Level: Intermediate Paolo Nencioni, Lab Technician, The Menarini Group
In general, International Council of Harmonisation (ICH) guidelines require that a drug product should be evaluated under predefined storage conditions that test its thermal stability. The storage conditions and the lengths of studies chosen should be sufficient to cover storage, shipment and use. The long-term testing should cover a minimum of 12 months’ duration at the time of submission, while the intermediate and accelerated condition should cover a minimum of six months. During development phases, more than one formulation may meet the project requirements. How can we choose the best one? Surely, we would like to choose the formulation with the longest shelf life possible. A formal ICH stability study takes six months to gain any useful responses. By performing accelerated stability studies using a higher temperature than ICH conditions, we can evaluate the behavior of some formulations in a relatively short time (not more than 30 days). With the JMP Fit Model platform, it has been possible to estimate degradation rate in function of the stress factor, arriving to a data-driven decision about the more stable formula. The estimated degradation rates have been used to predict the quality attribute values at time points and storage conditions required in the ICH guidelines. The predicted results have been compared with the actual value of one batch followed using ICH conditions, in order to verify the goodness of fit of the models. The same approach has been used evaluating together the effect of temperature and oxygen level. The models built with JMP have been used to identify the real effects of oxygen content on the critical quality attributes of the finished product.