End‐to‐end continuous bioprocessing: Impact on facility design, cost of goods, and cost of development for monoclonal antibodies

Abstract

This article presents a systematic approach to evaluate the business case for continuous processing that captures trade‐offs between manufacturing and development costs for monoclonal antibodies (mAbs). A decisional tool was built that integrated cost of goods (COG) with the cost of development models and new equipment sizing equations tailored to batch, hybrid, and end‐to‐end continuous processes. The COG analysis predicted that single‐use continuous facilities (sized using a dedicated downstream processing train per bioreactor) offer more significant commercial COG savings over stainless steel batch facilities at annual demands of 100–500 kg (~35%), compared to tonnage demands of 1–3 tons (~±10%) that required multiple parallel continuous trains. Single‐use batch facilities were found to compete with continuous options on COG only at 100 kg/year. For the scenarios where batch and continuous facilities offered similar COG, the analysis identified the windows of operation required to reach different COG savings with thresholds for the perfusion rate, volumetric productivity, and media cost. When considering the project lifecycle cost, the analysis indicated that while end‐to‐end continuous facilities may struggle to compete on development costs, they become more cost‐effective than stainless steel batch facilities when considering the total out‐of‐pocket cost across both drug development and commercial activities.

Towards continuous mAb purification: Clearance of host cell proteins from CHO cell culture harvests via “flow‐through affinity chromatography” using peptide‐based adsorbents

“…In addition, we are exploring the use of inexpensive chromatographic substrates, such as silica, which exhibit robust properties (C. Zhang et al, 2018) while may also substantially reduce the cost of production and make LigaGuard™ adsorbent potentially disposable and single‐use (Schmidt, 2022). For continuous or hybrid manufacturing, we envision that multiple LigaGuard™ columns can be installed in parallel trains, similarly to other membrane‐ and resin‐based chromatographic adsorbents utilized in continuous‐ready processes (Mahal et al, 2021). The incoming process flow can be diverted from an exhausted column to fresh columns without impacting process continuity.…”

Crustacean Waste Biorefinery as a Sustainable Cost-Effective Business Model

“…Considering the base model constructed, the integrated production costs are high enough, at all scales, to provide any positive Return. Considering past reports, the production cost stabilizes as the scale increases mainly because the cost of equipment tends to stabilize and the amount of final products increases, thus increasing the financial Return of the process [34,56]. Moreover, this is emphasized by the increase in the percentage that the contribution of the capital represents in the total production cost (Fig.…”

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

“…For your typical 70 kg patient, these doses would amount to totals of 2.8 g for Regkirona™ and 2.8 g-plus-5.6 g (total, 8.4 g) for the Brii cocktail. At a nominal cost for active pharmaceutical ingredient (API) of approximately US$175/g (average costs for midsized biotech company using early-stage fed-batch manufacturing process; [ 539 ]), the cost of goods (COGs) on a per gram basis for API for a single dose would likely exceed US$490 and US$1,470, respectively, for these antibodies. Certainly, if the API costs are lowered due to efficiencies in manufacturing, these costs can be reduced significantly.…”