FDA / clinical trial Exposure to NDMA after taking ranitidine

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@kpcross @AndyT recent regulatory highlight has been very well received by the community. Several discussion threads related to topics raised there.

Regulatory Highlights(OPR&D)

Limits calculation a true mystery, help to understand NMPA?

Hi Everyone, I am really trying to understand the where ‘correct limits’ are been calculated by regulatory bodies. A recent regulatory highlight article author by @AndyT, it’s raised the concern about differences in limits for NMPA (CAS 614-00-6) between FDA / EMA / Lhasa database. I am adding here ANVISA to the mix. His paper referenced: “Limit calculated on the basis of the harmonic-mean TD50 derived from the Carcinogenic Potency Database (CPDB)”… Now please bare with me, I’m not a to…

The Ranitidine worked referenced Searle et all demonstrated that NDMA is formed because of an intermolecular degradation reaction in solid-state. What is fascinating to me is the link between NDMA rate of formation and the crystal morphology, with columnar crystals exhibiting the slowest rate of formation.

https://doi.org/10.1021/acs.oprd.0c00462