American Pharmaceutical hit on water, environment issues.

American Pharmaceutical Partners' plant in Melrose Park, IL, received its second warning letter in just under a year, which revealed several environmental monitoring and water system deficiencies.

The Jan. 11 letter cited the firm for releasing two lots of vancomycin and one of cisplatin despite failing initial finished product release criteria for glass defects. FDA also cited a procedure that allowed up to three visual inspections for critical defects in order to meet release specifications. The agency said "similar deviations regarding release of product with the possibility of critical glass defects" were noted in the Feb. 7, 2000, letter ( Doc. 8581W).

The letter observed American Pharmaceutical released one lot of heparin sodium for injection prior to identification of an unknown contaminant in the benzyl alcohol used to process the lot. American also failed to use molds to challenge media "even though mold isolates have been identified in" a filling room.

The company also was cited for an airborne bioburden sampling scheme in its Class 100 filling areas that did not assure that results reflect conditions during actual manufacture. The letter said the investigators noted several times that an unspecified number of samples were taken with no operators in the filling area, and that an apparently inadequate sample volume of air was taken in Class 100 and adjacent Class 10,000 areas.

FDA also itemized several leaks in the firm's water-for-injection system (WFI), including in a clean steam return line and in an unspecified number of pipes leading into the main WFI storage tank.

At one point during the Nov. 1-Dec. 14, 2000 inspection, investigators "observed an operator [who] extended his arm over open, empty vials on the accumulating table under HEPA filters in the Class 100 area during filling of protamine sulfate," according to the letter.

At deadline, the company had not responded to calls for comment. Doc.. 9954W