BACILLUS CEREUS RECOVERED FROM APPLICATOR USED TO MANUFACTURE NON-STERILE ALCOHOL PREP PADS
OBSERVATION 1
Each lot of a component that is liable for microbiological contamination that is objectionable in view of its intended use is not subjected to microbiological tests before use.
COMMENT
211.065(3) (d) and 21 CFR 211.113(a) discuss the need to test components prior to their use as well as prevent objectionable microorganisms from products not designed to be sterile. In addition, because of the recent Triad Group gauze pad issues, and, that competitors meet CURRENT GMPs, the FDA assumes that all companies manufacturing both non-sterile and sterile products composed of gauze perform “due diligence” in the Quality Control of their in-coming components (raw materials) as well as with the finished product that may contain what the FDA now deems a “specified” microorganism, i.e., Bacillus cereus.
Specifically, MedWatch Report #456119 was filed on a patient with hemophilia who developed Bacillus spp. bacteremia after receiving Factor 8 infusion. The hospital reported to find Bacillus spp in PDI alcohol prep pads, Lot#11100055. Your company confirmed such finding and also found the same species, Bacillus cereus, in additional PDA Alcohol Prep Pad finished product, Lot# 11100515, 11003269 11003222 and 11002166. Your root cause analysis for Alcohol Prep Pad Product family dated 05/24/11 demonstrated that Bacillus cereus was recovered from the applicator used to manufacture the alcohol prep pads. However, your correction action and prevention action from your non-conformance report #NYH-11-0131 addressing the recovery of Bacillus cereus in the non-sterile PDI Alcohol Prep Pads does not propose any necessary changes to include microbiological testing on each lot of applicator use in the production of both non-sterile and sterile alcohol prep pads as your Work Instruction QAS-012 approved in July 2008 “QA Raw Material Inspection testing and Disposition” 3.1.13 states (b)(4). As the result none of the applicator lots used in the production PDI Alcohol Prep Pad finished
Product, Lot# 11100055, 11100515, 11003269 11003222 and 11002166 had a microbiological testing preformed prior to making into the finished product.
COMMENT
Non-sterile alcohol prep pads contaminated with Bacillus cereus, as noted with the hemophiliac who developed bacillus spp. after receiving Factor 8 infusion, demonstrates that non-sterile gauze impregnated with 70% alcohol will not kill all microorganisms
on the gauze surface and may cause injury to the patient. When the Company confirmed this as noted within this Form FDA 483, their lack of microbiological testing prior to the
manufacture of the final product and their lack of notification to the FDA and the public until interaction between PDI and the FDA over several months, demonstrates the lack of authority that the FDA possesses in requiring Company recalls. Similar issues resulted within the Triad Group recalls which ultimately bypassed the Warning Letter sequence and went directly to a seizure and Consent Decree. The release of a number of PDIs Form FDA 483s by FDA also represents a good indicator of PDI’s lack of willingness to readily participate and cooperate with the FDA.
OBSERVATION 2
The written stability program for drug products does not include test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability.
Specifically, your Standard Operating Procedure (SOP) QAS-017 entitled “Marketed Product Stability Program” 7.1.7 states, (b)(4). Such SOP is found to be deficient for it fails to monitor the microbiological aspects of the drug product s throughout the proposed shelf life. As the result, any possible out-of specification microbiological testing results that could occur after product release and during stability will not be captured until after expiry.
FDA assumes that all companies manufacturing both non-sterile and sterile products composed of gauze perform “due diligence” in the Quality Control of their in-coming components (raw materials) as well as with the finished product that may contain what the FDA now deems a “specified” microorganism, THE CATCH HERE IS DUE DILIGENCE FOR ALL RM AND ALL FINISHED PRODUCT, WHETHER THE PRODUCT BE STERILE OR NON STERILE. THE APPLICATOR IS NOT CLAIMED AS STERILE BUT STILL IT CANNOT BECOME THE CAUSE OF THE CONTAMINATION AND SOURCE OF THE BACTERIA.