Last month, Novartis quietly suspended production at a plant in Lincoln, Nebraska, where various over-the-counter and animal health meds are made. The drugmaker called the move a voluntary step to improve compliance and strengthen standards (back story). However, when we asked about any regulatory actions that may have prompted its decision, the drugmaker would only say its working closely with the FDA.
Now, though, we have come across an inspection report, known in FDA parlance as a 483, that was issued following an FDA visit to the facility last summer. And the details underscore why the drugmaker closed shop for an unspecified period of time. The shutdown, by the way, follows a November warning letter about "significant violations" at three Sandoz plants that made prescription meds (see this), suggesting the FDA has Novartis in its crosshairs.
So what went wrong in Nebraska? Several things. For instance, Novartis failed to open inspections into consumer complaints of foreign products found in its solid-dosage form meds. There were 26 such complaints in 2010 and 13 in 2009. And the drugmaker failed to investigate 166 complaints of foreign tablets in its meds since 2009. The FDA also noted that Novartis never found a root cause.
Moreover, Novartis failed to extend investigations into all batches of products potentially affected by any problem. One example was a mix-up involving Execedrin Migraine Tablets and Excedrin Migraine Caplets. The drugmaker did examine the incident, but the FDA maintained its conclusion that the mix-up was not within its control was not plausible, because the meds were all packaged on the same line.
What else? There were numerous instances in which Novartis failed to file so-called field alerts within three days of being notified of any problems. And the FDA determined that the failure was indicative of a pattern. Meanwhile, quality assurance was slow to review complaints - 138 reports took more than 100 days to review, according to the 13-page FDA report.
And last year, the drugmaker received 223 critical complaints and the FDA determined that none of them were reviewed properly. At one point, the FDA report uses a lot of bold letters to make put Novartis on notice by using bold letters and caps to emphasize its concerns - THIS OBSERVATION DEMONSTRATES A PATTERN OF PROBLEMS AT YOUR FIRM.
The agency also takes Novartis to task for failing to present evidence to justify its conclusions, such as product mix-ups, which the drugmaker maintained were out of its control. For instance, Novartis argued that mix-ups were due to product pilferage, but offered no evidence to support its contention, according to the FDA.
Making matters worse, Novartis failed to send postage-paid materials to consumers who make complaints. Why is this an issue? The FDA wrote that "neglecting to ship postage-paid materials to the complainant expunges any attempt for the suspect product to be returned and properly investigated by your firm." In other words, the FDA is accusing the drugmaker of trying to bury the evidence.
The agency also notes there were an inadequate number of personnel assigned or available to conduct investigations into complaints, training was inadequate for quality unit team and the process for alerting management was not routinely followed, since Novartis "corporate personnel" were not aware of product mix-ups for at least two years until last June, according to the report (read the 483 report here).
[Note to other media: please give Pharmalot credit for reporting this first. Thank you, the editor.]