According to the Food and Drug Administration and the Orphan Drug Designation program, orphan status applies to drugs and biologics defined as “those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the US, or that affect more than 200,000 people, but are not expected to recover the costs of developing and marketing a treatment drug.” Due to the high costs and low demands of the drug product, it is important to efficiently use API supply during the formulation process.

Dr. Elsie Melsopp, Head of Solids Formulations for Alcami, says the company successfully helped a client overcome an API supply shortage using Quality by Design (QbD) studies to successfully formulate an orphan drug product. The client needed full development and product readiness with an extremely short supply of the API. In addition, the scale-up batch was small because of the low volume of product demands of their orphan drug.

Considering that small batches present a challenge in proving the robustness of the processing equipment, the Alcami project team, in collaboration with client team members, prepared a failure mode, effects, and criticality analysis (FMECA) of the formulation and process. As a result, the team identified and prioritized studies that would provide the necessary product and process understanding needed to develop a control strategy, ensure the reproducibility of the product, and meet its intended safety, efficacy, stability, and performance profile regardless of the manufacturing scale.

The QbD studies were designed concisely to minimize the use of the API and evaluate the critical product parameters that could affect the product quality attributes of the drug product, per FDA’s QbD guidance.

“Alcami supported this product with supply constraints and successfully developed a capsule formulation for two dosage strengths,” she explains. “The formulations group performed studies at a micro-laboratory scale using a scientifically-based approach to identify a lead prototype. The results provided a formulation amenable to two dosage strengths by applying a proportional dosing weight method.” The product is currently in late-stage development with the New Drug Application filing expected in late 2021.