An FDA warning letter reveals validation and verification programme for manufacturing equipment is inadequate to prevent cross-contamination
Pharmaceutical giant Mylan has received a lengthy warning letter from the US Food and Drug Administration (FDA) as inspection of its site in Morgantown, West Virginia, revealed quality control flaws and inadequate cleaning and validation procedures deemed significant violations of good manufacturing practices (GMP).
FDA inspectors visited the site between March and April this year. The warning letter, dated 9 November, is the agency's reply to the company's May response to 13 inspectional citations outlined in a Form 483.
Three major areas of concern were outlined in the letter: the cleaning validation and verification programme for manufacturing equipment is inadequate to prevent cross-contamination; investigations into out-of-specification (OOS) test results that didn't consistently identify root causes; and a failure to appropriately manage process changes.
Mylan reacted by issuing a statement on 20 November. The drugmaker said it has implemented a comprehensive restructuring and remediation plan at the Morgantown facility. These activities are already reflected in Mylan's 2018 outlook.
In the statement, Mylan said the issues raised in the warning letter are being addressed within the context of the restructuring plan. "We have been in regular communication with FDA and will continue to work to ensure that the Agency is satisfied with the steps we have taken to resolve all the points raised in the warning letter."
In the warning letter, the FDA cited similar violations across three Mylan facilities and Mylan Laboratories since 2015 and that these repeated failures at multiple sites "demonstrate that Mylan’s management oversight and control over the manufacture of drugs is inadequate".
Previously, a warning letter issued in 2017 to a Mylan facility located in Maharashtra, India, identified a repeat observation made in 2015 regarding unidentified trends in OOS investigations.
This month's missive also said the Morgantown site "failed to establish an adequate quality control unit with the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated".
The agency reported that the site's quality system "does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture."
The FDA acknowledged that Mylan is using a consultant to audit its operation and assist in meeting FDA requirements.
This GMP fail has hit Mylan's reputation and financials; the effect has already been reported in the company's Q3 2018 results. Mylan said the company has "incurred expenses amounting to approximately US$97.7 million and $184.2m for the three and nine months ended September 30, 2018, respectively, for incremental manufacturing variances, site remediation and restructuring charges."
Furthermore, Mylan's financial report showed that total revenues for the period were US$2.86 billion, a decrease of $124.7 million, or 4%, compared to the comparable prior period. Total revenues include both net sales and other revenues from third parties.
"We have an industry-leading track record in global quality management, and we take very seriously our continued and comprehensive oversight of Mylan's entire manufacturing network," Mylan said in a statement. "We continuously learn from inspections of our facilities by FDA and other authorities as regulatory expectations continue to evolve."
Mylan's compliance record has otherwise been fine; the Morgantown warning letter is the only letter from the FDA currently outstanding.
Production of drugs manufactured at the Morgantown facility have been transferred to other sites. Mylan stablished the Morgantown facility 52 years ago and today only eight of Mylan's top 50 gross margin generating products are manufactured at this plant.