Check Out Our 2022 Biopharma Coverage

You may have noticed that we’ve been honing in on our four Core Topics – Mass Spec, Chromatography, Spectroscopy, and our only application area: (Bio)pharma – in 2022. Having spent several years working on our sister publication, The Medicine Maker, pharma is a topic close to my heart, and I’ve enjoyed getting to grips with all the ways analytical science is making a difference – from small, to large molecules and even advanced therapies. 

So we thought we’d share some of the pieces we’ve published in the (Bio)pharma space so far this year, including some more recent bioprocessing stories, with quotes from our contributors; news stories and a selection of articles on the analytical challenges – and solutions – in cell and gene therapy.

There will be more pharma content coming over the coming months, so please do let me know if there are particular angles we should be covering. And of course, we’re always open to article pitches. As usual, it’s: [email protected]

Large Molecules

Towards bioprocessing 4.0 
 

Which emerging analytical technologies could make a difference to PAT in bioprocessing? “Raman spectroscopy offers great potential for real-time and in-situ measurement of relevant cell culture CPPs and CQAs,” says Merck’s Stacy Shollenberger. “High-performance liquid chromatography (HPLC) is also a proven tool for CPP/CQA monitoring. Historically, HPLC has been performed in an off-line fashion – a process that can often take days or weeks to complete.” Shollenberger also discusses coupling HPLC with MS to streamlined workflows for biopharmaceutical analysis with a multi-attribute method (MAM). “In addition to the sensor-based and analytical technologies, automated sampling is a key enabling technology for PAT.” Read more!

Collaborating to accelerate bioprocess development
 

Another collaboration here – Waters and Sartorius are working together to accelerate cell line clone selection. We caught up with Waters’ Davy Petit to find out more. “We want to maximize drug product quality, yield, and manufacturing efficiency – all while reducing the development timeline,” he says. “Ultimately, we want to fully integrate process control, monitoring, and product quality testing into the manufacturing environment.” Read more! 

mAb aggregation: knowledge is power
 

Monoclonal antibodies are prone to protein aggregation during production, which can impact efficiency and lead to drug safety concerns for patients. To better understand how protein aggregation occurs – which in turn could improve bioprocessing efficiency and safety – Brandon Ruotolo’s team at the University of Michigan used ion mobility-MS to capture the higher-order structure of mAbs at the millisecond timescale. “The native IM-MS methods we discuss could directly impact the way antibody stress studies are conducted when moved to an automated framework,” says Ruotolo. “Furthermore, the information we’ve gathered so far on mAb aggregation and oligomer structures will likely be useful in the continued development and discovery of next-generation therapeutics.” Read more! 

 mAb Dose Personalization with Bioanalysis
 

Continuing with mAbs, Mohsin El Amrani, Utrecht University, wrote an opinion piece arguing that 2D-LC with HRAM-MS can pave the way for bioanalytical quantification of next-generation therapeutic mAbs. “Though therapeutic proteins offer revolutionary treatment pathways, they must be dosed at correct levels for the patient to achieve maximum effect,” he says. “2D-LC with HRAM-MS provides a sufficiently robust and rapid method for quantifying mAbs. The technique provides a new way to quickly develop a bioanalytical method for quantifying mAbs in plasma, and will become increasingly important as more mAb therapies become humanized.” Read more! 

The trendsetting techniques of biotherapeutic characterization
 

Eliza Lee, Lead Scientist at Samsung Biologics, examines the use and evolution of three key analytical technologies – ELISA, PCR DNA amplification, and capillary electrophoresis – for biotherapeutic molecule characterization. “Industry experience tells us that when manufacturers combine fit-for-purpose cell line development platforms with advanced structural and functional analytical methods, it can optimize development and accelerate project timelines,” she says. “Incorporating phase-appropriate analytical platform methods along with high-throughput techniques to accurately characterize molecules in development will play an increasingly crucial role, helping biologics developers bring safe and efficacious drugs to patients faster.” Read more!

Cell and Gene Therapies

George Buchman on advanced therapy analysis 

“In some ways, we are already living in the future. Diseases such as spinal muscular atrophy (SMA) that were previously not treatable, and terminal by age two, now have a commercial cure available. The field will begin to mature as it did for monoclonal antibody therapies, with improvements in production yields that will correlate with reduced levels of impurities per unit dose, access to treatments and cures to more patients, and decreased costs. And that will lead to new treatments and cures entering the clinic for hundreds of diseases. Out of necessity, the analytics will have to keep up – especially with the need to correlate clinical outcomes with our ability to measure critical quality attributes.” Read more! 

Advanced medicine’s analytical wish list
 

Which analytical techniques could revolutionize cell and gene therapy development? Rakel Lopez de Maturana, Qualified Person & Quality Control Director at VIVEbiotech, reveals her wish list: “There are a number of techniques that could help overcome analytical challenges in ATMP characterization; for example, mass photometry, interferometric light microscopy (ILM), micro-flow imaging (MFI) microscopy, dynamic light scattering (DLS), and multi-angle light scattering (MALS) coupled to separation technologies (size exclusion chromatography [SEC]-MALS, field-flow fractionation [FFF]-MALS) can be used to assess physical titer, full/empty ratios, size, and aggregation or subvisible particle impurities.” Read more! 

Live analytical challenges 
 

A hot topic across biopharmaceutical manufacturing is in-line measurement of critical quality attributes. Here, Dalip Sethi, Director of Scientific Affairs, Terumo BCT, believes we have the tools to make it happen in cell and gene therapy. “Analytical science has a plethora of tools that can potentially be employed to the cell and gene therapy space. For example, Fourier-transform infrared spectroscopy (FT-IR) could potentially enable in-line measurement of metabolic data, such as glucose and lactate values, which are currently measured using off-line or at-line enzyme-based sensors.” Read more! 

Dynamic analytics
 

Continuing with quality monitoring in advanced therapy bioprocesses, researchers from Georgia Institute of Technology, have developed a Dynamic Sampling Platform – an integrated sample-to-analysis system that combines a sampling interface, cell processing device, and detection by nanoelectrospray ionization mass spectrometry (nESI-MS). “The platform has demonstrated the capability to rapidly detect clinically relevant intracellular biomarkers – compounds that were previously identified via conventional HPLC ESI-MS and a long analysis time,” says Andrei Fedorov, one of the researchers. Read more