Governments and biopharmaceutical organizations aggressively leveraged expeditious communication capabilities, decision models and global strategies to make a COVID-19 vaccine happen within a period of 12 months. This was an unusual effort and cannot be transferred to normal times. However, this focus on a single vaccine has also led to other treatments and drug developments being sidelined. Society expects the pharmaceutical industry to provide an uninterrupted supply of medicines. However, it is often overlooked how complex the manufacture of these compounds is and what logistics are required, not to mention the time needed to develop new drugs. The overarching theme, therefore, is patient access and how we can help ensure access and extend it to low- and middle-income countries. Despite unceasing efforts to make medications available to all patient populations, this must never be done at the expense of patient safety. A major fraction of the costs in biopharmaceutical manufacturing are for drug discovery, process development, and clinical studies. Infrastructure costs are very difficult to quantify because they often depend on whether a greenfield facility or an existing, depreciated facility is used or adapted for a new product. To accelerate process development concepts of platform process and prior knowledge are increasingly leveraged. While more traditional protein therapeutics continue to dominate the field, we are also experiencing the exciting emergence and evolution of other therapeutic formats (bispecifics, tetravalent mAbs, antibody-drug conjugates, enzymes, peptides, etc.) that offer unique treatment options for patients. Protein modalities are still dominant, but new modalities are being developed that can be learned from including advanced therapeutics like cell and gene therapies. The industry must develop a model-based strategy for process development and technologies such as continuous integrated biomanufacturing must be adopted. The overall conclusion is that the pandemic pace was unsustainable, focused on vaccine delivery at the expense of other modalities/disease targets, and had implications for professional and personal life (work-life balance). Routinely reducing development time from 10 years to 1 year is nearly impossible to achieve. Environmental aspects of sustainable downstream processing are also described.

In the manufacture of therapeutic monoclonal antibodies (mAbs), the clarified cell culture fluid is typically loaded onto an initial protein A affinity capture column. Imperfect mass transfer and loading to maximum capacity can risk antibody breakthrough and loss of valuable product, but conservative underloading wastes expensive protein A resin. In addition, the effects of column fouling and ligand degradation require the frequent optimization of IgG loading to avoid wastage. Therefore, continuous real-time monitoring of IgG flowthrough is of great interest. We previously developed a fluorescence-based monitoring technology that allows mix-and-read mAb detection in cell culture fluid. Here we report the use of reporters immobilized on CNBr-activated Sepharose 4B resin for continuous detection of IgG in column breakthrough. The column effluent is continuously contacted with immobilized fluorescein-labeled Fc-binding ligands to produce an immediately detectable change in fluorescence intensity. The technology allows rapid and reliable monitoring of IgG in a flowing stream of clarified cell culture fluid emerging from a Protein A column, without prior sample preparation. We observed a significant change in fluorescence intensity at 0.5 g/L human IgG, sufficient to detect a 5% breakthrough of a 10 g/L load, within 2 minutes at a flow rate of 0.5 mL/min.

Understanding the transport of sediments in urban estuaries and their effects on water quality and microorganisms is a convergent challenge that has yet to be addressed especially as a result of natural hazards that affect the hydrodynamics of estuarine systems. This study provides a holistic view of the longitudinal nature and character of sediment in an urban estuary, the Galveston Bay Estuarine System (GBES), under daily and extreme flow regimes and presents the results of water and sediment sampling after Hurricane Harvey. The sediment sampling quantified total suspended sediment (TSS) concentrations, metal concentrations and the diversity of microbial communities. The results revealed the impact of the substantial sediment loads that were transported into the GBES in terms of the sediment grain type, the spatial distribution of trace metals and the diversity of microbial communities. A measurable shift in the percentage of silt relative to historical norms was noted in the GBES after Hurricane Harvey. Not only did sediment metal data confirm this shift and its ensuing impact on metal concentrations; microbial data provided ample evidence of the effect of leaks and spills from wastewater treatment plants, Superfund Sites and industrial runoff on microbial diversity. The research demonstrates the importance of understanding longitudinal sediment transport and deposition in estuarine systems under daily flow regimes, but more critically, following natural hazard events to ensure sustainability and resilience of systems such as the GBES that encounter numerous acute and chronic stresses.