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What is bioproduction?
Bioproduction is the process by which biopharmaceuticals are fermented, purified and finally packaged and distributed to the end customer. The promise of bioengineering to improve millions of lives will require efficient production and supply chain logistics systems that can manufacture and deliver millions of high quality, low cost products to patients.
The Center for Biopharmaceutical Operations studies ways in which industrial engineering and operations research (IEOR) tools for designing such systems can be applied to biomanufacturing, and to establish a research agenda so that current IEOR tools can be modified, and new tools can be developed, to improve bioproduction systems efficiency.
Goals of the Center for Biopharmaceutical Operations
To develop a fundamental understanding of biomanufacturing by exploring how differences in production scalability, cross-contamination, regulation, and the therapeutic characteristics of biologics impact production planning, capacity expansion planning and analysis, quality control, supply chain optimization, production economics, and organization structure.
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Issues in the Biotechnology Supply Chain
Within other high-tech industries, IEOR tools such as simulation, scheduling and production control, capacity planning and production economics, quality control, and supply chain optimization have helped to dramatically increase efficiency. The potential exists to impact the biopharmaceutical industry in the same way. However, this is a very different industry, with its own set of criteria, constraints, and issues that must be understood and quantified.
Biotechnology supply chain challenges
The biopharmaceutical supply chain represents a unique production challenge, because the technology base for protein manufacture is relatively recent. Large-scale biotechnology manufacture (‘bioproduction’) requires exceptionally stringent levels of cleanliness, quality control mechanisms that actively track hundreds of process parameters, and the ability to control all of these parameters with an imperfect knowledge of the response of the target biological material. These challenges are faced to some degree by the silicon chip manufacture industry, which also requires class-A clean room facilities for production - and which IEOR has considerable experience in. However, the nature of biotechnology fermentation process provides a fertile environment for impurities to grow, which can either lower final drug potency or contaminate batches. Up to 30% of batches in some plants undergo additional testing throughout the production process in order to ensure final product quality.
Biotechnology - a new frontier
In addition, many of the processes by which biological products are produced are not well understood and, as a result, products are often highly variable in output quality. Continuous process improvement throughout the lifecycle of the product is necessary in order to produce consistent material in sufficient quantities. One author notes that the number of pending products for monoclonal antibody drugs (a subset of biotechnology pharmaceuticals) alone will stretch current and projected manufacturing capacities. As such there is a strong need for process improvement to deliver higher yields and lower cycle times, thus generating more product throughput. At prices as high as $4000 per milligram of final product (200 times the price of gold), there is considerable incentive for biotechnology companies to improve processes.
The role and scope of regulation
However, the nascent nature of recombinant technologies and the gravity of current treatment targets for chronic and life-threatening illnesses, such as hemophilia and diabetes, leads to stringent regulation. The key difficulty in large-scale manufacture of protein-based pharmaceuticals continues to be the production of sufficient quantities of the target protein at very low levels of contamination. As such, the Food and Drug Administration (FDA) and Overseas regulatory authorities typically require licensure of the entire process surrounding the production of biotechnology products. This means that any changes to plant or process design must be certified in each country in which it is sold, a process which may take up to 3 years for major projects.
Shortened response time to manufacture
Finally, the competition-free life for drugs is shortening from five to one or two years in some cases. Drug companies recoup the majority of their investments during the short period of patent protection. Thus, drug companies would clearly benefit from the faster scale-up of production facilities once a drug is licensed. Most facilities in existence are currently multi-use as basic site infrastructure allows for the manufacture of a range of product. At least in principle, this means that new drugs can quickly be produced in existing facilities. In practice, however, it is quite difficult for facilities to change production modes because of the sensitivity of culture growth and purification to hundreds of production parameters, including the specifications of the certification process. Thus, it is important to identify major barriers to process certification and to track process certification as an inherent part of the manufacturing process. These key obstacles not addressed by the current literature in the process optimization industry.
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Read more at Bioproduction Group (Bio-G). |
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