The risk of microbial contamination is confirmed by the consistent number of recalls ordered by the FDA due to microbial contamination. From 1991 to 1998, for example, the FDA ordered 46 such recalls, an average of 6 per year. Among these recalls, 6 were in the Class I category, 25 were in the Class II category, and 15 were in the Class III category. As an example, a recall was recently issued for four lots of cefazolin for injection. Cefazolin is an injectable antibiotic used in a hospital environment to treat skin and respiratory infections. Certain lots of the active ingredient used to manufacture the product were shown to contain microbial contamination (Bacillus pumilus, Staphylococcus homin-is, Propionibacterium acnes, or Micrococcus luteus). The contaminated products posed a serious or life-threatening risk for some patients. The recalled lots contained 379,975 vials.
The most common microbial testing applications in the biopharmaceutical manufacturing environment as identified by the survey cited above are environmental monitoring, including class A and B cleanrooms cited by 65% of respondents, non-sterile products, such as water for injection (WFI), purified water (PW), and buffers, cited by 57%, raw materials cited by 46%, and sterile products cited by 43%.
The survey respondents identified qualitative analysis (30%), quantitative analysis (72%), and identification (35%) as key applications. The numbers add to greater than 100% because survey respondents felt that more than one application was important so they were allowed to select more than one answer. The most common conventional microbial detection method involves overfilling an agar plate with media and then pressing the open side of the plate against the surface to be monitored.
This approach typically provides about 60% recovery, but has the disadvantage that the potential exists to contaminate the surface being measured. An alternate approach involves rubbing the surface with a cotton swab. This approach greatly reduces the risk of contamination, but recovery is typically only 20%. The traditional methods take about 15 to 20 minutes to prepare the sample, a few minutes to plate the sample, 7 to 14 days for incubation, and then 15 to 20 minutes for analysis.
An advantage of the conventional method is that it does not require any capital investment. Its greatest drawback is the amount of time required to obtain results. It often does not make sense to hold up the manufacturing process until the microbiological tests have been completed. The result is that millions of dollars may be invested in materials and processing expenses that will be wasted if the results show that microbial contamination was present. The dangers to consumers of the product as well as monetary costs and risks to the manufacturer’s reputation will of course be far greater if the product should be shipped before the contamination is discovered. Another disadvantage is that conventional methods depend on the operator to follow proper procedures in collecting the sample, preparing the plate, and analyzing the results.
From: “The Advent of Rapid Microbiological Methods: Background, Applications, and Validation“
