Actavis Totowa, LLC, Little Falls, NJ, Aug. 15 (New Jersey).

An FDA investigation Jan. 10 through Feb. 8 was conducted to determine Actavis Totowa's compliance with post-marketing, AE-reporting requirements for drugs.

FDA found that Actavis Totowa did not have an approved, abbreviated NDA to comply with certain reporting and recordkeeping requirements, and had failed to submit AE reports to the agency, as required.

Specifically, the agency noted six potentially serious and unexpected AEs dating back to 1999 for products, such as, digoxin, phentermine, and phenazopyridine, which were not reported to FDA.

The inspection also found the firm failed to submit complete and/or accurate information on some 15-day alert reports submitted; and it omitted required information in the reports it did submit, such as, previous conditions of patients, concomitant medications, event recurrences and follow-up information obtained from patients' physicians.

Furthermore, the company did not promptly investigate serious and unexpected AEs. Specifically, in two cases where the patients' AEs had not resolved when the firm received the initial reports, and in one case where only minimal case information concerning a fatal AE had been initially reported to the firm, there were no follow-up investigations.

Moreover, FDA noted that Actavis Totowa failed to adequately review AE information data received from all sources, such as, spontaneous reports or clinical trials; and it failed to file periodic safety reports. The agency pointed out that Actavis failed to report periodic safety reports for at least 26 AEs.

Finally, the agency said the firm had never developed procedures for the surveillance, receipt, evaluation or reporting of AEs. This included a lack of procedures regarding follow-up investigations, adequate completion of MedWatch forms, maintenance of records to assure timely submission of 15-day reports, and evaluation of AE data for serious outcome and event expectedness.

FDA acknowledged receipt of a Feb. 28 response letter, but deemed it inadequate because it neither included details that were discussed during the inspection regarding AE handling nor did it identify the cause of observed deficiencies with regard to post-marketing reporting requirements. AE, NDA, QC/QS; Doc. 13936W

Actavis Totowa:

* Did not have an approved, abbreviated NDA.

* Failed to submit AE reports to the agency.

* Never developed procedures for the surveillance, receipt, evaluation or reporting of AEs.

* Did not promptly investigate serious and unexpected AEs.