2020

Microbial Expression and Purification: One Company’s Historical Perspective

Since the dawn of the recombinant DNA era in the 1970s, New England Biolabs (NEB) has been integrally involved in expressing and purifying proteins, both for its own research interests and for biomanufacturing processes. In 1978, the company began screening microorganisms for restriction enzymes. Our scientists remember the challenges met in purifying limited amounts of restriction enzymes and other proteins from native organisms isolated from the environment. The efforts of those scientists to clone, overexpress, and purify restriction enzymes from…

Ask the Expert: Translating Inhaled and Nasal Technologies for Biologics Delivery

Gastric delivery is unachievable for most biopharmaceuticals, so drug developers formulate biologics primarily for intravenous infusion or injection. However, inhaled and nasal delivery options are attracting considerable attention because they enable targeted delivery of a wide range of therapeutic proteins. On 23 June 2020, Mark Parry (technical director at Intertek) presented an “Ask the Expert” webinar that described critical considerations for inhaled and nasal delivery for biologics. Parry’s Presentation Because biopharmaceuticals are complex products, developers need compelling reasons to choose…

Ask the Expert: Ultrapure Gelatin Can Optimize Your Excipient Screening for Vaccine Formulation

In his 28 May 2020 “Ask the Expert” presentation, Jeroen Geeraerts (business development manager at Rousselot) highlighted that, as of May 2020, 118 candidate vaccines for the novel coronavirus (SARS-CoV-2) had reached clinical or preclinical evaluation. Of those, 11 use inactivated and live–attenuated approaches, which require strong stabilizing agents to maintain vaccine potency. Geeraerts explained why inactivated and live–attenuated vaccines require stabilizing agents and why vaccine companies prefer pharmaceutical-grade gelatin for such applications. Next, