Biopharmaceuticals continue to grow in importance and number as pharmaceutical research uncovers new treatment options for new and existing conditions. Growth in emerging economies with improved living standards and a rapidly growing middle class is also helping to fuel this transition. Although the overall pharmaceuticals market is expected to grow at a compounded annual growth rate (CAGR) of 4%-7% to reach $1.3 trillion in 2018,1 significant challenges still exist in the market, including patent cliffs that are already impacting legacy products, mounting and changing regulations, increasingly complicated development and manufacturing processes for in-demand drugs (mainly biologics), and instability in the emerging markets.
Due to the unique aseptic requirements for biopharmaceutical drugs — requirements further compounded by most biologic drugs currently requiring parenteral administration — the manufacturing process is complex, challenging and inexorably linked to the therapeutic and commercial success of biologic products. For the biopharmaceutical industry, both outsourcing partners and technological advancements are proving valuable in overcoming these challenges.
Most notably, single-use systems (SUSs) are offering flexible options for producers looking to drive efficiencies into the biopharmaceutical process. With options for both upstream and downstream processes, the flexible factory concept is becoming the model for cost-effective, aseptic production, whether companies are pursuing major or emerging markets and improved agility with both smalland large-scale production.
Flexibility from Start to Fill-Finish
In the 2015 Nice Insight Equipment Survey (overall n=560, biotechnology n=208), 91% of respondents claimed to be using bioprocessing equipment. The same survey also indicated that quality and performance were by far the most important factors considered when selecting an equipment supplier.2 Though many biopharmaceutical manufacturers have implemented SUSs at various phases of the production cycle, the decision to transition away from more traditional multi-use/stainless steel systems is significant at every level of implementation.
Nice Insight’s 2016 CDMO Outsourcing Survey showed that 50% of those responding outsourced services for sterile/contained manufacturing and 44% outsourced for parenteral manufacturing/packaging, both key to bioprocessing. With that, 55% of respondents outsource to CDMOs for mammalian cell line-based development and biomanufacturing.3 As many current SUSs are designed primarily for mammalian cell cultivation, CDMOs are often some of the earliest adopters of technologies like SUSs. Single-use technology development continues to improve, and solutions now exist for nearly all upstream and downstream processes at most production volumes. These specific benefits include ease of use, increased capacity and an overall reduction in downtime; however, manufacturers with large production volumes of one specific drug may not experience these benefits.
When in place, SUSs can greatly reduce the need for and frequency of sterilize-in-place (SIP) and cleanin-place (CIP) processes, as well as on-site facilities/ equipment associated with these operations, allowing for rapid changeovers of small- and medium-scale production operations without an increased risk of contamination or a large equipment footprint.5
Without the need for fixed equipment or hard piping, the footprint of SUS-based bioprocessing shrinks, and is made mobile and flexible. Similarly, with consumable components (tubing, bags, etc.), single pieces of equipment can perform multiple operations. Despite the category’s many advancements over the decades, there are still risks and limitations associated with the implementation and use of single-use technology.5
Quality Materials, Vendors
Vendor reliability and material quality are critical to the successful implementation and maintenance of an SUS. Though many upstream processes are lower risk in general, due to most liquids being recoverable media or buffer solutions, quality concerns magnify with downstream processes, such as protein purification, one of the final steps in biomanufacturing. SUS equipment failure at these stages presents a greater risk.4 Components are often delivered sterile/readyto-use and the integrity of items such as bags may be verified at delivery, but the fragility of plastic items greatly increases the risk of damage between delivery and use. Point-of-use testing — via helium integrity or pressure decay — can often help minimize these risks/ failures, but vendor selection and material quality are also critical.4
Lower Risk for Global Operations
Emerging markets (Brazil, Russia, India, China, Mexico and Turkey) are growing more rapidly than developed markets and will account for nearly 50% of absolute growth by 2018,1 but the risks involved with penetrating this space are great. These markets often favor local investment over imports, meaning partnership with a local CDMO may be a more reliable option, but SUSs also make the flexible factory, or single-use facility, concept5 a possibility for companies looking to pursue emerging markets and answer demand for generic versions of biopharmaceuticals. Rapid entry and low financial risk are key to providing competitively priced options. Single-use operations provide the flexibility and mobility required to meet these demands.
As single-use technology continues to improve, offering greater capacity, more durable materials and even greater flexibility, their appeal will only grow for biopharmaceutical processors. To speed entry into new markets, manage supply chain risk and take advantage of advanced processes, CDMOs will remain a viable option to access the advantages of single-use technology production.
References
- Global Outlook for Medicines Through 2018, IMS Institute for Healthcare Informatics, 2014. http://www.imshealth.com/en/thought-leadership/imsinstitute/reports/global-outlook-for-medicines-through-2018.
- The 2015 Nice Insight Equipment Survey. Jan 2015. http://www.niceinsight.com.
- The 2016 Nice Insight Contract Development & Manufacturing Survey. Jan 2016. http://www.niceinsight.com.
- Sherrick, A., “Single-Use Integrity Testing Goes Mobile: Manufacturers adopting point-of-use testing with flexibility and mobility.” Pharmaceutical Manufacturing, Nov 2015. http://www.pharmamanufacturing.com/articles/2015/single-use-integrity-testing-goes-mobile/.
- Cattaruzza, C. and Ribault, S., “Process and Facility Design for a Monoclonal Antibody Facility: Single Use Technology delivers strategic flexibility to EMD Millipore,” Pharmaceutical Manufacturing, Oct 2015. http://www.pharmamanufacturing.com/articles/2015/process-facility-design-monoclonalantibody-facility/?show=all.