Many companies knowingly use inefficient spray-dried formulations to quickly enter Phase 1 trials, deferring major manufacturing and volumetric challenges until later development stages. This "good enough for now" approach often necessitates a complete, costly reformulation later on.

Fears of regulatory hurdles for new manufacturing platforms may be overstated. Regulators, familiar with technologies like molecular farming for decades, prioritize the final product's purity, safety, and efficacy. The platform's novelty is secondary to robust scientific data proving the end product's quality.

For drugs nearing the end of their patent life, creating an improved formulation with an advanced technology can generate new drug product intellectual property. This strategy protects the asset and extends its market exclusivity long after the original molecular patent expires.

By reformulating existing oncology drugs, Nenology uses the streamlined 505(b)(2) regulatory pathway, de-risking and accelerating development. Simultaneously, their composition-of-matter patents provide strong intellectual property protection typically associated with entirely new chemical entities, creating a unique strategic advantage.

A key trend in 2025's drug approvals is that "best-in-class" therapies are distinguished not just by efficacy, but by innovations in formulation and delivery that improve the patient experience. Examples include subcutaneous versions of IV drugs and new delivery methods that expand patient access.

For its oral obesity drug Foundeo, Eli Lilly gained approval for a 17mg tablet, despite pivotal trials using a 35mg capsule. The company used a bioequivalence study to justify the switch, a strategic move that halves the amount of active ingredient needed, preemptively addressing massive supply chain challenges.

Acadia's experimental drug, Remlefanserin, was designed specifically to address the limitations of its marketed drug, Newplazid. By eliminating a side effect (QT prolongation) that capped the dosage of the original drug, the new molecule can be tested at higher, potentially more effective, exposures, demonstrating a strategy of iterative, targeted improvement in drug development.

A drug's manufacturing process is not static. Over a 10-20 year lifecycle, it will inevitably change due to raw material shifts or optimizations. Therefore, continued verification (PV Stage 3) is crucial for actively managing these expected deviations to maintain a state of control, not just for passive monitoring.

Resolution Therapeutics' CEO warns that manufacturing process changes cannot wait for pivotal trials in cell therapy. The drug product used in a Phase 1/2 study must be highly comparable to the final commercial version to avoid extremely costly delays and extensive comparability studies later in development.