Actavis Totowa cited for failures in reporting, stability testing.

Actavis Totowa, Little Falls, NJ Parsippany District

Following an inspection Sept. 5-28, 2007, FDA Investigator Kristy Zielny issued a three-item 483 to Actavis Totowa, a maker of generic drugs.

In April 2008, the firm initiated a Class I nationwide recall of Digitek (digoxin tablets, USP) for oral use. The products are distributed by Mylan Pharmaceuticals under a "Bertek" label and by UDL Laboratories under a "UDL" label, according to a company news release.

The voluntary all-lot recall was due to the possibility that tablets with double the appropriate thickness may have been commercially released, the firm noted. Actavis said the tablets may contain twice the approved level of active ingredient than is appropriate.

According to the 483, digoxin did not appear to figure in the inspection. Instead, FDA said the company had not submitted an NDA-Field Alert Report within three working days of receipt of out-of-specification results for a lot of Carisoprodol, Aspirin and Codeine Phosphate Tablets, 200 mg/325 mg/16 mg at the 12-month stability test interval. The original OOS result was received on Aug. 21, 2007, and results were confirmed as OOS on Aug. 28, but the Field Alert was not submitted until Sept. 9, 2007.

Zielny also observed that the company did not follow its written stability testing program.

Certain lots of Meperidine Hydrochloride and Promethazine Hydrochloride Tablets, 50 mg/25 mg; Dexchlorpheniramine Maleate ER Tablets, 6 mg; Methenamine Mandelate Tablets, 1.0 mg; Chlordiazepoxide Hydrochloride and Clinidium Bromide Capsules were not tested at the 36-month stability test point, the 483 stated. The products were tested at a later date, but the cause for not conducting the testing at the appropriate time "was due to incorrect assumptions that the product need not be tested due to changes in expiration dating," the 483 stated.

Actavis Totowa also failed to follow written production and process control procedures in the execution of production and process control functions, the inspector observed. The Standard Operating Procedures "Investigation of Deviations" and "Investigation of Out of Specification Results" require that investigations be initiated when a deviation or out-of-specification result is detected and be closed within 30 days.

However, the report stated, the company did not follow these SOPs in all such situations. No investigation was initiated on Sept. 5, 2007, although a blend was placed on hold for unidentified particles. An investigation for low yield in a lot of Carisoprodol, Aspirin and Codeine Phosphate Tablets USP200/325/16mg was not begun, the report stated. The batch record was signed off as reviewed and approved by production management prior to the investigation. Investigation of Deviation Reports were issued on Jan. 19 and Jan. 29, 2007, but were not closed until May 25, 2007.

Only one interim report was written for an investigation that was open from March 14-July 21, 2007.

In addition, interim reports were not always written to document justification for investigations to remain open after each 30 day interval.

Actavis Totowa, Little Falls, NJ, 9/5-28/07, Doc. 110091, $3 plus retrieval