Case Study: Challenges and Solutions to Formulating an Orphan Drug

According to the Food and Drug Administration and the Orphan Drug Designation program, orphan status is applicable to drugs and biologics which are 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 U.S., or that affect more than 200,000 persons 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 your API supply during the formulation process. This case study presents how Alcami successfully helped a client overcome an API supply shortage using Quality by Design studies to successfully formulate an orphan drug product. 

Client Profile

The client needed full development and product readiness with an extremely short supply of the active pharmaceutical ingredient (API). The API was in short supply and the scale-up batch was small because of the low volume of product demands of their orphan drug.

Partnering with Alcami

Alcami supported this product with supply constraints, and successfully developed a capsule formulation for two dose strengths. 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 dose strengths by applying a proportional dosing weight method.

Challenges and Solutions

Taking into consideration that small batches present a challenge in proving 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. The team was able to identify and prioritize studies that would provide necessary product and process understanding needed to develop a control strategy, ensuring reproducibility of the product and meeting its intended safety, efficacy, stability, and performance profile regardless of the manufacturing scale.

Where are they now?

The Quality by Design (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. Currently, the product is in late-stage development with the New Drug Application (NDA) filing expected in the fourth quarter of 2018.