Measurement uncertainty evaluation and risk of false conformity assessment for microbial enumeration tests.

Microbial enumeration tests are widely used to assess the microbiological quality of non-sterile pharmaceutical products. Despite of all efforts to guarantee the reliability of microbial enumeration tests, there will always be an uncertainty associated with the measured values, which can lead to false conformity/non-conformity decisions. In this work, we evaluated the measurement uncertainty using a bottom-up approach and estimate the consumer's or producer's risk due to the measurement uncertainty. Three main sources of uncertainty were identified and quantified: dilution factor, plated volume, and microbial plate counts. The contribution of these sources of uncertainty depends on the measured value of microbial load in pharmaceutical products. The contribution of dilution factor and plated volume uncertainties increase with an increase of measured value, while the contribution of microbial plate count uncertainty decreases with an increase of measured value. The overall uncertainty values were expressed as uncertainty factors, which provide an asymmetric 95% level confidence level of microbial load in pharmaceutical products. In addition, the risk of false conformity/non-conformity decisions due to measurement uncertainty was assess using Monte Carlo method. When the measured value is close to the upper specification limit and/or the measurement uncertainty is large, the risk of false conformity/non-conformity decisions may be significantly high. Thus, we conclude that the use of uncertainty factor in the conformity/non-conformity assessment is important to guarantee the reliability of microbial enumeration test results and to support decision-making.

Microbiological assessment and evaluation of rehydration instructions on powdered infant formulas, follow-up formulas, and infant foods in Malaysia.

A total of 90 samples comprising powdered infant formulas (n=51), follow-up formulas (n=21), and infant foods (n=18) from 15 domestic and imported brands were purchased from various retailers in Klang Valley, Malaysia and evaluated in terms of microbiological quality and the similarity of rehydration instructions on the product label to guidelines set by the World Health Organization. Microbiological analysis included the determination of aerobic plate count (APC) and the presence of Enterobacteriaceae and Cronobacter spp. Isolates of interest were identified using ID 32E (bioMérieux France, Craponne, France). In this study, 87% of powdered infant formulas, follow-up formulas, and infant foods analyzed had an APC below the permitted level of <10(4) cfu/g. These acceptable APC ranged between <10(2) to 7.2×10(3) cfu/g. The most frequently isolated Enterobacteriaceae was Enterobacter cloacae, which was present in 3 infant formulas and 1 infant food tested. Other Enterobacteriaceae detected from powdered infant and follow-up formulas were Citrobacter spp., Klebsiella spp., and other Enterobacter spp. No Cronobacter species were found in any samples. Rehydration instructions from the product labels were collated and it was observed that none directed the use of water with a temperature >70°C for formula preparation, as specified by the 2008 revised World Health Organization guidelines. Six brands instructed the use of water at 40 to 55°C, a temperature range that would support the survival and even growth of Enterobacteriaceae.