A California-based cell therapy unit that makes human umbilical cord-derived cell and exosome products is facing an FDA warning over several significant quality-related observations.
The FDA warns of “inadequate donor screening procedures, inadequate aseptic procedures, unvalidated manufacturing” and “the risk that your products may be contaminated with microorganisms or have other serious product quality defects.”
Invitrx Therapeutics received a warning letter earlier this month for its Lake Forest, Calif., facility, which was inspected in March and later halted some production.
The letter, which contained 10 main observations, said Invitrx failed to determine and document the eligibility of a cell or tissue donor based on screening and testing results and said it failed to review “relevant medical records” it received from cord tissue suppliers to determine eligibility .
The letter also revealed that since operations began, Invitrx had “failed to determine and document the eligibility of hundreds of tissue donors.” It is reported that tissues from these donors were used to make the products.
The agency also noted that Invitrx failed to verify the aseptic manufacturing process for several of its products, with investigators also observing “primary product containers” for items that are supposed to be sterile stored on a shelf in an “open bag” in the clean room. Caps that are received in bulk have also not undergone further cleaning or sterilization.
Regarding on-site environmental monitoring procedures, the letter stated that Invitrx did not perform environmental monitoring in its aseptic processing area at the time of the inspection, nor did it have written procedures in place.
Two-year expiration dates for some products were established without supporting data, and incubators used for “sterility testing” were also not qualified for this use. Several other quality control issues involving written procedures and additional testing were also noted.
The FDA said “corrective actions” were taken and production of all clinical drug substances and drug product lots at the Lake Forest facility “intended for use in domestic clinical trials” was suspended. However, this is not entirely satisfactory to the FDA.
“It is unclear from this statement whether you have suspended production of all products listed in FDA-483. Furthermore, it is not clear based on your response whether you will be manufacturing your products at any of your other distribution locations. Your answer also describes a “temporary check[s]’ you plan to implement prior to the completion of certain corrective actions, indicating that Invitrx will resume production before adequately addressing existing deficiencies,” the letter said.
It should also be noted that the FDA cannot fully assess the company’s responses to several comments because they do not provide sufficient detail on “corrective actions” and lack a timeline for completing all actions. The response also does not properly address the lack of efficacy of an IND for clinical trials of Invitrx products. However, Invitrx has committed to recalling distributed products.
Invitrx has been invited to a “regulatory meeting” with the FDA to discuss the steps that have been taken since the March inspection. The meeting is scheduled for mid-December.
Endpoint news has reached out to Invitrx for comment on the letter, but has not received a response by press time.