It was interesting to hear this week of the FDA refusal to review a recent NDA application due to a lack of data on metabolism and metabolite activity. http://blogs.sciencemag.org/pipeline/archives/2018/06/14/finger-pointing-at-celgene
In recent years it has become routine to perform comprehensive biotransformation studies early in drug development to ensure that issues such as this are known and are addressed. In-vitro metabolism studies can give an early flag of potential issues however, as the article states, metabolite identification in plasma samples from the first time in human Phase 1 studies, and comparison of that data with the safety testing data, are key activities. This will flag any disproportionate metabolites, as well as indicate any pharmacologically active metabolites. In these cases, further studies would be performed to address these findings, such as studying the active metabolites.
There is guidance such as the FDA MIST and EMA ICH M3(R2) documents to enable companies understand what is required.
At Concept Life Sciences, our capabilities can help both small biotech to large companies provide the relevant data. Our high resolution LC-MS can be used to identify metabolites through the drug development cycle, and we can utilise radiochemical profiling to provide quantitative data. Our GLP & GCP bioanalysis facility, can be used to provide the necessary data on active and disproportionate metabolites as part of a regulatory submission. Our staff have many years’ experience in this area, many of these has been gained in large pharma companies.
If you would like to speak to our experts to find out more please contact: David.Higton@conceptlifesiences.com