Good News/Bad News For Excedrin, Interceptor Users

Process validation is under way for Excedrin at the Novartis manufacturing facility in Lincoln, Nebraska, according to company CEO, Joseph Jimenez. That’s the good news.

The bad news for long-suffering devotees of this over-the-counter pain relief medicine is that the product will not be available in stores until October.

Jimenez gave this update during the Novartis 2nd Quarter conference call earlier today (July 19th). In addition to Excedrin, the company is in the process of product validation for Sentinel, a heartworm prevention pill. It, too, should ship before year-end.

Bad news for many pet owners is that Interceptor, a heartworm prevention pill that competes with Sentinel and also was manufactured at the same production facility, was not mentioned at all during Jimenez’s presentation. This does not bode well for its return to the marketplace in the near future. One San Diego veterinarian was told by his wholesale supplier not to expect Interceptor back on the market before 2013. The supplier’s representative explained that Sentinel, which contains the same active ingredient as Interceptor, is a higher margin product for Novartis and will have priority over the less profitable drug.

Novartis announced a massive product recall and was forced to halt production at the Lincoln plant in January 2012, as a result of packaging mixups and broken or chipped pills. An FDA inspection carried out in January found numerous repeat violations and deficiencies in the plant’s operations and quality control systems. It is taking the company several months longer than it originally hoped to address all of the issues listed in FDA’s 23-page long inspection report. But the end is apparently in sight.

Excedrin users will just have  to hang on for a few more months…..

Excedrin Return Still Months Away

Novartis hopes to gradually restart production at its Lincoln, Nebraska manufacturing plant as early as May, and resume shipping some products at mid-year. But a return to full production will probably not happen until 2013.

Production will restart on a line-by-line basis, according to David Epstein, Division Head of Novartis Pharmaceuticals, who offered a status update during the Novartis 1st Quarter 2012 Earnings Conference Call earlier today (April 24th)

“[W]e are in the middle of quality remediation activities at Lincoln,” Epstein said, “and we are making good progress. We had a meeting with the FDA recently, and shared with them our startup plan for the plant. We will begin production in May and we will resume shipments mid year.”

Epstein indicated that the “ramp up” would be slower than expected. “We’ll have a relatively limited portfolio in the back half of the year. So we have signed up some third-party manufacturers for some key products,” he explained. Neither Epstein nor any other participant in the conference call specified the order in which Excedrin and other products manufactured at that plant would reappear. Nor was there any indication as to which products would be farmed out to third-party manufacturers.

Novartis suspended production at its Lincoln facility on January 8, 2012 and recalled more than 125 million bottles of Excedrin and other OTC medications after a FDA inspection revealed flagrant and long-standing deficiencies in the company’s quality assurance and consumer complaint procedures. The shutdown of the Lincoln plant also has affected availability of a number of veterinary products, including Interceptor, a popular medication for preventing heartworm in dogs and cats.

I asked FDA for a description of the steps usually undertaken in a situation such as this one. After making the usual disclaimer that “FDA does not comment on an ongoing investigation,” Shelly Burgess of FDA’s Office of Public Affairs offered the following explanation:

“FDA investigators conduct routine inspections at drug manufacturing facilities to determine, among other things, compliance with the current good manufacturing practice regulations. When the investigator finds significant deviations from those minimum standards, he or she lists the deviations on a document called a form FDA 483, or the “483,” and issues that to the manufacturer at the conclusion of the inspection. By providing this notice, the Agency gives a manufacturer the opportunity to take voluntary and prompt corrective action. The manufacturer may submit a written response to the Agency explaining how it has corrected the violations or plans to do so, or explain why it disagrees with any of the listed observations. In most cases, manufacturers comply voluntarily but in some instances FDA sends the manufacturer a warning letter or an untitled letter. In addition, where appropriate, FDA may pursue enforcement action such as seizure and injunction.”

“The timeline can vary considerably depending on the extent of the corrective actions that are required for the firm to achieve compliance and demonstrate sufficient controls over manufacturing to produce acceptable quality drugs. Some deficiencies can be corrected within hours or days of notification such as when re-training an employee or fixing a piece of equipment. Other corrective actions may take days or months, such as qualifying a complicated manufacturing operation or validating a new test method.”

