API Development and Manufacture – Late Phase
Supporting Late Phase API Development and Commercial Launch
We have an established reputation for developing processes for late clinical stage. Our extensive experience lies in taking processes from inception through to process validation, both in small molecule chemistry and peptides. As an API moves from early clinical phase towards late clinical phase, the emphasis of the project changes. Whereas in early clinical supply, a lean fit-for-purpose approach is appropriate, other factors start to dominate when moving towards late phase, particularly process efficiency and knowledge. We strategically integrate the principles from regulatory guidelines (FDA, ICH, USP), such as risk management and quality by design, as a basis for development and manufacturing strategies.
To improve process efficiency, our chemists can perform process optimzation and intensification with the goal of increasing yields, reducing raw materials and waste, and simplifying process operability. Once the process starts to become established, the focus changes so that knowledge and understanding become the primary objectives, ensuring the process is robust.
Implementation of the following themes include:
- Purge and fate studies
- Hold point studies
- Identification of critical process parameters
- Design of experiments
- Development of control strategy
Part of the process understanding exercise is to gain an in-depth knowledge of the impurities generated, as well as, understanding their fate. Impurity identification is performed using our wide array of analytical techniques, particularly LCMS and NMR. Impurities can then be either synthesized using traditional chemical synthesis or isolated from process streams using preparative chromatography (column chromatography or preparative HPLC). The impurities are then characterized and can be used as reference markers / standards.
Analytical Development Optimzation
Analytical methods will continue to be enhanced during this phase of development and will undergo full ICH validation.