A comprehensively validated IVRT method reliably discriminates sameness and differences between several topical clotrimazole creams.

In vitro release testing (IVRT) has gained increasing acceptance for use as a biowaiver for topical products intended for local action. Whereas the United States Food and Drug Administration (US FDA) has issued product specific guidances (PSGs) recommending IVRT for several products, the PSG for clotrimazole cream does not include an IVRT option. However, an important requirement to include supplemental selectivity in the validation process as described in the recent FDA draft guidance on IVRT studies for topical drug products has generally been conspicuously absent in the published literature describing the application of IVRT as a biowaiver.

Synthetic Cassettes for pH-Mediated Sensing, Counting, and Containment.

As pH is fundamental to all biological processes, pH-responsive bacterial genetic circuits enable precise sensing in any environment. Where the unintentional release of engineered bacteria poses a concern, coupling pH sensing to the expression of a toxin creates an effective bacterial containment system. Here, we present a pH-sensitive kill switch (acidic termination of replicating population [acidTRP]), based on the Escherichia coli asr promoter, with a survival ratio of <1 in 10.