How single-use technologies drive process optimization in biopharmaceutical manufacturing

Published on 30 Aug, 2018

Fixed stainless steel systems have been the desired choice for manufacturing high volumes of biopharma drugs for many decades due to their mass-production capability. Over the last two to three years, Single-use systems has increasingly found application in commercial manufacturing of biologics as they are low in CAPEX and more suitable for smaller and less-funded companies and even contract manufacturing organizations (CMOs). Single-use systems eliminate the cleaning process entirely, saving not only on cost associated with manual labor but also on the time required to validate the stainless steel equipment prior to re-use, thus making it more sustainable than stainless steel technology.

For decades, fixed stainless steel systems were the most pragmatic choice for manufacturing high volumes of biopharma drugs. Fixed systems rely heavily on stainless steel for piping, valves, tanks, and fittings as the parts needed for such equipment are rigid and fixed in nature. Stainless steel continues to lead the way for mass-production drugs and fixed-system approaches. However, over the last two to three years, SUS has increasingly found application in commercial manufacturing.

The biopharmaceutical market has expanded at a high CAGR of 8.4%, vis-à-vis chemically synthesized drugs, as biopharmaceutical drugs form a large share of approvals every year. As a result, specialty drugs have witnessed radical growth, compared with the conventional blockbuster drug model in the mainstream market, suggesting the drug pipeline is slowly transitioning toward targeted therapies. Traditionally, large stainless steel equipment requires costly capital investment, and the installation of large equipment cannot be justified with the manufacturing of biologics.

Growing trend of SUS adoption across CMOs and biotech firms

Smaller and less-funded companies, even contract manufacturing organizations (CMOs), are increasingly opting for single-use equipment in their biomanufacturing processes as it is more efficient and cost-effective. As per our estimates, the global SUS market is poised to grow at a robust rate of 18.8% toward the end of 2021.

According to key suppliers of a wide range of medical equipment, such as GE Healthcare’s Life Sciences division, the share of single-use technologies in new installations stands anywhere between 25% and 50%. CMOs, which manufacture biologics on behalf of larger biopharmaceutical manufacturers, are building small economical facilities with several 2000L single-use bioreactors instead of large stainless steel bioreactors, a trend that was common among leading players 20 years ago. Interestingly, CMOs and smaller / less-funded pharma and biotech companies have a history of employing single-use systems, and are more likely to adopt newer technologies and invest in them. It makes sense for larger biopharmaceutical manufacturers with an existing stainless steel setup to refrain from investing in new SUS facilities due to an expensive installed stainless steel base.

Significant CAPEX reduction and validation of equipment

Contrary to industry perception, single-use manufacturing technologies can help reduce CAPEX cost by up to 50%, and water and energy use by up to 80%, compared with setting up a traditional facility with stainless steel equipment. Our analysis suggests that companies are able to save substantially on manual labor, associated with cleaning stainless steel tanks and bioreactors after each manufacturing process.

Single-use systems eliminate the cleaning process entirely, saving not only on cost associated with manual labor but also on the time required to validate the stainless steel equipment prior to re-use. Traditionally, and even with the current scale of stainless steel systems, a sterile-fluid transfer is carried out through product piping, stainless steel vessels, routing manifolds, and valves, which require cleaning and sterilization before they can be re-used. Being disposable in nature, SUS systems do not require cleaning cycles. Moreover, as per guidelines issued by regulatory authorities, validating disposable single-use equipment takes considerably less time than validating stainless steel equipment.

Extractability and leachability (E&L) continue to raise concerns

Single-use technologies have had their share of negative commotion since inception. Numerous manufacturers do not prefer to invest in single-use manufacturing facilities due to the traditional drawback of extractability and leachability (E&L) concerns with disposable materials. A decade ago, biopharma manufacturers faced the issue of contamination as single-use plastics would leach and destroy a whole batch of biologics in production, costing companies tens of thousands of dollars. However, the scenario today has changed: major manufacturers and suppliers of disposable single-use equipment conduct E&L studies prior to supplying inventory to biopharmaceutical manufacturers. That said, evaluating E&L still remains a pre-requisite errand that biopharma and biotech companies prefer to undertake prior to proceeding with the production of biologics.

The road ahead

As single-use technology gains ground, SUS equipment manufacturers such as Pall, Sartorius, and GE have turned integrators that perform E&L testing on behalf of biopharma manufacturers. As there are no specific regulatory requirements for the E&L testing of single-use equipment, integrators follow certain protocols for E&L testing, as specified by the BioPhorum Operations Group (BPOG).

Thus, with low capital investment owing to reduction in utility requirements, downsizing of the cleanroom area, and decline in overall facility footprint, a single-use facility can be set up in a span of 12–14 months. Since the product flow path is discarded and replaced after each batch, the risk of product cross-contamination between batches is virtually eliminated using SUS, thus making it more suited to small-scale production (up to 2000L). Although the issue of the sustainability of disposing plastics after a single use is likely to raise a few concerns in certain parts of the world, the technology is, no less, more sustainable than stainless steel technology.