Aspen Alert

The FDA should be more open and collaborative to unleash a surge in approvals of rare disease drugs, according to a report by the National Academies of Sciences, Engineering, and Medicine. Congress asked the FDA to contract with the National Academies to conduct the study. The brief focused on the flexibilities and mechanisms available to regulators, the use of “supplemental data” in the review process and an assessment of collaboration between the FDA and its European counterpart. That brief has spawned a 300-page report that provides a road map for kick-starting orphan drug innovation. Many of the recommendations relate to transparency and collaboration. The National Academies wants the FDA to strengthen its mechanisms for using input from patients and caregivers throughout the drug development process, including by establishing an approach for advisory committee meetings.

AstraZeneca has shared an early look at the performance of its in-house antibody-drug conjugate (ADC) technology, publishing phase 1 data on candidates that could compete with molecules from AbbVie and Pfizer. The Anglo-Swedish drugmaker is a leading light in the hot ADC space, but its successes to date have come from deals with Daiichi Sankyo, not its own labs. That could change in the future. AstraZeneca has used its in-house linker and topoisomerase I payload technologies to create a set of internal ADCs, including a candidate aimed at B7-H4, called AZD8205, and at folate receptor alpha (FRα), called AZD5335. Both those prospects are in phase 1/2a clinical trials.

A trio of biotech companies sold shares in their initial public offerings late last week, an encouraging sign for a sector whose new entrants have lately struggled. Bicara Therapeutics Inc. expanded its IPO to sell 17.5 million shares at $18 each, at the top of the price range, to raise $315 million, according to a statement. While MBX Biosciences Inc. raised $163.2 million in its enlarged first-time share sale, pricing 10.2 million shares at $16 each, according to a statement. And Zenas BioPharma Inc. raised $224.4 million in its first-time sale that was upsized, according to a statement. The IPOs are tasked with wiping the slate clean after a string of lackluster deals in the sector.

Miami Vice burst onto the scene in 1984, a portrait of crime-fighting cool distinguished by trendsetting pastel colors, hot contemporary music and flashy cinematography. The show was an immediate standout for its stylish wardrobe, Italian sports cars and hip attitude — all in contrast to the grim, dangerous work of undercover detectives busting drug cartels and prostitution rings. Don Johnson was the epitome of slick as undercover Det. James “Sonny” Crockett, sporting stubble and residing on a boat with a pet alligator. Philip Michael Thomas played his partner in crimefighting, Det. Ricardo “Rico” Tubbs. Miami Vice ran on NBC from 1984 to 1989, scoring 20 Emmy nominations and winning four Emmys. This year marks the 40th anniversary of its premiere.

For almost a decade, Pamela Barnum worked as an undercover police officer in the drug enforcement unit, where she discovered that absolute power communicates through empathy. In this insightful talk, she shares strategies we can use to courageously connect with others in a way that displays empathy without saying a word. Pamela started her career as an Undercover Police Officer with the Drug Enforcement Division. When she graduated from law school, she left policing and accepted a position as a federal prosecuting attorney. She spent countless hours in the courtroom, perfecting her proficiency as a trust strategist and body language expert.

Compared to other protein therapeutics, there is currently limited knowledge about the residual host cell proteins (HCPs) in adeno-associated virus (AAV)-based gene therapy products. In this study, we have developed a novel workflow for robust and in-depth HCP analysis of AAV samples by combining wide-window data-dependent acquisition for improved low-abundance HCP detection with single-pot, solid-phase-enhanced sample preparation (SP3) for low-input sample preparation. Using this newly developed method, we were able to detect more than 650 HCPs in a commercial AAV1 sample with a high quantitative reproducibility. This represents a greater than 5-fold increase in HCP protein identification compared to an in-solution digestion method followed by traditional data-dependent acquisition.

High-cell-density fermentation is a critical aspect of industrial protein production, requiring the selection of an optimal growth medium and carbon source. Pichia pastoris, a methylotrophic yeast, has been established as a widespread recombinant protein expression system in the food and pharmaceutical industries. The primary objective of this work was to create a superior platform for producing alternative proteins thus contributing to future innovation in these sectors. This study compared three wild-type strains, with two of them also analyzed in their diploid versions, using shake flasks and bioreactors. It investigated glucose and glycerol as carbon sources using mCherry as a protein model. Glycerol emerged as the preferred carbon source, resulting in over 40% increase in biomass concentrations compared to glucose across all strains.

Biopharmaceutical manufacturing processes are resource and energy intensive. At the same time, manufacturers are setting ambitious climate action targets and are striving to make their operations more sustainable. In this webinar, we will highlight some of the key factors that drive water, energy and material usage in typical bioprocesses. Process choices and improvements will be evaluated based on metrics like process mass intensity, energy usage and carbon intensity. A case study will be used to demonstrate the effects of process intensification on the efficiency and sustainability of a manufacturing facility. Advanced single-use technologies can enable process simplification, reaching higher recoveries with less inputs, resulting in improved intensity metrics.

