Mammalian Host Cells for Recombinant Protein Vaccine Production Andy Cheung, Peter Graham, Grace Kristy, Sneha Mathrani
The H1N1 pandemic was a strong indicator that current vaccine manufacturing technology is not sufficient. Its shortcomings include long lead times and inconsistent yields. Due to these issues, and the potential production problems associated with using the traditional egg-based manufacturing process, alternative vaccine production methods are being researched. The production of recombinant viral antigens is one promising alternative. Recombinant hemagglutinin (rHA) influenza vaccines have been shown to shorten the vaccine production timeline by several weeks, reducing the lead-time needed for the distribution the influenza vaccine in a pandemic. Additionally this method eliminates the need to introduce the real virus into patients, it has scalable batches, and it provides consistent yields. Our goal was to design a manufacturing process, using SuperPro Designer®, that was able to produce 75 million doses of rHA (at 50 micrograms per dose) within a 34-week timeframe. From which we could analyze the Internal Rate of Return (IRR) and Net Present Value (NPV) for various selling prices/dose of vaccine. Additionally, we could then analyze the environmental impact of our facility design, using Biwer and Heinzle’s approach (2004). Our analysis is based on use of a mammalian host cell, the Human Embryonic Kidney cell line (HEK293), as a production platform for rHA. We chose production variables that were based on current research, such as 1 g rHA/L in bioreactor. Upstream and downstream unit operations as well as the process equipment were chosen to optimize yields, reduce capital costs, and reduce the environmental impact. The design produced an overall yield in downstream processing of 40% (allowing the specified number of doses to be produced in 10 batches over a period of 31 weeks), an IRR of ~170% and an NPV of ~$550,000,000 at $1.00/dose, and a General Effect Index (GEI) of 1.008 for process inputs and 1.021 for process outputs. The results of this design are promising based on production timeline, economics, and environmental impacts.