Phrase: "Adequate" and "Inadequate"
Inadequacies sprout like weeds in warning letters. Indeed, in a warning to Gilead Sciences, the QA Pharm columnist counts the word "inadequate" 18 times. The warning details problems with the drugmaker's response to a Form 483 report following the inspection of a San Dimas, CA, plant.
The inadequacies concern rationales, justifications, and timeframes, as well as details for proposed fixes, according to PharmaPro. Added up, the inadequacies yielded Warning Letter W/L 44-10.
Braintree Laboratories also saw the word" inadequate" in its buggy warning letter. "Your firm received 21 consumer complaints in 2008-2009 for the presence of foreign materials in five finished products (e.g., insects, insect parts, and spiders). Upon receipt of these complaints, you concluded that the foreign material could not be attributed to your firm's manufacturing practices. However, you did not conduct a thorough investigation to assess whether facility or raw material quality problems were at the root of these complaints." Braintree sent a response to the FDA, but the agency found it inadequate: "In your response, you state, ‘We believe that the foreign matter reported [some not verified] in the complaints do not present inherent health hazard.' FDA considers contamination of finished drug products with foreign material (e.g., insects) a significant product quality issue."
Sunrise Pharmaceutical got some unhappy news from the FDA. GMP violations lingered at the company--inadequate process controls, lack of master production and control records, and inadequate details on training intended to prevent GMP violations combined to earn it a warning letter. The letter is part of a protracted correspondence between the drugmaker and the regulator following a month-long inspection last summer.
The regulator, among other things, points to validation studies for guaifenesin and dextromethorphan HBr 400mg/20mg caplets. The studies are inadequate in that they do not demonstrate that the manufacturing process is reproducible. "Specifically, one of your three validation lots failed the blend uniformity test specifications. This same lot was blended for an additional 10 minutes without the review and approval of the Quality Unit. In addition, the validation protocol was not approved until April 2008, which is four months after the validation lot was manufactured," according to the letter.
Teva also got warned for an inadequate response. The company was "unable to determine the cause of an out-of-trend level of bacterial endotoxin contamination found in three vials of finished propofol injectable emulsion. No corrective action was taken in response to this finding at the time of manufacture, and your firm released the lot." After the release, samples of the lot were collected, tested, and found to have bacterial endotoxin levels of an unnamed amount. This lot was recalled. The FDA says the company's Aug. 10, 2009 response was inadequate.
The regulator also expressed concern about "the inadequate investigation into the contamination of your IV drug products, process deviation, and the inappropriate documentation practices cited during this inspection."