This work presents a case study that demonstrates implementation of a hybrid workflow leveraging both computational and experimental High Throughput Screening (HTS) techniques to develop a MMAEX polishing step for a challenging Fc-fusion protein purification process. The Fc-fusion protein displayed a low pI (pI <6.5), high surface hydrophobicity, and high aggregate content (up to 35% in the harvested cell culture fluid). MMAEX development was carried out with material from two different cell lines that exhibited a wide range of high molecular weight (HMW) levels and different HMW distributions. Significant difference in step performance was observed between the different load materials and this was attributed to the difference in feed purity and impurity composition.

Shake flasks are one of the most frequently used bioprocessing vessels. Especially in strain and bioprocess development for screening applications they offer a cost-effective way to achieve the necessary throughputs. However, shake flasks differ significantly from benchtop bioreactors in their design, operation, and size and present black boxes due to a lack of compatible sensor technology.

Lyophilization is a process that is commonly used to increase the stability of drug products, e.g., mRNA vaccines, in pharmaceutical manufacturing. While extensive efforts have been dedicated to shift the pharmaceutical industry towards continuous manufacturing, the majority of industrial scale lyophilization is still being operated in a batch mode. This article proposes the first mechanistic model for a complete continuous lyophilization process, which includes freezing, primary drying, and secondary drying. The state-of-the-art lyophilization technology is considered, in which vials are suspended and moved continuously through the process. The model can describe the evolution of several critical process parameters, namely the product temperature, ice/water fraction, sublimation front position, and concentration of bound water, for the entire lyophilization process.

The FDA should be more open and collaborative to unleash a surge in approvals of rare disease drugs, according to a report by the National Academies of Sciences, Engineering, and Medicine. Congress asked the FDA to contract with the National Academies to conduct the study. The brief focused on the flexibilities and mechanisms available to regulators, the use of “supplemental data” in the review process and an assessment of collaboration between the FDA and its European counterpart. That brief has spawned a 300-page report that provides a road map for kick-starting orphan drug innovation. Many of the recommendations relate to transparency and collaboration. The National Academies wants the FDA to strengthen its mechanisms for using input from patients and caregivers throughout the drug development process, including by establishing an approach for advisory committee meetings.

Scientists at Kyoto University’s Institute for Integrated Cell-Material Sciences (WPI-iCeMS) have uncovered new details about how cells manage the distribution of lipids in their cell membrane. These lipids, known as phospholipids, are arranged in a bilayer of membranes, regulating entry and exit of certain molecules to maintain a stable internal environment. The new research, published in Nature Communications, identified protein complexes that play an essential role in this process.

Symbiosis Pharmaceutical Services Ltd has purchased new premises in Stirling, Scotland, UK. Close to its existing manufacturing cleanrooms, testing laboratories, and GMP warehouse facilities in Stirling, the purchase will double the company’s existing footprint to 43,500 sq ft (4,000m2). The new manufacturing facility design includes two new cleanroom-based GMP automated production lines to substantially increase the companies’ total aseptic fill/finish manufacturing capacity. The visual inspection of vials post-production and the labeling processes have also been fully automated.

A U.S. Patent for a “Process for Reducing Subvisible Particles in a Pharmaceutical Formulation” was awarded to Regeneron on August 27th, 2024. The present invention provides a stable protein composition containing a surfactant and having less than 400 subvisible particles of 10 microns or greater diameter per container, or less than 10,000 subvisible particles of 2 microns or greater per container. A method of manufacturing such a stable protein composition is disclosed, which includes a unit of operation that removes or decreases an esterase activity that degrades the surfactant.

Adeno-associated viruses (AAVs) are a widely used vector for recombinant genome delivery into cells, and promising vehicles for novel gene therapies. However, sample characterization represents a major challenge for commercial, large-scale manufacturing of AAV-based gene therapies. Current gold standard AAV characterization methods such as analytical ultracentrifugation (AUC), electron microscopy (EM) or qPCR/ ELISA present drawbacks such as long turnaround times, high sample consumption, need for highly specialized staff or outsourcing. Mass photometry can overcome many of the bottlenecks while providing reliable data aligned with the traditional characterization methods.

In spite of his ability and willingness to work hard for his art on Miami Vice, Don Johnson was not a popular choice with NBC executives. Johnson had already starred in a grand total of four failed pilots up until that point and was not the bankable star that he is today. Instead of Johnson, producers considered Nick Nolte and Jeff Bridges. They were particularly keen to sign Vietnam vet and actor Larry Wilcox on for the role. But what turned out to be a stroke of luck for Johnson turned out to be a devastating blow to Wilcox’s acting career.