Assignment task:
Compose a 1-2 page essay describing the risks, identifying potential impacts of the risks and categories (e.g. timelines, clinical supply, NDA approvability, budget, and commercial supply) and risk mitigation plans for setting acceptance criterion for a potent impurity outside of clinical experience.
Background Information:
Enrollment has started for two pivotal Phase III clinical studies that are evaluating safety and efficacy of Saros (sarasotastat), and Getafix Pharmaceuticals plans to submit an NDA in 18 months.
Although no changes are planned between pivotal clinical trial and commercial processes, based on manufacturing/process capability, the upper limit for the impurity S-1823 may need to be set higher for commercial product than the upper limit that was set for material being used in pivotal Phase III clinical studies.
S-1823 has the potential to impact safety and efficacy, and is expected to increase during processing due to hold time. While the proposed commercial specification acceptance criterion for S-1823 is based on prior clinical experience (≤ 0.9%), the DS/DP manufacturing process to enable the desired commercial flexibility requires an acceptance criterion of ≤ 1.5%, which is outside of clinical experience.
Prompt:
DS/DP specifications may be continually modified from clinical development through commercialization. In early clinical studies, acceptance criteria are based on results of toxicology studies, and as drug development proceeds, specifications evolve and should be based not only on clinical and nonclinical studies, but also on manufacturing experience and capability.
In the case of Getafix Pharmaceuticals, commercial acceptance criteria (purity limit) for S-1823 needs to be higher than clinical experience, since the manufacturing/process capability is unable to support limits based on clinical experience.
Outline potential risks (e.g. NDA approvability, commercial supply) and mitigation plans for the increased S-1823 purity limit, perhaps incorporating collaborations with CMC and Clinical, to support NDA approvability and commercial supply.
List the references or resources used to explain.