Noven Pharmaceuticals, maker of the Fentanyl Transdermal System--an opioid patch used for long-term pain treatment--has come under fire by the FDA for poor process validation and for running equipment unable to perform its intended function. Warning Letter 54-11, dated last August, was recently posted to the FDA website.
The warning states that during a February visit to Noven's Carlsbad, CA, plant, inspectors found an insufficient process validation report--it lacked both mention of manufacturing deviations and an evaluation of the impact of the deviations. Among the deviations, the letter says, were brown particles found in a lab sample of the Fentanyl Adhesive Mass Solution. In addition, workers aborted cutting/packaging operations during the first process validation lot because the equipment was working improperly.
Noven replied to the FDA inspection report with a letter stating that the "deviations were not considered to have an impact on validation at the time the validation report was prepared." But the agency replies in the warning that saying so isn't enough: "You fail to provide any supporting evidence to substantiate this claim." The regulator adds that the company's technical review of the process validation "is inadequate because the contents are broad, lacks any supporting raw data, and is unclear as to what specific elements, lot numbers and records were reviewed."
Regarding the cutting machine, the FDA notes the machine was initially qualified on June 7, 2007, but some "25 major and minor changes were implemented between June 14, 2007, and July 15, 2010, before your approval of the re-qualification report." Noven replied that the machine is custom; it contains subunits that functions independently. "Modification to one subunit does not necessarily adversely impact other subunits or the equipment as a whole," according to Noven, in the letter.
The requalification requirement, according to Noven, was documented in each approved Change Control.
"You have neither provided documentation to demonstrate your claims of independently functioning subunits," the FDA says, "nor have you provided your rationale why each equipment change did not necessitate a re-qualification and/or a re-validation of the machine."
- see Warning Letter 54-11
Special Report: Frightening Phrases: Warning letter language to watch