[Whitepaper] Strategies for Creating Flexibility in New and Legacy Biomanufacturing Facilities

Whitepaper Summary:

While innovation and market demand have had a phenomenal impact on drug development, the manufacturing side has been somewhat slower in evolving to newer, more flexible and cost-effective technologies. However, there is a definite trend in transitioning legacy facilities and new facilities away from the traditional one product-one facility biomanufacturing model in order to capture market demand and produce multiple products in the same facility. So transformative technologies are being incorporated into new facilities as well as aging/legacy facilities with the goal of maximizing capacity and efficiency and also driving down costs.

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In 2015, customers who had used single-use technologies for 10 years had significant cost benefits: 20-30% reduction in operating costs, 40-50% reduction in capital costs, and 30% reduction in time-to-build as compared to traditional stainless steel technology. [1] The cost benefits come from significantly reduced setup and switchover times providing flexibility for manufacturers to quickly change their product lines. Disposables require less maintenance, sterilization, clean steam, chemicals, and energy. [2]

Another highly cost effective transition that is gradually being implemented for portions of the manufacturing process is the switch from batch to continuous manufacturing. Continuous manufacturing saves money, time and space, with impressive advantages over batch processing. [3] Footprints are estimated to be 40-90 percent smaller, resulting in 20-76 percent lower capital expenditures as compared to batch systems. Other advantages include increased capacity for production, less maintenance and lower energy use. Also, there is less time required for scale-up from clinical to commercial scale production. [2]

A few of the industry leaders who have capitalized on this technology are Genzyme and Bayer with continuous perfusion technology for biologics in the initial phase of upstream processing [2] and Pfizer, with their continuous tablet coating approach [4].

Manufacturers are gaining powerful insight into the details of their production quality and performance through Process Analytical Technology (PAT), which involves real-time or rapid measurements for continuous analysis and control of manufacturing processes. Some of the technologies involved are Near-infrared (near-IR) spectroscopy, Raman spectroscopy, and light scattering. The benefits of PAT are a reduction in errors, faster cycle times, and a reduction in overall costs. The ultimate vision for PAT is to not only track the manufacturing process at each stage, but to provide feedback of critical information for real-time decision-making and adjustment of the manufacturing process. [2]

Predictive modelling through multivariate statistical analysis has the potential to unveil hidden process characteristics and provide new insights into production performance, including the root causes of bottlenecks. The most commonly used analysis involves chemometrics analysis for spectroscopy used in in-line/at-line determination of assay and content uniformity, identification of raw materials and finished products, and in-process blending analysis. [2]

Advanced statistical algorithms are also being used to examine the impact of process fluctuations on product loss and to discover the root causes of bottlenecks. [5] A useful data mining tool using multivariate analysis was developed for rapidly predicting whether increased titers would be a good fit for legacy manufacturing facilities originally designed for lower titers, and for predicting whether bottlenecks will occur. [6] In another case study, using two multivariate techniques, Genentech’s manufacturing facility uncovered some avenues to intervene in the metabolic process of their production scale cell culture, steering it towards higher productivity. [7]

To remain competitive, manufacturers must embrace these and other technologies that will enhance flexibility, increase quality, and drive down costs.

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References

  1. Hernandez, R. Top Trends in Biopharmaceutical Manufacturing: 2015. Available from: http://www.pharmtech.com/top-trends-biopharmaceutical-manufacturing-2015.
  2. Deloitte. Advanced Biopharmaceutical Manufacturing: An Evolution Underway. 2015; Available from: http://www2.deloitte.com/us/en/pages/life-sciences-and-health-care/articles/advanced-biopharmaceutical-manufacturing-paper.html.
  3. Brennan, Z. FDA calls on manufacturers to begin switch from batch to continuous production. 2015; Available from: http://www.in-pharmatechnologist.com/Processing/FDA-calls-on-manufacturers-to-begin-switch-from-batch-to-continuous-production.
  4. Wright, R. Pfizer’s Hybrid Approach To Implementing Continuous Manufacturing Processes. 2013; Available from: http://www.pharmaceuticalonline.com/doc/pfizer-s-hybrid-approach-to-implementing-continuous-manufacturing-processes-0001.
  5. Moore, C. Multivariate Tools for Modern Pharmaceutical Control- FDA perspective. IFPAC Annual Meeting. Jan. 22, 2013. Available from: www.fda.gov/downloads/…/CDER/UCM359262.pdf.
  6. Yang, Y., S.S. Farid, and N.F. Thornhill, Data mining for rapid prediction of facility fit and debottlenecking of biomanufacturing facilities. J Biotechnol, 2014. 179: p. 17-25.
  7. Le, H., et al., Multivariate analysis of cell culture bioprocess data–lactate consumption as process indicator. J Biotechnol, 2012. 162(2-3): p. 210-23.

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