End‐to‐end collaboration to transform biopharmaceutical development and manufacturing

Abstract

An ambitious 10‐year collaborative program is described to invent, design, demonstrate, and support commercialization of integrated biopharmaceutical manufacturing technology intended to transform the industry. Our goal is to enable improved control, robustness, and security of supply, dramatically reduced capital and operating cost, flexibility to supply an extremely diverse and changing portfolio of products in the face of uncertainty and changing demand, and faster product development and supply chain velocity, with sustainable raw materials, components, and energy use. The program is organized into workstreams focused on end‐to‐end control strategy, equipment flexibility, next generation technology, sustainability, and a physical test bed to evaluate and demonstrate the technologies that are developed. The elements of the program are synergistic. For example, process intensification results in cost reduction as well as increased sustainability. Improved robustness leads to less inventory, which improves costs and supply chain velocity. Flexibility allows more products to be consolidated into fewer factories, reduces the need for new facilities, simplifies the acquisition of additional capacity if needed, and reduces changeover time, which improves cost and velocity. The program incorporates both drug substance and drug product manufacturing, but this paper will focus on the drug substance elements of the program.

The role of Raman spectroscopy in biopharmaceuticals from development to manufacturing

“…In the USA, the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) supports collaboration between pharmaceutical companies and government agencies such as the FDA and National Institutes of Standards and Technology (NIST). Their 10-year roadmap seeks to address manufacturing cost, robustness, improved control, and supply flexibility [ 17 ]. These forums strongly support collaboration, embrace the PAT/QbD framework, and provide practical insight through their guides and papers.…”

Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate

“…The need for innovation in biopharmaceutical manufacturing has been highlighted by the COVID-19 pandemic [1] , as well as, more generally, by the long-term increase in the use and cost of biologic drugs [2] . This has been recognized through regulatory initiatives such as the Advanced Technology Team within FDA [3] and the formation of government-academic-industrial partnerships such as the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) [4] . At the level of process design, the key trends are intensification and flexibility, where intensification refers to increasing efficiency on the basis of cost, space, and/or time [5] , and flexibility refers to processes that are modular, portable from facility to facility, and amenable to changes in production rates [4] .…”

“…This has been recognized through regulatory initiatives such as the Advanced Technology Team within FDA [3] and the formation of government-academic-industrial partnerships such as the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) [4] . At the level of process design, the key trends are intensification and flexibility, where intensification refers to increasing efficiency on the basis of cost, space, and/or time [5] , and flexibility refers to processes that are modular, portable from facility to facility, and amenable to changes in production rates [4] . At the level of technology, some approaches are especially interesting because of their potential to deliver both flexibility and intensification simultaneously.…”

“…At the level of technology, some approaches are especially interesting because of their potential to deliver both flexibility and intensification simultaneously. These include single-use systems [4] , [6] ; alternatives to conventional chromatography that are less equipment- and buffer-intensive [7] , [8] , [9] , [10] ; and the integration of multiple unit operations into more streamlined procedures with smaller footprints, e.g., by combining primary recovery and initial purification using expanded bed adsorption of cell lysates [11] or host cells engineered for selective product release [12] .…”

A common framework for integrated and continuous biomanufacturing

“…We report in a companion article in this issue (Coffman et al, 2020) the design basis for the framework integrated and continuous bioprocess that is sufficiently detailed to allow CMOs and bioprocessing vendors to design plants and equipment that would enable a global ecosystem high productivity manufacturing sufficient to supply mAbs for treating and preventing COVID-19 and other diseases. This framework ICB is being used as the basis for the "first generation" of ICB for The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a US government/academic/ industrial bioprocessing consortium, also co-published in this issue (Erickson et al, 2021).…”