As Novartis Animal Health warns veterinarians that incorrect tablets may be found in bottles of the anti-anxiety medication Clomicalm, highly critical reports from the U.S. Food and Drug Administration (FDA) reveal that manufacturing mishaps and failures to followup on consumer complaints are behind the temporary shutdown of the company's plant in Lincoln, Neb.

The plant's closure caused Novartis to suspend production of the antiparasitics Interceptor and Sentinel in December. Now a "Dear Doctor" letter is alerting practitioners to the “rare possibility” they might find a product mix-up affecting 20 lots of Clomicalm (clomipramine hydrochloride). 

Novartis doesn't reveal exactly what might be mixed with Clomicalm, if anything. Joseph Burkett, head of global communications for the company's animal health division, did not return phone calls or emails from the VIN News Service seeking more information.

The Jan. 25 letter follows a recall that Novartis Consumer Health issued on Jan. 8, warning consumers that chipped or broken pills might be found in over-the-counter drugs such as Bufferin, Excedrin, Gas-X Prevention and NoDoz.

All of these products — animal- and human-health medications — are manufactured in the same Lincoln, Neb., facility.

To be sure the Dear Doctor letter reaches its target audience, Novartis wants veterinarians to return a response card that accompanies it. The company advises veterinarians to closely examine their bottles of Clomicalm for broken, off-color or unusually shaped tablets. Generally, Clomicalm tablets are oblong and speckled brown. Practitioners also are being asked to post the Novartis letter in their clinics and distribute copies of a "Dear Valued Customer" letter authored by Novartis on the topic.

Any abnormal findings should be reported to Novartis Animal Health at (800) 637-0281. Press 5 for a product defect technician.

Initially, Novartis officials told the VIN News Service that production of Interceptor and Sentinel might resume mid-January. In a vague statement, "process and compliance improvement activities" were blamed for the plant shutdown in December, and officials rebuffed questions about whether the FDA was involved in the decision.

It's now clear that FDA played a major role in the plant's closure. Inspection reports released by the FDA reveal that problems with the manufacturing facility and its operators were serious, with repeated warnings from the regulatory agency about quality control problems.

According to FDA investigators, consumers had complained about tablet mix-ups, foreign objects found in containers and the suspected tampering of bottles of Novartis drugs. In one reported instance, Novartis failed to investigate a complaint that a bottle of Excedrin Migraine tablets contained caplets. Another case involved a specific lot of Excedrin Extra Strength caplets mixed with Excedrin ES gelcaps. Partial or incomplete tablets found in a lot of Bufferin RS prompted 80 consumer complaints, the FDA noted in a Jan. 20 inspection report, yet Novartis closed its complaint investigation without addressing it. The FDA report refers to nearly 1,400 consumer complaints that Novartis neglected to respond to or forward to regulators.

"Your firm was aware of partial/incomplete Bufferin tablets/capsules issues since at least 2009, yet a Medical Safety Assessment Report was not released until 10/14/11. There is no justification or explanation for the approximately two-year delay in obtaining this report," the FDA wrote to the company following a four-week inspection that started mid-December.

The FDA also cited in its report that Novartis failed to identify how a dozen extra pills ended up in a sealed bottle of morphine sulfate, which a pharmacist reported finding last November. "There are no documented preventative measures within the investigation to ensure this type of problem does not continue," the FDA noted. "This is important because this consumer complaint was recently closed and is indicative of how your firm is currently investigating consumer complaints."

The FDA's scathing remarks continued in the 24-page report to identify human errors, sloppy procedures and improperly trained employees as root causes of problems at the Novartis plant.

The agency ordered Novartis to shutdown production in the plant on Dec. 11, eight days before the company alerted the public to its closure.

In a Jan. 25 filing with the U.S. Securities and Exchange Commission (SEC), Novartis stated that the "unexpected" closure of its plant in Lincoln, Neb., so far has cost the company $200 million — $115 million in costs directly tied to the plant's closure and $85 million in lost profits.

As for the company's animal health medications, Interceptor and Sentinel included, it's unclear when those drugs will be back in production. 

"We plan to gradually resume operations at the Lincoln site following implementation of planned improvements and in agreement with the FDA," Novartis said in the filing. "However, as of the date of this Form 20-F, it is not possible to determine when the plant will resume full operations. The Lincoln facility produces a variety of products with annual sales of less then two percent of Novartis group sales.

"Should we fail to complete the planned improvements at the site in agreement with the FDA in a timely manner, then we may suffer a significant loss in sales," the company added. 

Update: After consulting with the FDA, Novartis plans to make available to U.S. and Canadian veterinarians, stocked animal health inventory that was manufactured before the company's Lincoln, Neb., plant shut down December. According to a newly released Novartis statement, those products include Interceptor Flavor Tabs; Sentinel Flavor Tabs; Clomicalm; Program tablets and suspension; and Milbemite.