An alternative sterility assessment for parenteral drug products using isothermal microcalorimetry

作者：Brueckner D; Krahenbuhl S; Zuber U; Bonkat G; Braissant O^*

来源：Journal of Applied Microbiology, 2017, 123(3): 773-779.

DOI：10.1111/jam.13520

• bacteria
• contamination
• drug safety
• isothermal microcalorimetry
• public health

AimsProduction and release of injectable drug solutions are highly regulated since the administration of injectables bypasses natural body barriers. The sterility test is the last opportunity of product quality assessment. However, sterility is currently assessed by visual inspection (VI) that is time consuming and somewhat subjective. Therefore, we assessed isothermal microcalorimetry (IMC) as a replacement for the VI of the filtration based state-of-the-art sterility control.
Methods and ResultsWe used ATCC strains and house isolates to artificially contaminate frequently produced monoclonal antibodies (Avastin, Mabthera, Herceptin). After filtration, growth was assessed with IMC. Growth of all micro-organisms was reliably and reproducibly detected 4days after inoculation, which was significantly faster than with VI.
ConclusionsThe reliability and the sensitivity of IMC have a large potential to improve sterility controls. Further evaluation of this alternative method is therefore highly recommended.
Significance and Impact of the StudyDrug safety is of great concern for public health. Faster and safer drug production could be achieved using the technique described here. All the tests were performed with real manufactured drugs and complied with pharmaceutical standards. This suggests that drug sterility testing can be improved with potentially increased safety and cost reduction.

• 出版日期2017-9