Zimmer Biomet’s medical device manufacturing facility in Indiana drew a Form 483 from the US Food and Drug Administration (FDA) after an April site inspection revealed issues dating back to 2016 that remain unresolved—many of which were linked to inadequate procedures for corrective and preventive actions (CAPAs).
Out of the 11 inspection observations noted in the 483, eight were initially cited following an FDA visit conducted in 2016. The site reinspection—conducted between 9 to 24 April—concluded these eight observations have yet to be addressed to the extent needed.
As part of the repeat observations, most the of issues relate to the firm’s CAPA procedures, with FDA investigators pointing to a range of recently opened investigations to explain how they were deemed inadequate. For example, the investigators found “corrective actions were not effective in preventing reoccurrence of bacterial endotoxin test failures in polyethylene devices.”
Several CAPA investigations were initiated to address the test failures and determine whether field actions were necessary between 2016 and 2017.
Yet the study report Zimmer Biomet had used to justify not taking additional actions—other than the 2016-2017 recall of certain polyethylene product—had some flaws as it could not be used to demonstrate the firm’s manual cleaning process for operators could be performed consistently across different worst-case scenarios. FDA previously flagged this process validation as inadequate.
Another CAPA in 2016 had been opened to assess the need for remediation of design history files (DHF) over design control issues. The firm conducted device performance reviews for its DHFs, but it failed to take “a plenary ‘risk based’ approach to evaluating products that have been and are still being distributed” since its evaluation only involved “one subset of complaints/MDRs (revision surgery)," according to FDA.
Other repeat observations include improper validation of a sterilization cycle, failure to ensure suppliers use adequate test methods, no documented rationale in support of product acceptance criteria, as well as inadequate procedures to monitor process parameters and safeguard process controls.
Inefficiencies in the firm’s procedures for conducting risk analysis and ensuring routine calibration and maintenance of equipment were among the observations newly noted in the latest 483. A lack of policies for employee training was observed for the first time by FDA as well.
In response to the 483, Zimmer Biomet issued a statement on plans to “execute against its approximately two-year quality remediation plan at the Warsaw North Campus.”
The firm argued that “none of the observations identified a specific issue regarding the performance of any particular product and all products continue to be manufactured by the facility.”
FDA Form 483