Biologics

Multiple Violations at Invitrx Therapeutics

David McFarland

— 2 min read
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A 3/1-3/22 FDA inspection at Invitrx Therapeutics, Lake Forest, CA, found multiple violations in the firm’s manufacturing of cellular and acellular products for allogeneic use. An 11/9 Warning Letter says the products are intended to be administered by injection, ophthalmically, or by nebulization and purport to be sterile.

The letter says the products are defined as drugs and biological products and are illegally marketed without an approved BLA or IND, neither of which the company has.

FDA says the inspectors also documented evidence of significant deviations from current good manufacturing practice (CGMP) and current good tissue practice (CGTP) requirements. “The deviations in manufacturing observed, as well as those noted in documents collected during the inspection, indicate that the use of your products raises potential significant safety concerns,” FDA says. “For example, your deficient donor screening practices, inadequate aseptic practices, unvalidated manufacturing processes, and deficient environmental monitoring … pose a significant risk that your products may be contaminated with microorganisms or have other serious product quality defects.”

The letter lists these significant CGMP and CGTP deviations:

  • failure of a responsible party 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 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 satisfy general biological products standards for sterility testing;
  • failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess;
  • 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 withhold from use each lot of components, drug product containers, and closures until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit;
  • failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use the results of such stability testing to determine the appropriate storage conditions and expiration dates;
  • failure to follow written procedures describing the handling of all written and oral complaints regarding drug products;
  • failure to prepare batch production and control records for each batch of drug product produced that include complete information relating to the production and control of each batch, including documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished; and
  • equipment used in the manufacture, processing, packing, or holding of drug products is not of appropriate design to facilitate operations for its intended use.

The letter says Invitrx’ response to the form FDA-483 observations was inadequate. The company was told to respond with a list of specific steps it has taken or plans to take to address any violations and prevent their recurrence, with the necessary documentation and a schedule for completing the corrections. It also was asked to participate in a regulatory meeting to discuss the status of its corrective actions.

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