SelectHost, a joint project between IST-ID and FARM-ID, aimed to develop new active pharmaceutical ingredient (API) purification processes to remove genotoxic impurities (GTI) in organic solvent streams. APIs are typically synthesized using highly reactive reagents that persist as impurities in the final product. Some of those are genotoxic or carcinogenic and therefore related API administration risks for patient’s health has become an increasing concern of pharmaceutical companies, regulatory authorities, patients and doctors.

API synthetic routes include intermediate and final purification stages using conventional techniques (crystallization, chromatography, distillation). However, to reach regulated ultra-low GTI levels, these techniques lead to large API losses, with significant economic impact.

SelectHost aims to develop cost-efficient and sustainable strategies for API purification with API losses below 10% and removal of GTI down to levels that decrease patients’ risk to values below 1 in one million. However, most of the API synthesis takes place in organic solvents, posing a challenge for the design of purification processes.

Outcomes: 

SelectHost successfully developed organic solvent nanofiltration (OSN) membranes and molecularly imprinted polymers (MIP) for the removal of GTIs in organic solvent for relevant case studies, selected considering their industrial relevance. Namely, new selective hosts were developed by modifying existing polymers with the introduction of recognition and separation motives for GTIs, new MIPs were designed, and recrystallization OSN-assisted processes were developed. Separation performance was assessed in terms of efficiency and the results were used for an economic and environmental impact analysis.