India’s Badrivishal and China’s Lumis are the latest to be under the spotlight.
The U.S. Food & Drug Administration (FDA) sent two more warning letters to API manufacturers in March, one in India and one in China, following inspections at their sites last year. This brings the total number of warning letters this year to 14. It all follows a pattern of increasing stringency that saw 42 warning letters issued in 2016.
Badrivishal Chemicals & Pharmaceuticals received its warning letter following an inspection at its facility at Talegaon in India’s Maharashtra province last August that established multiple significant deviations from current Good Manufacturing Practice (cGMP) in API production. A subsequent response was deemed inadequate on most points because it failed to specify what corrective actions would be taken.
In particular, the inspectors noted a failure to validate and monitor the water purification system. The company had failed to test source water, which comes from a river and passes through nearby farmland, and to store it in a way that protected it from pests and contaminants. In addition, the sanitization of the water was deemed inadequate; the FDA questioned whether the company even understood the process used by the water system to destroy microorganisms.
Badrivishal was also taken to task for the failure of its quality unit to prepare, review and approve documents related to the manufacturing of API, failure to verify the suitability of analytical methods carried out by an outsourced supplier and failure to investigate critical deviations impurity testing chromatograms that contained unexplained discrepancies.
Meanwhile, Lumis Global Pharmaceuticals of Wuhan in China’s Hubei province was warned following an inspection last September that identified multiple deviations from cGMP. These included: failure to transfer all quality or regulatory information received from API manufacturer to customers by omitting their details on Certificates of Analysis (CoA), while copying and pasting analytical results from manufacturers’ CoA onto its own letterhead; failure to control the API repackaging, relabeling and holding operations in order to avoid mix-ups and loss of API identity; and, the quality unit failing to ensure that relabeled API was cGMP-compliant.
The FDA also warned Lumis for misbranding by naming itself as the manufacturer, distributor and packer of gabapentin API, when all of this was actually done by others. It was noted that Lumis had declared itself to be the manufacturer of a U.S. Pharmacopeia API for import into the U.S. when the actual manufacturer was on Import Alert.
Both firms were warned that their APIs were deemed to be adulterated under the definition of the Federal Food, Drug & Cosmetic Act and were strongly recommend to engage a consultant qualified to evaluate their operations and assist them in meeting cGMP requirements. Both are now on Import Alerts and the agency may withhold approval of any new applications or supplements listing them as a drug manufacturer until all deviations are corrected and compliance with cGMP is confirmed. A long list of expected responses was sent to each.
Falsified CoAs were the subject of another warning to a Chinese company, Suzhou Pharmaceutical Technology, earlier this year. The company, based in the city of Suzhou near Shanghai, was also warned for its failure even to have a Quality Assurance unit to test APIs, instead letting sales personnel sign off on CoAs under the title ‘Quality Control Director.’
Other Indian firms under FDA scrutiny earlier this year include Wockhardt, whose sterile injectables facility at Shendra was noted to be facing data integrity issues. In this case, the company received an untitled letter highlighting problems that should be addressed before more serious action is required, rather than a warning letter demanding immediate action. However, Wockhardt is now the subject of six warning letters at seven plants dating back to 2006, including a recent one at Morton Grove Pharmaceuticals in Illinois.
Megafine Pharma is another firm to receive more than one letter. In February, it had its second in the space of ten months for multiple issues at its site at Vapi in Gujarat state, including falsified QC data, shredding of documents without any record of the reasons and unclean equipment, among other things.