ESR 15 - Implementation of efficient controlled polypeptide synthesis under validated technologies

First goal of my project is to scale up sequence specific polypeptidic carriers, which will be developed by my colleagues in a lab scale. Peptides are versatile molecules that can evade the immune system and cross biological barriers, including skin, blood-brain barrier, gastrointestinal walls, can enter into the cytoplasm or nucleus of the targeted cells. Polypeptide carries investigation is primarily focused on cancer therapy, but treatment of other pathologies has also been explored (rheumatoid arthritis, etc.).  Usage of this type carriers is determined by the effect of increased permeability and retention (EPR) to improve drug delivery in tumors. 

Scaling up is a migration of a process from the lab-scale (depending on the product type it could be mg or g quantities) to the pilot plant-scale or commercial scale (from g to hundreds of kg).  With scale-up can come a number of challenges – from making sure the chemistry works in larger equipment, to eliminating new impurities, which can arise from side reactions or catalysts used. The ultimate goal is to create a production-level process that yields the best results in each batch. 

Second goal is to establish validated analytical and physico-chemical characterization acceptable that meet FDA requirements and ICH guidelines. This include not only developing a tests to ensure that finished polypeptide will comply the specification, but quality determination of the raw materials needed and process parameters which can affect the Critical Quality Attributes of desired product.