Virtually all organic molecules exhibit polymorphism and the solubility and bioavailability of different polymorphs can differ. Extreme care should be taken to select the most stable polymorph for all clinical trials and design a process that consistently delivers this polymorph.
Example of Skills and Experience
A new enantiotropic metastable polymorph was identified during the development of a topical drug. Proving equivalence of this new polymorph carried a high risk of failure. A full understanding of the solid state landscape was created. The transformation kinetics between the 2 polymorphs was studied and this was used to design a seeded cooling crystallisation to deliver the most stable form. Seeding was the critical element of the control strategy. Without this new process the regulatory approval for commercial production would have been in jeopardy.
The classic example of polymorph control is Ritonavir, see https://doi.org/10.1021/op000023y