Is a flat, shrunken, or stuck-to-the-side lyophilized cake a problem?

It depends which one you're seeing. Slight shrinkage, where the cake pulls off the glass and looks smaller than the vial, is usually cosmetic. A review in the Journal of Pharmaceutical Sciences ("Lyophilized Drug Product Cake Appearance: What Is Acceptable?") found shrinkage and cracking trace to a formulation's mechanical properties and have not been shown to affect potency. In one case, vials with severe shrinkage tested the same as clean ones. So a cake stuck to the side isn't automatically bad. Full collapse and meltback are the worrying ones. That same literature treats both as unacceptable in a finished product. Meltback signals incomplete drying and trapped moisture, which can degrade the material and slow reconstitution. You can't tell cosmetic shrinkage from real collapse by eye. Moisture and potency testing settle it. These are research-use-only materials.