Bioburden Testing of Parenteral Product Solution

BIOBURDEN TESTING OF PARENTERAL PRODUCT SOLUTION 

The term bioburden refers to the amount of microbial flora that can be detected on an item or surface or in a solution. The microbial recovery method used depends on the type of material being evaluated. Aerobic bioburden counts in parenteral solutions are obtained by conducting the total aerobic count and total yeast and molds count as specified in the USP microbial limits test ( 61 ) or a equivalent compendial test. Alternatively, a modified membrane filtration technique can be used to allow filtration of larger volumes of solution to assess bioburden recoveries where sample results are expected to contain a negligible number of microbial flora from the overall solution. 

In this section only the bioburden determination of a parenteral product solution for aerobic isolates is discussed and details regarding bioburden testing of facility or equipment surfaces are not included. For parenteral products, bioburden is usually estimated on the unfiltered bulk product solution (UBPS). In this way the test will indicate the total microbial load culminating in the batch solution as a result of the various contributing factors such as all batch ingredients, manual manipulations, and environmental fallout. Testing of filtered bulk parenteral solution either before or after filling into the final container may be done for comparison to the previously tested unfiltered bulk solution or to comply with the directives from European inspectors. All isolates should be identified to the species level whenever possible. The 

Microbial limit tests, as described in USP 24-NF 19 ( 61 ) provide the information necessary to conduct bioburden counts by quantitative estimations of viable aerobic microorganisms in pharmaceutical articles, raw materials, and finished dosage forms. Consult the EP or JP for any differences in these methods from those of the USP. Note that USP ( 61 ) is currently under revision and that the next version will be fully harmonized between the USP, EP, and JP. The microbial limit test comprises the total aerobic bacterial (microbial) count (TAG), the total combined yeasts and molds count (TYMC), and tests for indicator organisms. Bioburden tests are also referred to as total viable counts. This test estimates the total number of viable (culturable) aerobic microorganisms in various items including parenteral UBPS. The total viable count is obtained by adding the counts from the TAC and the TYMC. 

The TAC can be conducted using a number of microbiological methods. These are the pour-plate, membrane filtration, and multiple tube methods. The TYMC is conducted by using either the pour-plate or membrane filtration method. The TAC for bioburden is performed by adding 10 g, 10 mL, or 10 units in SCD broth or lactose broth to make 100 mL. Aliquots of this sample preparation are transferred into four standard size (15 x 100 mm) Petri dishes. Into two of the plates 15-20 mL of molten SCD agar is poured, and into the other two the same volume of Sabouraud dextrose agar (SAB) agar is poured. 

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XVIII. BIOBURDEN TESTING OF PARENTERAL PRODUCT SOLUTION... 

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