent their recurrence, with documentation of each step and a schedule for completion.

FDA also issued a news release detailing the Stemell violations and agency actions on HCT/P innovation and regulation.