Bayer In FDA's Bad Books Over Facility Failures
Executive Summary
Not for the first time this decade, the German major has been warned by the US FDA about its manufacturing processes and sorting out the problems could affect supplies of some big-selling products such as the blood pressure treatment Adalat and the erectile dysfunction drug Levitra.
Bayer AG has fallen foul of the US Food and Drug Administration's inspection teams and the agency has issued a lengthy warning letter about significant manufacturing violations at the German group's Leverkusen facility that ultimately could affect future approvals.
The FDA has published the warning letter sent in November which relates to an inspection of the Leverkusen plant in January last year and has made it very clear that it is less than impressed with Bayer's response to tackle the problem. Stating that "your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to current good manufacturing practice (CGMP)," the list of violations is a long one.
Bayer stands accused of failing to establish and follow adequate written procedures for cleaning and maintenance of equipment, and not thoroughly investigating "any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed." Among the other charges is that Bayer's quality control unit did not sufficiently oversee adequacy of procedures at the facility to assure drug product quality.
The FDA team observed discarded original personnel training records and found forms used to document and set inspection parameters for automated tablet visual inspection machinery – which are used to accept or reject tablets – in a waste bin. The agency also stated that Bayer failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards.
The letter went on to say that Bayer's responses to the issues raised have been inadequate and action plans submitted by the company in May and August last year fall short of the agency's demands. It wants to see revised action plans and the letter stated: "Until you correct all violations completely and we confirm your compliance with cGMP, the FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer."
The agency noted that "failure to correct these violations may also result in the FDA refusing admission of articles" manufactured at the Leverkusen site into the US. It concluded by asking Bayer to make contact "if you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility" and demanding a response to the letter within 15 working days, specifying "what you have done since our inspection to correct your violations and to prevent their recurrence."
In response, Bayer sent a statement to Scrip saying that since the initial routine inspection in January 2017, the company had "continued to implement remediation activities in a timely manner [and] relevant regulatory authorities have been kept informed." Bayer added that it was "fully committed to diligently addressing the FDA observations and to continue the corresponding implementation of necessary corrective actions. Comprehensive reports on the progress of these corrective actions have been shared with the agency."
The company went on to say that it had "no evidence that patient safety was or is at risk" and release and distribution of products from Leverkusen continues. However, "due to the ongoing remediation and also modernization measures at the site, we expect temporary supply limitations affecting our mature product portfolio."
A company spokesman told Scrip that the products affected include some big-earners, such as the blood pressure treatment Adalat (nifedipine) and the erectile dysfunction drug Levitra (vardenafil). Bayer added that "the business impact will be reflected in our upcoming 2018 guidance," to be issued when the company hosts its annual results in Leverkusen Feb. 28.
As to the effect of the FDA warning on Bayer's fortunes, PharmaVitae company analyst Oliver Spray told Scrip, "It is clearly important as Leverkusen is its main manufacturing site in Europe." He added that whether it will have any major material effect on revenue and regulatory submissions going forward will depends to how the company responds to the letter and whether it results in a significant upheaval in manufacturing processes.
However, "given its dampened response to these warnings in the past, Bayer is likely to prioritize maintaining sales of its drugs," Spray said. The company was previously hit by a warning letter from the FDA over its manufacturing in Germany. One was issued in 2009 following an inspection of the firm's non-sterile active pharmaceutical ingredient manufacturing facility in Bergkamen, where Bayer was again criticized for not adequately addressing deficiencies. (Also see "US warns Bayer API facility in Germany over GMP violations" - Scrip, 16 Sep, 2009.)
Thank you for reading this article. To improve the content and delivery of our products, we would love to speak with you about your role and content needs. Sign up here, and we will contact you to set up a 30-minute chat. As a gesture of appreciation, you can select one of 10 Pharma Intelligence special reports (valued up to $7,500) that we will send you FREE of charge.