The design basis for the integrated and continuous biomanufacturing framework

Abstract

An 8 ton per year manufacturing facility is described based on the framework for integrated and continuous bioprocessing (ICB) common to all known biopharmaceutical implementations. While the output of this plant rivals some of the largest fed‐batch plants in the world, the equipment inside the plant is relatively small: the plant consists of four 2000 L single‐use bioreactors and has a maximum flow rate of 13 L/min. The equipment and facility for the ICB framework is described in sufficient detail to allow biopharmaceutical companies, vendors, contract manufacturers to build or buy their own systems. The design will allow the creation of a global ICB ecosystem that will transform biopharmaceutical manufacturing. The design is fully backward compatible with legacy fed‐batch processes. A clinical production scale is described that can produce smaller batch sizes with the same equipment as that used at the commercial scale. The design described allows the production of as little as 10 g to nearly 35 kg of drug substance per day.

An innovative strategy to recycle permeate in biologics continuous manufacturing process to improve material efficiency and sustainability

“…Media concentrates are often used in large scale perfusion cultures to reduce operational footprint where media is delivered to bioreactors by in‐line dilution of media concentrate and WFI with minor amounts of additional feeds 2 . Using media concentrates provides the opportunity to introduce recycled permeate without causing nutrient dilution effects.…”

“…Perfusion processes for biologics manufacturing provide many benefits over traditional fed‐batch operations. Intensified perfusion cultures can achieve far higher volumetric productivities compared to typical fed‐batch cultures 1,2 . As a result, continuous processes are more economical, and they enhance supply chain agility by allowing use of smaller footprint facilities compared to batch operations for the same overall mass output 3 .…”

A common framework for integrated and continuous biomanufacturing

“…This plant can produce 500 kg batches in 20 days and up to 8 tons per year. The capacity is limited by the solution and media preparation and storage, and, to a lesser extent, the maximum flow rate of the pumps for the capture step (Coffman et al, 2020). The plant can operate either the 500 L or the 2000 L SUB as the N‐stage production bioreactor to allow legacy production.…”

“…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).…”

“…framework plant can expand by adding three more 500 L bioreactors in Stage Two, as well as more media and solution preparation and storage containers shown inFigure 3b, and increased labor. One remarkable feature of the common ICB framework is that the downstream remains unchanged, as discussed in the accompanying article(Coffman et al, 2020). The "numbering up" of bioreactors does not change the regulatory filing.…”