FDA warns five device makers for Quality System, CAPA issues

The US Food and Drug Administration (FDA) has warned five medtech companies for failing to meet current good manufacturing practices (CGMP) requirements under the Quality System (QS) regulations. The most common concern raised by inspectors is their failure to meet expectations for corrective and preventive action (CAPA) plans.

On 14 January, FDA published five warning letters issued in December to Hologic, Integra Lifesciences, Randox Laboratories, Xoran Technologies, and Phillips Precision, detailing deficiencies found at the companies’ manufacturing facilities. The letters address concerns about failing to meet device control procedures, device validation, acceptance procedures, and CAPA requirements.

In a 19 December letter, FDA inspectors said Hologic, “[Failed ]to establish and maintain procedures for implementing corrective and preventive actions, including requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems using appropriate statistical methodology.”

While the manufacturer had already pulled the products from the market and responded to a Form 483 regarding the deficiencies with steps it was taking to address the FDA’s concerns, inspectors said Hologic's actions were insufficient. The agency said its response did not accurately calculate the occurrence rates of adverse events associated with its BioZorb implantable radiographic markers because it does not properly account for the intended patient population and it was concerned about the lack of follow-up design studies to determine how the product affects patients already implanted with the devices. (RELATED: Hologic warned over recalled BioZorb implants, Regulatory Focus 14 January 2025)

Similarly, FDA inspectors said that Integra also failed to follow CAPA requirements at some of its facilities, and the results from its CAPA implementations other facilities can’t be evaluated until November 2025.

“A review of quality data sources over individual Integra sites, including corrective and preventive actions (CAPAs) and quality plans (QPs) taken at numerous Integra firm locations revealed that site specific CAPAs are not evaluated for escalation to corporate wide CAPAs,” the agency added.

As an example, FDA noted that a CAPA was initiated on 7 April 2023 due to findings from endotoxin testing at one of its facilities, but the company failed to provide justification and documentation for its decision to not escalate the CAPA to the rest of the company.

The complaints against Integra are reminiscent of a warning letter issued to the company in 2023. Integra was cited for releasing collagen-based products that failed bacterial endotoxin testing in that letter. The company was also cited for other violations of good manufacturing practices (GMPs) associated with its products, which are intended for wound care, soft tissue repair, and reconstructive surgery. (RELATED: FDA warns Integra LifeSciences over endotoxin testing, complaint investigations, Regulatory Focus 12 August 2023)

In the latest warning letter, Integra was also cited for failing to review and evaluate process changes and deviations and perform revalidation when changes or process deviations happen. FDA inspectors cited several instances where the company failed to address the issue with process changes, including an instance at its Mansfield, MA, facility where the company failed to assess the impact of annual sterilization requalification parameter failures for ethylene oxide (EO) cycle that assures they can sterilize products reliably.

"On December 2, 2020, a deviation occurred with eight temperature sensors recording temperatures below the minimum [required] degrees Fahrenheit for the product temperature during the EO exposure dwell phase, failing to meet the predetermined validation acceptance criteria," said FDA. "Your firm failed to investigate the cause of the temperature failure and the potential effect on the EO cycle for routine sterilization."

Another recurring issue raised in the warning letters is the failure of some manufacturers to establish and maintain adequate device design validation procedures, which includes conducting proper risk analysis. For instance, FDA investigators said that Randox Laboratories had initiated five Class II recalls over the past seven years related to instances where assay reagents carried over to subsequent tests from previous tests, leading to erroneous diagnostic results. While the company has tried to address the issue, the agency said the company’s risk management plan was inadequate.

"Your firm has identified that the root cause is related to ambiguity in your risk analysis procedures, lack of clear responsibility for the activities, and that maintenance of the risk management files and not been effective," said FDA. "Your firm states that you have reviewed and updated the risk management files for the recalled products, however, copies of those files were not provided for review because they are currently under review by specified teams at your firm. An estimated date of completion was not provided."

FDA noted a similar issue in its letter to Xoran Technologies but acknowledged that the company had opened a CAPA in response to determine why its risk analysis was inadequate to address risks associated with its products and planned to add the probability of occurrence to its harms analysis. However, the agency noted it could not determine the adequacy of the manufacturer's steps.

All the companies that received warning letters from FDA were given 15 days to respond to the agency’s concerns. Inspectors asked the companies to outline the steps they plan to take to address FDA’s concerns and a timeline detailing how they plan to implement those steps.

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FDA warns five device makers for Quality System, CAPA issues

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