What happens when no sufficient effort is put on CMC ?

Starting from your research lab, where you found an interesting compound that might end up into a lifesaving drug, the journey will be about 10 years to reach the market access. If the cost and global burden in a budget of clinical trials is well assumed by the entering start-ups, the CMC (Chemistry, Manufacturing and Control) is almost an unknown field.


However, this 2-year development isn’t to neglect, otherwise it could either make you never meet the Phase I, or hit hard after the NDA/BLA when receiving a CRL (Complete Response Letter, sent by FDA to put a temporary stop on a drug’s approval until specific issues are addressed). In January 2019, Immunomedics received one exclusively focused on CMC , and no new clinical or preclinical data needed to be generated. As far as I know, their Sacituzumab govitecan is still in the approval process today. ViiV healthcare and their promising cabotegravir and rilpivirine long-acting received one CRL too  , just before Christmas 2019.


According to a Nov 2018 article in Pharmaceutical Technology Europe, “large pharma companies are unlikely to make mistakes due to the resources invested early in [CMC] program management.” On the other hand, some small biotechs take the approach of “let’s run as fast as we can with whatever works, and if there is a problem, we will deal with it later” which is exactly what shouldn’t be done with CMC. Performing extensive due diligence on CMC before an asset is acquired is crucial for the valuation of the project. Otherwise, you can, by a process that cannot be scaled up, has too many impurities, not sufficient stability (you must start accelerated stab studies as soon as possible!), created with a mischaracterized cell bank, …


3Biotech has created this timeline that takes a project from theresearch stage and brings it to Phase 1, in 18 months. Here are a few major points of this timeline:

  • Start with analytical methods development. With no robust methods to characterize your compound, there is no chance to be successful in the following steps,
  • Spend time and money on the cell line development. This is the cornerstone of your development.
  • Start formulation and stability studies ASAP. Clinical trials always last longer than expected…,
Gantt chart of a drug development to phase 1.