It’s not surprising that the restart in Lincoln will be slower than Novartis had originally hoped, or that the company is being vague regarding which products will receive priority when production at the facility resumes. No one wants a repeat of the problems that led to the recalls and shutdown.

Nevertheless, the delay will result in additional headaches for consumers, pharmacists, doctors, and veterinarians as the product shortages continue.

Novartis Fiasco Affects Pet Meds, Too

The recent shut-down of Novartis Consumer Health’s production facility in Lincoln, Nebraska has affected more than just Excedrin, Bufferin, NoDoz and Gas-X products. Veterinarians and pet owners also have been feeling the impact of Novartis’s abrogation of its quality assurance and product safety responsibilities.

Since issuing its product recall notice on January 8, 2012, the company has twice sent Dear Doctor letters to the veterinary community. The first letter, dated January 10th, warns veterinarians that the temporary suspension of production at the company’s Lincoln, Nebraska plant would affect the availability of certain Novartis Animal Health products. The letter begins:

Dear Valued Customer,

We are writing to inform you that Novartis Consumer Health, Inc. (NCH) has temporarily suspended production and product shipments at one of its manufacturing facilities, an action that will affect the availability of some Novartis Animal Health (NAH) products for the immediate future.

The manufacturing plant products both over-the-counter (OTC) and Animal Health products. NAH brands affected include Interceptor® Flavor Tabs®, Sentinel® Flavor Tabs®, Clomicalm®, Program® Tablets and Suspension, and Milbemite®. Production of Deramaxx, which was recently moved to the site, is also affected, although supplies on hand will continue to be shipped.

The second letter, which is dated January 25, 2012, is headed “IMPORTANT PRODUCT INFORMATION” and reads as follows:

Dear Doctor:

Novartis Animal Health US, Inc. is committed to delivering safe and efficacious veterinary products, and would like to inform you about a recent development involving CLOMICALM® (clomipramine hydrochloride) tablets.

Due to potential packaging issues at our manufacturing facility, there is a rare possibility that a wrong tablet may be found in bottles of CLOMICALM with the enclosed lot numbers. Novartis has not received any reports where a patient experienced a product mix-up, nor has Novartis received any adverse events attributable to a product mix-up. However, as a precautionary measure, we would like to extend the following recommendations.

1) Before dispensing CLOMICALM, open each bottle and examine the contents for tablets that are broken or incorrect in color, shape or size (visual guide included).

2) Post a copy of the Dear Valued Customer letter issued by Novartis Animal Health in your clinic (copy included).

3) Distribute copies of the Dear Valued Customer letter to affected pet owners. Novartis Animal Health will send your clinic extra copies upon request. If you publish a clinic newsletter, please consider using the provided notice.

4) Report any abnormal findings to Novartis Animal Health at 800-637-0281.

5) Return affected product to Novartis Animal Health; call the aforementioned number for full details.

6) Inform your clients who have already received CLOMICALM to examine tablets and refrain from administering any that are questionable in color, shape or size; and to contact Novartis Animal Health to discuss product return of affected bottles.

7) Keep records of communication with pet owners in patient files.

8) Ensure that any re-packaged tablet bottles are labeled with the product lot number.

Novartis Animal Health requests that you complete and return the enclosed Response Card reflecting that you have read and understand these points, and have discussed them with your clients.

Canine separation anxiety is a complex disorder that has great bearing on patient quality of life and the human-companion animal bond. Uninterrupted treatment is essential for successful management of this condition. Our veterinarians are prepared to discuss best practices with you in the event patients require alternative therapies, in order to minimize the risk of adverse events and potential relapse of signs.

We thank you for your attention and cooperation regarding this important issue. If you have any further questions, please contact Technical Product Services and Pharmacovigilance at 1-800-637-0281.

If you are using any of these Novartis Animal Health brands, please keep in close touch with your veterinarian to stay current on supply and quality issues.