FDA Warns Integra’s TEI Biosciences Over Contamination Issues

A TEI Biosciences medical device facility drew an US Food and Drug Administration (FDA) warning letter earlier this month over failures to prevent bacterial contamination of certain manufacturing equipment and products.

The warning letter, made public on Tuesday, cites four good manufacturing practice (GMP) violations for the manufacturer of collagen-based medical devices. The first three GMP violations cover a lack of procedures to control environmental conditions as well as insufficient bacterial endotoxin testing data. The firm’s Xenform Soft Tissue Repair Matrix is at issue in all three.

The Integra LifeSciences firm manufactures devices for wound care, soft tissue repair and reconstruction surgery, but lacked adequate validation of processes used to manufacture the FDA-cleared Xenform Soft Tissue Repair Matrix at the time of the October and November 2018 inspection of its facility in Boston.

“We take the matters identified in the letter seriously and are in the process of preparing a written response to the letter,” Integra said in an SEC filing earlier this month. “The company has provided detailed responses to FDA as to its corrective actions on a monthly basis and, since the conclusion of the inspection, has undertaken significant efforts to remediate the observations and continues to do so.”

The plant lacked data to demonstrate bacterial endotoxin testing of its extracellular bovine matrix medical devices (EBM) had been adequately validated and that a water system used to manufacture EBM devices included bacterial endotoxin testing, according to the warning letter. TEI Biosciences “was not routinely performing microbial identifications on the bioburden recovered from the firm’s…water system,” said Joseph Matrisciano, program division director at FDA’s Office of Medical Device and Radiological Health. These deficiencies “demonstrate a systemic failure” of quality systems.

Further, a sporicidal disinfectant had not been used in the firm’s ISO 7 clean rooms since March 2017 at the time of FDA’s visit. “We are aware that your firm identified spore-forming bacteria and fungal organisms (such as Bacillus thuringiensis and Cladosporium halotoerans), during routine Xenform Soft Tissue Repair Matrix bioburden testing,” Matrisciano said. The warning letter points to several observed deficiencies regarding the firm’s procedures to adequately control environmental conditions, such as the lack of details in the firm’s procedure for cleaning its clean rooms to prevent cross contamination.

For each of the first three violations, FDA will conduct a re-inspection of the TEI Biosciences facility to verify that all corrective actions promised to address the issues have been appropriately implemented.

The remaining GMP violation relates to the observed failures around corrective and preventive actions (CAPAs). The firm, for example, opened a CAPA in August 2017 to address 19 nonconforming material reports about tears on certain pouches during the lyophilization process. It then closed this CAPA last March despite identifying six additional tears during the investigation, according to the warning letter. 

Warning letter