Last month, Novartis disclosed that it received a warning letter from the Food and Drug Administration about manufacturing issues at two facilities in India that are operated by its Sandoz generic drug unit.
At the time, the company noted it was working closely with the FDA to resolve the problems. But Novartis never actually specified what bothered the agency. Now, the warning letter has been posted on the FDA website, and the infractions are concerning, especially given that the plants are run by one of the world’s largest suppliers of generic medicines.
The disclosure comes amid ongoing FDA scrutiny of overseas manufacturing plants, particularly in India, where a string of drug makers has failed inspections and had products banned from the US. The Indian pharmaceutical industry is furious that the agency appears to be singling out its ranks for infractions; however the Sandoz letter indicates the FDA is not confining its reviews to India’s domestic drug makers.
A key issue that alarmed the agency during its August 2014 inspections was the integrity of the data Sandoz was collecting. In one plant, which makes finished dosages, Excel spreadsheets were used to record discrepancies and certain quality data. But the data was initially missing in documentation and the company later entered the information and backdated the entry.
“Backdating … records is unacceptable,” the FDA wrote in its Oct. 22 warning letter. The agency also expressed concern that Sandoz failed to demonstrate the extent to which such practices may be widespread and — this is significant — whether previous data is even reliable.
Here’s another gaffe: During discussion with FDA inspectors, a contract employee — who is responsible for training other contract employees — was “unable to explain the material he was required to present during training,” the letter stated. Moreover, while a “significant number” of contract employees do not speak English, Sandoz only provided English training materials to those employees.
What else? FDA inspectors found an equipment qualification training assessment in the trash, indicating the employee had failed. But the employee’s official file showed that he had passed. What prompted the FDA to inspect the trash or the extent to which FDA inspectors engaged in extensive dumpster diving isn’t clear, though.
Meanwhile, FDA inspectors also found that Sandoz employees maintained they informed the agency that a batch of medicines did not meet specifications. But the plant’s regulatory affairs department decided not to tell the agency until after the product was approved. Not surprisingly, the FDA wrote Sandoz that its “decision to withhold information from the agency raises serious concerns.”
The FDA was also upset that Sandoz does not restrict access to laboratory data, suggesting that problematic breaches could occur and crucial product information is subject to unauthorized changes.
These were the problems found at one plant. At the other plant, Sandoz failed to “establish and follow” needed written procedures in order to prevent microbiological contamination. The company also failed to create an adequate system for monitoring environmental conditions.
We asked Novartis for comment and will update you accordingly.
UPDATE: A Novartis spokesman wrote us to say that the drug maker is in the process of updating various systems to better track data. “We take the health authority inspection outcomes seriously and have been working diligently on corrective actions at the Kalwe and Turbhe sites in India since the inspections last year, and continue to keep the FDA updated on our actions,” he said.