The continuing need to increase titers while decreasing capacity, combined with the resurgence in vaccines and the introduction of gene and cell therapies, mean that efficiency and productivity are the key elements in upstream biopharmaceutical manufacture. As these increased titers move downstream, the increased processing flexibility and reduction in the number of purifications steps afforded by single-use technology, can often be utilized to optimize manufacturing operations. Here are steps to increase productivity as well as efficiency upstream and downstream.
1. Seek to decrease downstream bottlenecks by increasing upstream productivity. Remain focused on process intensification, optimization, and expansion.
2. Upstream process intensification can be achieved with higher titers in smaller bioreactor volumes.
3. Upstream process optimization can be achieved with higher titers by optimizing gas sparging, low shear mixing, and higher cell viability and density.
4. Upstream process expansion can be achieved by replicating, at a larger scale, exact microenvironment conditions and consolidating multiple manual steps in an automated bioreactor with larger surface.
5. Seek to increase downstream efficiency through the use of best in class single-use technology.
6. Maximize vessel integrity through use of fully assembled bags and manifolds that are 100% integrity tested by pressure decay methods after assembly and before irradiation.
7. Maximize vessel integrity by use of fully assembled bags and manifolds through Helium Integrity Testing (HIT) for pinholes as small as 10 microns after assembly and before irradiation.
8. Use mixers that do not shed particles or grind contents.
Jeffery Lee Craig is global director of business development and marketing at ATMI LifeSciences.