Biologics

Multiple Violations Found at RTI Surgical

David McFarland

— 2 min read
Share

An FDA 4/3-4/28 inspection of RTI Surgical, Alachua, FL, found multiple violations in the firm’s continuing manufacture of a bone graft product consisting of a scaffold composed of human demineralized bone matrix and cortical cancellous chips or strips, copackaged with a redacted isolated bone marrow, cryopreserved in a suspension. An 11/8 Warning Letter says the redacted product is a human cell, tissue, or cellular or tissue-based product that is subject to agency regulation as a drug and biologic product.

The letter says the firm’s product does not have an approved BLA or IND and thus violates the Federal Food, Drug, and Cosmetic Act. The inspection also documented evidence of significant deviation from current good manufacturing practice and the general biological products standards, the letter says. “The deviations in procedures observed as well as those noted in documents collected during the inspection indicate that the use of the [redacted product] raises potential significant safety concerns,” the letter says. “For example, RTI’s unvalidated processes and inadequately controlled environment pose a product contamination risk. Use of contaminated product could cause a range of adverse events, from infections to death. In addition, the high rejection rate of manufactured product demonstrates that your process is not consistent, validated, or in a state of control. This serious lack of control poses a potential significant safety risk for consumers using these products.”

Current good manufacturing practice issues identified during the inspection were: 

  •          failing to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile;
  •          failing 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;
  •          the firm’s aseptic processing areas are deficient regarding the system for monitoring environmental conditions;
  •          failing to establish and document the accuracy, sensitivity, specificity, and reproducibility of test methods used for lot release of the [redacted];
  •          failing to take into account the size and volume of the final product lot during sterility testing;
  •          failing to test the [redacted] for the presence of [redacted] although a reasonable possibility exists that the drug products have been exposed to cross contamination with [redacted];
  •          the system for cleaning and disinfection of the room and equipment to produce aseptic conditions is inadequate;
  •          failing to establish 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;
  •          failing to prepare batch production and production and control records with complete information relating to the production and control of each batch of drug product produced;
  •          failing to conduct routine re-validations of aseptic processes;
  •          failing to validate the manufacturing process for the [redacted] with respect to identity, strength, quality, and purity, as demonstrated in an approximately 62% failure rate for the process;
  •          failing to have adequate environmental monitoring for the presence of microorganisms in the manufacture of the [redacted]; and
  •          failing to have procedures for receipt, identification, storage, handling, sampling, testing, and approval or rejection of specified supplies and components used to manufacture the [redacted]. 

The company was told to take prompt action to correct the deviations and to respond with a list of steps taken to correct the violations and prevent their recurrence, with documentation for each step and a timetable for completion.

Read more