November 22, 2021 PAO-11-21-CL-08
Interest in biologic drugs was already increasing before the COVID-19 pandemic, and growth of this market has only accelerated as companies have sought to develop vaccines and therapeutics targeting the SARS-CoV-2 virus. The need to rapidly deploy manufacturing capabilities for these products has dramatically increased the implementation of single-use technologies (SUTs) on the commercial scale. Outside of COVID-19 treatments, many of the new biologics are targeted therapies aimed at treating smaller patient populations. As such, smaller volumes of drug product are required, and SUT solutions are often preferred for new facilities constructed today.
As a result, Markets and Markets predicts that the value of the global single-use bioprocessing market will increase at a high compound annual growth rate (CAGR) of 20.5% from $8.2 billion in 2021 to $20.8 billion by 2026.1 Demand for single-use (SU) bioreactors, meanwhile, is expanding at a CAGR of 13.5% and will surpass $1.5 billion by 2026, according to Transparency Market Research.2
There are certain conditions ideally suited to SUT implementation. SUT is most widely used for biologics production but rarely implemented for the manufacture of chemical APIs due to the potential for more interactions and degradation of the plastic biocontainers and other components.
Until recently, 2000 liters was the maximum single use bioreactor (SUB) available on the market. Today, that has increased, with SU bioreactors up to 6000 L now available, with the first 6,000-L SUB installed at a new contract development and manufacturing facility in China in 2020.4 Few SUBs of this scale are in use, however, with most manufacturers electing to stick with SU bioreactors of 2000 liters and smaller.5
Because SUT eliminates the need for cleaning and cleaning validation, as well as steam sterilization and all of the supporting infrastructure, this greatly minimizes the risk of cross-contamination. This makes SUT ideal for multipurpose facilities producing many different lower-volume products and frequently switching between products in a given bioreactor. For established high-volume products that require numerous batches per year, stainless-steel (SS) bioreactors are often still preferred.
As long as SU supply is not constrained, the time and cost for establishing new SU facilities are much less than those for plants dedicated to stainless-steel bioreactors. However, the availability of SU components is currently a concern given a confluence of current events including: supply disruptions caused by shutdowns and reduced production as the result of the COVID-19 pandemic; the dramatic increase in SU implementation by COVID-19 vaccine manufacturers at commercial scale; and COVID-19 projects receiving top priority above all others, meaning SUTs are in high demand.
The elimination of cleaning processes between products simplifies the scaling of SU bioprocesses. The need to demonstrate equivalent cleaning through the cleaning validation process as processes are scaled to larger bioreactors is eliminated. As a result, scaling can be accelerated in SU systems compared with SS, which results in a faster process development timeline. It should be stressed, however, that other scaling issues related to the impacts of bioreactor size on key process parameters — power inputs, mixing gas transfer, feed rates, etc. — must be addressed when scaling in both SU and SS bioreactors.
In addition to SU bioreactors, SU biocontainers are also available for media and buffer preparation and for storage and transfer of bioprocess fluids. In addition, integrated SU assemblies are now available for most downstream processes, from chromatography to tangential-flow filtration. In addition to traditional filter solutions, which have always been SU, suppliers have developed SU membrane technologies that provide elegant solutions with improved performance over older, traditional filters.
The ability to employ SUT across the entire upstream and downstream workflow dramatically simplifies process setup, due to the elimination of any cleaning and cleaning validation requirements. Similarly, switching from one product to another in a multiproduct facility is facilitated for the entire process.
Scorpion Biological Services is an integrated contract research, development, and manufacturing organization (CRDMO) focused on cell- and gene-based therapies and large-molecule biologics. We provide a broad array of biologic manufacturing, analytical, and R&D services from our San Antonio, Texas, facilities using American equipment, reagents, and materials.
Our new clinical manufacturing facility in San Antonio will be fully SU, other than utilities and a SS autoclave system, with SU bioreactors with a capacity of up to 2000 L.
The Scorpion clinical manufacturing facility is planned to be operational in mid-2022. Scheduling and planning can be challenging given the current supply constraints. We have ordered millions of dollars of SU stirred-tank supporting equipment that will be installed months before our SU bioreactor bags arrive, as the latter will not be available for nearly one year. The goal is to have preordered everything so that materials arrive and are in inventory when we are ready to be up and running.
Chris Barnett has more than 35 years in the biotechnology industry as a molecular biologist, protein chemist, analytical biochemist, physical biochemist, formulations, and process engineering. He has extensive background in R&D program management, process development and technology transfer to manufacturing, in both the industrial and pharmaceutical arena. As Senior Director, Chris provides technical and business leadership for all aspects of process development, technical transfer, and analytical methods development for regenerative medicine products for phase I and phase II clinical testing.