Robust mechanistic modeling of protein ion-exchange chromatography.

Mechanistic models for ion-exchange chromatography of proteins are well-established and a broad consensus exists on most aspects of the detailed mathematical and physical description. A variety of specializations of these models can typically capture the general locations of elution peaks, but discrepancies are often observed in peak position and shape, especially if the column load level is in the non-linear range. These discrepancies may prevent the use of models for high-fidelity predictive applications such as process characterization and development of high-purity and -productivity process steps.

Through Internet and Friends: Translation of Air Pollution Research in Malmö Municipality, Sweden.

Air pollution is estimated to cause more than 7000 deaths annually in Sweden alone. To reduce the impact of air pollution and to plan and build sustainable cities, it is vital that research is translated into efficient decisions and practice. However, how do civil servants in a municipality access research results? How do they normally find relevant information, and what obstacles are there to accessing and applying research results? As part of the collaborative and transdisciplinary research project Air Pollution Research in Local Environmental Planning (ARIEL), these questions were explored through interviews and seminars with civil servants within the Malmö Municipality Environmental Office.

Multi-column displacement chromatography for separation of charge variants of monoclonal antibodies.

Native forms of therapeutic monoclonal antibodies (mAbs) coexist with various acidic and basic charge variants throughout process development and into drug product formulation. During downstream purification, a product's charge variant composition is controlled, as necessary, primarily through peak fractionation and pooling of elution fractions using cation-exchange chromatography (CEX). This can be a cumbersome process with poor resolution and it may result in a significant reduction in product yield.

Harnessing photoinduced electron transfer to optically determine protein sub-nanoscale atomic distances.

Proteins possess a complex and dynamic structure, which is influenced by external signals and may change as they perform their biological functions. We present an optical approach, distance-encoding photoinduced electron transfer (DEPET), capable of the simultaneous study of protein structure and function. An alternative to FRET-based methods, DEPET is based on the quenching of small conjugated fluorophores by photoinduced electron transfer: a reaction that requires contact of the excited fluorophore with a suitable electron donor.

Estimated health benefits of exhaust free transport in the city of Malmö, Southern Sweden.

Air pollution is responsible for one in eight premature deaths worldwide, and thereby a major threat to human health. Health impact assessments of hypothetic changes in air pollution concentrations can be used as a mean of assessing the health impacts of policy, plans and projects, and support decision-makers in choices to prevent disease. The aim of this study was to estimate health impacts attributable to a hypothetical decrease in air pollution concentrations in the city of Malmö in Southern Sweden corresponding to a policy on-road transportations without tail-pipe emissions in the municipality.

Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.

This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures.

Model-based risk analysis of coupled process steps.

A section of a biopharmaceutical manufacturing process involving the enzymatic coupling of a polymer to a therapeutic protein was characterized with regards to the process parameter sensitivity and design space. To minimize the formation of unwanted by-products in the enzymatic reaction, the substrate was added in small amounts and unreacted protein was separated using size-exclusion chromatography (SEC) and recycled to the reactor. The quality of the final recovered product was thus a result of the conditions in both the reactor and the SEC, and a design space had to be established for both processes together.

Pooling control in variable preparative chromatography processes.

Preparative chromatographic columns that run at high loads are highly sensitive to batch-to-batch disturbances of the process parameters, placing high demands on the strategy used for pooling of the product fractions. A new approach to pooling control is presented in a proof-of-concept study. A model-based sensitivity analysis was performed identifying the critical process parameters to product purity and optimal cut points.