A common framework for integrated and continuous biomanufacturing

Abstract

There is a growing application of integrated and continuous bioprocessing (ICB) for manufacturing recombinant protein therapeutics produced from mammalian cells. At first glance, the newly evolved ICB has created a vast diversity of platforms. A closer inspection reveals convergent evolution: nearly all of the major ICB methods have a common framework that could allow manufacturing across a global ecosystem of manufacturers using simple, yet effective, equipment designs. The framework is capable of supporting the manufacturing of most major biopharmaceutical ICB and legacy processes without major changes in the regulatory license. This article reviews the ICB that are being used, or are soon to be used, in a GMP manufacturing setting for recombinant protein production from mammalian cells. The adaptation of the various ICB modes to the common ICB framework will be discussed, along with the pros and cons of such adaptation. The equipment used in the common framework is generally described. This review is presented in sufficient detail to enable discussions of IBC implementation strategy in biopharmaceutical companies and contract manufacturers, and to provide a road map for vendors equipment design. An example plant built on the common framework will be discussed. The flexibility of the plant is demonstrated with batches as small as 0.5 kg or as large as 500 kg. The yearly output of the plant is as much as 8 tons.

The design basis for the integrated and continuous biomanufacturing framework

“…The high‐level consequences of the common framework ICB are discussed in the accompanying article (Coffman et al, 2020 ). Here we discuss the details of the design to demonstrate the flexibility and productivity of the framework ICB.…”

Bioprocess intensification: A route to efficient and sustainable biocatalytic transformations for the future

“…A broader analysis of new bioprocessing concepts has also been modelled and assessed with respect to economics [252]. Likewise, a very useful common framework was recently published to assist the overall evaluation of novel biomanufacturing options in a combined industry-academic partnership [253]. Finally, short-cut calculations have also been used to assess product recovery options [254], where modelling in detail has been found too time-demanding.…”

Mimicking continuous capture chromatography for virus clearance using a single chromatography column model

“…Continuous chromatography has increasingly been used for clinical manufacturing, due to economic benefits, reduced resin and buffer needs, and fewer waste amounts. [ 1,2 ] Different vendors have developed and provide continuous chromatography systems, for example, Chromacon, Novasep, Sartorius, Cytiva, Lewa, and others. These can be run in simulated moving bed principle, for example, the BioSMB system, or periodic counter‐current mode, for example, Cytiva systems.…”

“…Economic benefits in these systems are achieved by overloading the resin of a first column, with antibody binding to that first column. The effluent or break‐through of that first column, containing residual amounts of antibody is then captured via a 2 nd column [ 1,3,4 ] (example in Figure 1A–E). The effluent, containing residual amounts of antibody is referred to as “spent load” as most of the antibody present has been bound to the 1st column.…”