Quantitative assessment of environmental impact of biologics manufacturing using process mass intensity analysis

Abstract

Process mass intensity (PMI) is a benchmarking metric to evaluate the efficiency of a manufacturing process, which is indicative of the environmental impact of the process. Although this metric is commonly applied for small molecule manufacturing processes, it is less commonly applied to biologics. In this study, an Excel based tool developed by the ACS GCI Pharmaceutical Roundtable was used to calculate PMI of different manufacturing processes for a monoclonal antibody (mAb). For the upstream process, three different versions were compared: fed‐batch, fed‐batch with N‐1 perfusion, and perfusion in the N‐stage bioreactor. For each upstream process version, an appropriate downstream operational mode was evaluated from the following: a column chromatography process utilizing Protein A and anion exchange (AEX) resin, a Protein A column and an AEX membrane, and a three‐column periodic counter‐current (3C PCC) chromatography process for Protein A and an AEX membrane. The impact of these different process variations on PMI was evaluated. Of all the process inputs, water contributes about 92–94% of the overall PMI. Additionally, the upstream processes and the chromatography steps account for 32–47 and 34–54% of the overall PMI, respectively. Sensitivity analysis was performed to identify opportunities for further reducing PMI. These data indicate that a semicontinuous manufacturing process (perfusion, 3C PCC, and AEX membrane) is the most efficient process, resulting in a 23% reduction of PMI when compared with the fed batch and two‐column chromatography process. Together, PMI can be used to guide the development of efficient and environmentally sustainable mAb manufacturing processes. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1566–1573, 2018

Economic and ecological benefits of a leaky E. coli strain for downstream processing: a case study for staphylococcal protein A

“…4(A)]. 4,5 Furthermore, AEX had the highest fraction of process‐related water consumption, whereas the contribution of all other unit operations to the PMI was due mainly to cleaning water. However, the more efficient AEX capture step in the extracellular process EX entailed the largest PMI savings compared to the intracellular process IN [Fig.…”

“…Apart from the costs, the ecological footprint is an increasingly important factor in the evaluation of recombinant protein production processes. Recently, process mass intensity (PMI) was proposed as a metric to evaluate the resource efficiency of recombinant protein production 4,5 . The PMI relates the mass of consumed raw materials to the mass of produced protein.…”

“…Thus, using the WARIEN and PMI as metrics to assess the sustainability of bioprocesses can reveal potential savings, both in resource consumption and carbon footprint. Furthermore, reducing water utilization lowers costs by downscaling the equipment needed for water preparation and storage 4,5,8 …”

Continuous countercurrent chromatographic twin‐column purification of oligonucleotides: The role of the displacement effect

“…Finally, the process mass intensity (PMI) is also calculated as an index of the overall process efficiency of the manufacturing process, specifically with respect to its environmental impact. This is given by the ratio between the total input mass to the process (buffers, raw material, and resin) (mass process ) and the mass of purified product (Cataldo et al, 2020; Madabhushi et al, 2018), as indicated in Equation (5): $$$\mathrm{PMI}\unicode{x02007}({\rm{g}}/{\rm{g}})=\frac{{m}_{\mathrm{process}}}{{m}_{\mathrm{recovered}}}.$$$…”

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

“…The complexity of achieving carbon‐neutral bioprocessing has been highlighted by initial assessments (Budzinski et al, 2019 ; Pietrzykowski et al, 2013 ). For example, the first process mass intensity analysis showed bioprocesses to be heavily water intensive, where 90% of the mass was from water (Budzinski et al, 2019 ; Madabhushi et al, 2018 ) and 1 g of biological drug requires up to 65 L of water (Jungbauer & Walch, 2015 ). Lifecycle assessment (LCA) studies have demonstrated that single‐use (SU) technologies provide additional environmental impact advantages over the traditional stainless‐steel manufacturing, such as eliminating clean‐in‐place water usage, reducing HVAC energy usage through the use of closed systems and provide smaller footprint processing (Pietrzykowski et al, 2013 ).…”