Perrigo Extended-Release Acetaminophen Launch Delayed By QC Issues

Perrigo has postponed its plans to market private label extended-release acetaminophen until it can resolve quality control issues outlined in a recent FDA warning letter.

The letter, dated Aug. 16, identifies a series of shortcomings in Perrigo's Quality Control Unit (QCU) that FDA Detroit district investigators observed during an inspection running from April 26 to July 14.

The decision to halt its early production of extended-release acetaminophen tablets follows the company's recall of 115,836 bottles of extra strength acetaminophen in two actions last November (¹ and ² ).

A Class II recall was necessitated by the presence of mold (penicillin) on tablets that caused discoloration. A Class III recall of a 71,100-bottle lot of caplets was initiated because some bottles were mislabeled as ibuprofen.

The warning letter specifically addresses the second recall, noting the firm's "quality assurance auditor failed to adequately identify all product involved in a labeling mishap, which resulted in mislabeled product being distributed and eventually being withdrawn." Perrigo noted both recalls have been completed.

The Allegan, Mich.-based firm also recalled 10,452 bottles of Marquee throat spray in January due to missing "tamper-resistant protection" and conceded problems with its QCU could have been related to that recall as well (³ ).

Perrigo's ANDA (75-077) for 650 mg extended-release acetaminophen tablets was approved by FDA in February; the company had planned to launch the product in July (⁴ (Also see "Private label extended release acetaminophen" - Pink Sheet, 6 Mar, 2000.)).

The private label analgesic would have been the first available generic comparable to McNeil's Tylenol Arthritis Extended Relief caplets.

FDA's warning letter claims its investigators "documented deviations from Current Good Manufacturing Practice regulations" during their visits to the company's Allegan facility that cause Perrigo's drug products to be adulterated.

The company, for example, does not "complete product evaluations annually and Standard Operating Procedure...does not require review of all cGMP data," FDA investigators state.

The agency also charges Perrigo with not having "adequate procedures for investigating the failure of a batch or any of its components to meet specifications," citing the production problems with its extended-release acetaminophen.

"For example, the QCU failed to decide on the significance of in-process granulation dissolution test failures for coated acetaminophen raw material used in the manufacture of acetaminophen extended release tablets," the letter states.

"Production of finished product continued in spite of all indications that the coating process was not consistent and reproducible," FDA observes.

The company outlined its corrective action plan in a July 27 letter written in response to an early review of FDA inspection reports. While FDA acknowledges Perrigo's commitment to correct the problems outlined in the warning letter, the agency states it is "concerned...that your firm not only react to FDA inspections, but that the QCU be proactive."

The corrective action plan as described "fails to acknowledge the significant role of the [QCU] in the cited deficiencies," the agency says.

"The continuing pattern of the lack of complete investigations and resolution of failures and deviations by your [QCU] must be addressed," FDA insists. The agency also stresses "pending NDA, ANDA or export approval requests may not be approved until the...violations are corrected."

Representatives from Perrigo met with FDA on Aug. 23 to elaborate on its corrective action plan, which also would apply to Perrigo's two other Michigan facilities that were not included in the FDA inspections. The status of Perrigo's extended-release acetaminophen was discussed at the meeting as well.

The company said its efforts would address all areas of quality control, not only the specific criticisms made in the warning letter.