Understanding the Design Intent for the product is key. The route of administration, the drug solubility in biorelevant media and the proportion of drug in the formulation are all general considerations that can be used to assess risk with respect to API physical properties and guide when risk mitigation should be performed.
Some formulation types carry higher risk as their performance is very dependent on API physical properties and proving equivalence between formulations is difficult. Inhaled and intranasal drugs fall into this category. In these cases, prior to starting phase 2, full solid state understanding should be obtained and the API crystallisation developed. On the other hand, for an IV formulation of a highly soluble and stable drug, the formulation is less demanding on API physical properties and proving bioequivalency is facile. This is lower risk, hence work could be delayed into later clinical phases.
The right risks need to be mitigated at the right time.