Mike Lee, Milestone Development Services, Clare Murray and Amhed Abrahim, SCYNEXIS, Graham McGibbon and Ryan Sasaki, ACD/Labs, Inc.
Within the pharmaceutical industry, the rapid identification, elucidation, and characterization of synthetic or process impurities or degradants is an intense and comprehensive undertaking. In the development of a formulated drug substance, the FDA requires that all impurities introduced in the proposed process above 0.1 by area percent need to be isolated and fully characterized. Furthermore, in order to develop a robust drug product, degradants must be characterized with the intent of minimizing their presence (thus preserving the shelf life of the formulated drug product)[1]. The emergence or presence of unqualified trace impurities or degradants in a drug product can grind development to a halt. Unambiguous determination and characterization of impurities and their fate and impact must be fully understood and communicated to regulatory authorities.
According to a recent FDA letter to industry, 54% of drug shortages were due to quality issues [2]. Improving the overall productivity of drug discovery, development and acceptance requires a combination of strategies, but even moderate improvements can substantially increase returns [3]. Knowledge of the synthetic route and additional experimental components of the impurity profile can prove invaluable in speeding the isolation and subsequent identification of an impurity. Software tools can also be employed to help speed up analysis and interpretation to ensure turnaround times on structure elucidation requests are minimized. In silico screening may be employed to asses the potential impact various impurities may have on the efficacy of a pharmaceutical agent to prioritize further testing when toxicology data is limited or lacking [1]. Collaboration can enhance scientific productivity when collaborators bring special expertise and knowledge crucial to the research outcome, and in situations where there is a joint use of specialized equipment. Each of these strategies, and the resulting ability to deliver a drug to market in less time, requires that scientists must be able to obtain the highest quality data possible in the shortest amount of time.
Advances in laboratory hardware, software, and informatics technologies are changing the way in which scientists work together to help resolve impurities in a quick and efficient manner. In addition, the industry's trend to towards externalization and outsourcing of development tasks provides a more cost-effective method, however this brings new challenges with regards to communication, collaboration and data management towards a new model that balances knowledge sharing and IP protection.
The goal of this session is to share best practices in the industry as well lessons learned in this ever-changing landscape. New perspectives on how a Unified Laboratory Intelligence [4] model based on new and existing technologies can be effectively leveraged to best aid workers in a multi-disciplinary environment and for working with partners will be discussed. In addition, a series of case studies will be presented. While the case studies will have a pharmaceutical drug development focus, we invite attendees from all industries dealing with impurities to participate and offer their perspectives and current challenges.
