Target Selection
The target product, BChE, was selected based on the suitability of plant cell culture operation for small to moderate drug indications, such as chemical or biological defense stockpiles and rare disease treatment. The target production level for rrBChE is 25 kg per year. With a single dose at 400 mg, this corresponds to production of 62,500 doses of rrBChE annually. The production level was estimated on the basis of stockpile generation and emergency deployment. Many orphan diseases would require similarly small production capabilities, such as alpha-1-antitrypsin deficiency, which affects approximately 100,000 people in the US (Stoller & Aboussouan, 2009), or amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, which affects approximately 30,000 people in the US (Miller & Appel, 2017).
The large-scale biomanufacturing facility designs are based on laboratory-scale data. However, process design inputs assume modest improvements in culture performance and downstream recovery based on anticipated process optimization work to be done as part of scale up to pilot and commercial manufacturing.