The single most important biomanufacturing trend in recent years is manufacturing efficiency. Nearly 20 percent of the industry believes that it needs to increase efforts to produce more, do so more quickly, and with fewer resources. This conclusion, drawn from BioPlan Associates’ 14th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, shows the bioprocessing industry continues to express concerns about its ability to optimize operations.
How the industry invests in improvements today will define the strategic direction bioprocessing takes for years to come. In our study, we identified the most important areas in which biomanufacturers expect their suppliers to be focusing their new product development efforts. The top five of 13 “upstream” bioprocessing areas of interest are shown in Exhibit 1. These include single-use devices and continuous bioprocessing innovations. Many of the remaining upstream bioprocessing areas also involved single-use devices as well.
Demands for “downstream” innovations mirror the upstream general areas, and include single-use purification (noted by nearly 36 percent), protein-A alternatives and multiple continuous bioprocessing options. In addition, other, general areas demanded for bioprocessing innovation include ‘“automation, instrumentation” (indicated by nearly 22 percent) and “analytical assays.”
This granularity focused on interest in future innovation and provides a clear perspective of the factors driving needs for overall productivity and efficiency. These are the factors most likely to provide the forward momentum the industry needs to improve efficiency and meet its productivity goals.
The major factors that will continue to advance biopharmaceutical manufacturing efficiency include continuous bioprocessing and single-use systems implementation and integration. Implementing such manufacturing changes tend to require long-term strategic decisions. In a regulated environment, such changes are not done quickly, and introduction of new innovations is not straightforward in this industry due to regulatory issues and long product development time. Regardless, biomanufacturers are willing to pay for innovation to remain competitive, resulting in a continued demand for better ways to cut down time to market and streamlining the overall bioprocessing.
The migration toward continuous bioprocessing has been a natural progression following other major manufacturing industries like chemical and steel. Traditionally, the industry has operated using batch processing modalities where operations are segregated spatially and temporally. Operating in this way for decades, the bioprocessing industry has relied on capital and operational expenditure to allow for growth and improvements while not significantly changing the process methodology.
In our report, 26.5 percent of respondents stated that the top new product development area of interest for biomanufacturers and CMOs is continuous bioprocessing-upstream, but 33.8 percent noted they need continuous downstream innovation. Continuous bioprocessing remains a key area suppliers are expected to focus their developmental efforts.
Continuous processing is also a logical next step for biopharmaceutical manufacturing. It reduces facility downtime, overall costs, equipment size, raw material need and the overall timeline. While continuous processing may not always make sense very early in a product’s development, it can become more attractive once the long-term success of the product and demand for further manufacturing are known.
Implementation of perfusion technologies, which has been limited due to the overall complexity, has begun to pave the way for continuous processing in upstream manufacturing. The early adopters of continuous processing tend to be those who have experience with perfusion technology. These manufacturers have worked through some of the complexities. Recently, continuous processing is becoming more attractive due to the reduction in processing costs and the reduced scale needed. This is particularly attractive where smaller bioreactors and smaller downstream equipment are all that is needed.
One of the key challenges of continuous processing is the assurance that material removed from the bioreactor at different times is of consistent quality. Companies with experience in perfusion technology have demonstrated the steady-state capabilities of a perfusion process and the potential of a more homogenous product. This will be achieved through more real time process monitoring like biomass sensors, in-line metabolite analyzers and pCO2 sensors. Further gains in efficiencies will be seen from increased real-time analytical automation.
Looking forward, how the biomanufacturing industry handles downstream continuous processing is where the focus will lie. Perfusion processes have been well established for continuous upstream manufacturing, so the real leap for the industry will happen in downstream processing. While there are several hurdles to jump through, one example is continuous processing of the bioreactor harvest across the capture step. Reduction of harvest hold time will help reduce a major area of concern for product instability from chemical, physical or enzymatic degradation. It would also increase efficiencies as it simply reduces overall processing time.