Himanshu Nivsarkar, senior manager marketing New Product Introduction, 3M Separation and Purification Sciences Division, explains the benefits and challenges of both single-use and stainless-steel bioreactors, and which is best for your facility.
Key highlights:
- Benefit of single-use reactors: can produce multiple different products in specific quantities and cut out steps in the process to increase the rate at which drugs are being produced. They are flexible in that they can change and over scale quickly and efficiently without lowering plant capacity utilisation.
- Benefit of stainless steel reactors: suitable for high mass generation over long term. Therefore, are favoured in situations where process scale varies predictably on a long term basis with limited changes.
- Challenge of single-use reactors: technology features, e.g. chromatography systems, have not been sufficiently well developed to gain wide-spread commercial manufacturing adoption.
- Challenge of stainless steel reactors: flexibility in scaling and scaling out during clinical and commercial manufacturing is difficult to achieve. This can decrease capacity utilisation rate and lengthens the response time to change in market and patient demand.
- Flexible manufacturing has led to a hybrid implementation in the biopharmaceutical industry.
In the last several years, biopharmaceutical manufacturers have faced demand for both blockbuster oncology and autoimmune drug production in large quantities, and drugs for niche disease areas produced in smaller quantities.
In addition to the challenge of competing drug types and their respective batch requirements, biopharmaceutical companies are facing other difficult choices including manufacturing setup and insourced versus outsourced commercial manufacturing. These challenges are on top of a push to lower costs on manufacturing drugs to offer competitively priced drugs.
Given the competing production priorities facing labs and the complex manufacturing of biologics, organisations are using a combination of stainless steel and single-use products to achieve the most streamlined and cost-effective manufacturing process possible. So, how do you decide which option is best for your facility?
Single-use versus stainless-steel technologies
The need to produce multiple different products in specific quantities and at a faster rate is driving the demand for single-use products. Facilities can cut out steps in the process to increase the rate at which drugs are being produced in single-use systems. However, the continued demand for building stainless steel equipment at manufacturing plants is driven by the ongoing need for large scale production.
Benefits of single-use
As the clinical pipelines of biopharmaceutical companies fill up, so does the need to produce drugs with yearly demand of about 500 kg or less. Such need dictates deployment of highly flexible manufacturing footprint that can rapidly change over between campaigns and adjust campaign length and throughput. Single use systems are ideally suited for this purpose as they can be changed and over scaled quickly and efficiently without lowering plant capacity utilisation. Additionally, single-use enables process portability from one plant to another with minimal or no adaptation.
Benefits of stainless steel
In the case where very high mass generation of biopharmaceutical to meet patient demand is key, purpose- built stainless facilities offer an attractive solution. A blockbuster drug with annual consumption of > 1000 kg requires dedicated manufacturing footprint that is capable of efficiently making the drug for many years. Because the drug-to-drug campaign changeover is not required and the process scale varies predictably over long term, one can reap the benefits of large stainless-steel systems.
Currently, stainless steel bioreactors make up 92% of installed capacity with bioreactors of more than 10,000 litres, representing 55% of total installed capacity.
Challenges with single-use
Transition from stainless steel to single-use requires development of new approaches to every single part of the process. The development in single-use bioreactors has successfully enabled single-use bioprocessing on the upstream side of the process.
Transitioning the downstream side of the process has proven to be more difficult as the single-use separation technologies, specifically chromatography systems, have not been sufficiently well developed to gain wide-spread commercial manufacturing adoption. Some very recent developments in advanced solid supports and functional ligands hold great promise in overcoming the present challenges in this area.
Challenges with stainless steel
As the product candidate pipelines expand, both in size and in diversity, manufacturing flexibility becomes more and more critical to rapid and efficient movement of the drug candidates through the development process. Such flexibility in scaling and scaling out during clinical and commercial manufacturing is very difficult to achieve using a permanently configured stainless steel infrastructure. This decreases capacity utilisation rate and lengthens the response time to change in market and patient demand.
Additionally stainless facilities have limited compatibility with various process configurations. One example is the use of stainless steel during the intensified perfusion process. Perfusion requires a cell-retention device that is based on either sedimentation or filtration. The density gradient separation techniques currently available in stainless steel products have limited options of disposable fluid path to process high-titer, high-volume processes.
Emerging opportunities
The desire to adopt single-use technologies was driven by an effort to reduce capital investment in facilities, equipment, and increase flexibility to ensure speed to clinical can be achieved. When the economic benefits were evaluated based on the parameters of speed-to-market, it negated the high costs needed for stainless steel facilities. This led to the implementation of single-use systems for clinical manufacturing and the building of new stainless steel–based facilities with scales.
Over the past several years, flexible manufacturing has led to the implementation of single-use manufacturing or stainless-steel equipment for biopharmaceutical manufacturing, driving a hybrid implementation in the biopharmaceutical industry.
In the future, biologics manufacturers will need the flexibility to respond to market, technology trends and portfolio diversity at different scales, leading to increased development of flexible, hybrid facilities.
