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Formulation and Stability Prediction





Formulation and Stability Prediction

Once candidates have passed through early development and optimisation stages, it is important to understand how manufacturing, storage, transport and delivery processing steps impact product integrity and safe lifetimes.  The goal is to form a suitable buffer that confers the best conditions in which the protein molecule is most stable for these processes.  Testing, of course is best performed in real-time, however, when the ideal scenario includes testing for stability over several years, more predictive analyses become necessary.  Testing multiple formulations under a range of conditions helps rank order the effects and potentially aids understanding and prediction of long-term stability. 


Challenges of Formulations

There are many buffers and excipients available to choose from the GRAS (Generally Regarded As Safe) list, which offers a wealth of combinations, although most scientists will have a starting point in mind.  Choosing one or two types of buffer, perhaps at different concentrations and pH and then adding a few excipients also at a range of concentrations soon adds up to a significant amount of work preparing solutions.  The selected molecule(s) is then introduced at various concentrations, sometimes even up to therapeutic levels. Using automated liquid handling becomes essential with this amount of work.

The SUPR-DSF is the perfect tool for rank ordering of thermal melting points – an indicator of protein stability – on such a large scale.  Reading directly in the 384-well microplates, the formulations can be prepared in, increases workflow efficiency, reduces costs and errors from switching to alternative measuring methods and delivers fast and accurate results.  The connectivity of microplates cannot be underestimated when working with these many variations. Further, the SUPR-DSF can be easily accessed by robotic plate handlers, thus facilitating automation if required, and with its unique design and epifluorescent detection, is not affected by higher sample concentrations such as those at therapeutic levels.  With the option of running the SUPR-CM side by side, a system designed for chemical melts of the formulated samples, orthogonal data gives deep insight into the stability profiles.

Scatter plot of 96 different formulations of Infliximab. With two transitions and, therefore, two melting temperatures, the best conditions conferring stability can easily be identified.  Samples were run in triplicate in a 384-well plate in less than 2 hours.