As manufacturers look to reduce carbon footprints and cut costs, Jonathan Royce, GE Healthcare Life Sciences, highlights the economic and environmental advantages of single-use bioprocessing technologies
Worldwide demand for vaccines, insulin and other biopharmaceuticals such as antibodies to treat cancer, arthritis and diabetes, is increasing dramatically, driven by the global ageing population, rising obesity levels and the global effort to reduce the incidence of vaccine-preventable diseases. The global market for biotherapeutics was valued at US$95bn (€72bn) in 2008 and it was projected to grow at a compound annual growth rate (CAGR) of 8.2% to reach $160bn (€121bn) in 2013.1 According to the latest independent figures2, global sales of human and animal vaccines were approximately $25.2bn (€19bn) in 2009, and the market is expected to rise at a CAGR of 17.9% to reach $64.2bn (€45.6bn) by 2015.
Disposables first moved into biopharmaceutical production facilities through the introduction of pleated membrane filter capsules in a sealed plastic housing; then disposable media and buffer bags came on the scene. More recently single-use bioreactors and accessories for cell culture, separation and purification, fluid management and connectivity, as well as prepacked, disposable chromatography columns and other chromatography solutions have come to the fore. An ever-increasing range of single-use technologies and equipment is becoming available for upstream and downstream processing, enabling biomanufacturers to integrate individual unit operations, or complete end-to-end processes, known as ‘plug-and-play’, in a single-use format.
facility design cost
Most of the current biomanufacturing facilities, especially for legacy drugs, are dedicated, stainless steel, hard-piped, large footprint production facilities that typically cost $100–700m (€76–530m) and can take between three and five years to build and validate for a single product. The time required to develop new manufacturing capacity requires enormous investment during the early riskier stages of a drug’s development, where clinical hurdles that delay or prevent product launch place a huge financial burden on drug companies. Furthermore, this contributes to a high cost of goods. For example, in older monoclonal antibody processes, industry figures estimate that as much as 70% of the cost of these products can be attributed to the depreciation on the infrastructure capital investment and the fixed costs required to maintain it.
Disposable modules result in lower operating costs due to reduced utility, labour and chemical costs
In contrast, single-use systems have a huge impact on how these production processes are designed, including how process engineers scale from bench-top to pilot scale and beyond. Recent studies indicate that not only are disposable modules an economical up-front investment cost, but they also result in lower overall operating costs due to reduced utility, labour and raw material (i.e. chemical) costs.
They also have a much shorter lead time than their fixed, stainless steel counterparts, thus reducing time-to-market and allowing companies to enter the revenue-generating stage much more quickly. Therefore, cost benefit can best be attained if the manufacturing facility is as small as feasible and the fixed cost part of production has been reduced at the facility-design stage. Typically, manufacturing costs can be reduced by 20–30% in a well-designed facility based on single-use technology and batch throughput can be 20–30% higher than in a corresponding conventional facility.
greater flexibility
While in the past successful biomanufacturing was based on capacity and the ability to invest in dedicated facilities, the future will be based on flexibility as more products are approved. Some of these, such as the biosimiliars, will be in huge demand, particularly in developing countries, and increasingly it is expected that there will be a shift to more niche markets such as unmet needs in rare diseases or personalised targeted treatments, requiring therapeutic manufacture on a smaller scale.
One of the biggest advantages of single-use systems is flexibility; most importantly, a cleanroom environment can be quickly adapted to suit any process by assembling the required disposable modules in the optimal configuration, thereby accelerating process development by testing different components in a ‘plug-and-play’ approach. The ability to build processing infrastructure from pre-validated components is fast becoming a reality. This supports the growing desire of governments around the world to be self-sufficient on a national level in key bio-pharmaceuticals and have the capability to develop and manufacture vaccines locally. This approach to vaccine manufacture also gives the flexibility to respond rapidly on a regional level to both natural pandemics and bioterrorism.
Production can be scaled up simply by swapping to a larger module or combining batches from several smaller modules in parallel, and exhausted modules can be replaced quickly without interrupting the rest of the process. From a safety perspective, this approach has the advantage that biomanufacturers are not opening systems that have held active biological or cleaning and/or sanitising agents.
With single-use systems there is no cleaning or sterilisation and no validation of cleaning routines
The flexibility afforded by disposables also supports the trend towards multi-product facilities, i.e. the production of different drugs using the same facility, with minimum time and cost, without affecting quality. In these facilities the main bottleneck is the line clearance and validation of cleaning to ensure there is no carry-over of product from earlier batches. With single-use systems, which are delivered preconditioned, there is no cleaning or sterilisation, no validation of cleaning routines, and no process downtime while the equipment is cleaned in place.
Overall, measuring the benefits that flexibility affords a bio-manufacturer is often under-estimated as it can give additional cash flow by optimising use of plant capacity and human capital. It can also affect the productivity of the biomanufacturing plant in the future by enabling the option to take in multiple products in the same facility. From a regulatory point of view there is a significant impact on documentation as cleaning validation is eliminated, therefore less documentation is required. A reduction in the handling of paperwork also reduces the need for training and helps minimise errors.
environmental impact
Single-use systems based on ready-to-use technologies can have a major impact on the environment by reducing energy, water and resource consumption. GE Healthcare conducted a streamlined life cycle environmental study comparing a 500L single-use bioreactor with a traditional 500L stainless steel version at Yale University. The data suggested there is the potential to decrease environmental impact with a single-use bioreactor (WAVE Bioreactor). Using information from a third party company (Green Order, UK) that validates environ-mental claims, it was shown that the single-use bioreactor used 43% less energy and saved around 66,000 litres of water a year. In addition to this positive environmental impact, a saving of 1,300 hours of turnaround time was also achieved, resulting in greater productivity and a significant economic benefit.
Subsequently, a ‘cradle to grave’ life cycle assessment of an entire monoclonal antibody (MAb) process model was conducted. The study was carried out at three capacities (100L, 500L and 2,000L) and consisted of disposable and single-use components from the beginning of the process through to the final fill and finish. Eighteen different parameters were measured that affected health, toxicity, ozone, metals and fossil depletion as well as climate change as measured in CO2. The data demonstrated that single-use components had a measurably positive impact on all categories.
Many countries have limited capabilities for the manufacture of these products, resulting in considerable unmet health needs. The introduction of local ‘in country-for country’ flexible manufacturing capabilities would help overcome this critical health gap.
Single-use technologies are having a transformative influence on the development and production of biopharmaceuticals worldwide. With an increasing prevalence in bio-manufacturing, single-use technologies potentially allow for shorter implementation and changeover times, smaller initial investments, and increased flexibility. This approach provides for great scope in increasing facility utilisation particularly during multi-product manufacture. Furthermore, combining single-use technology with modular design or plug-and-play provides disposable manufacturing solutions that drive speed of response and economics of manufacturing as well as contributing towards environmental sustainability.
GE Healthcare’s ReadyToRock road tour gives scientists and engineers across Europe and North America opportunity to experience a complete suite of flexible, single-use products configured for vaccine or MAb production. For further information visit www.readytorockeu.com
References
1. BCC Research Protein Drugs: Global Markets and Manufacturing, 2008, www.bccresearch.com/report/protein-drugs-markets-manufacturing-bio021c.html
2. BCC Research Vaccine Technologies and Global Markets, 2010, www.bccresearch.com/report/vaccine-technologies-markets-phm014c.html
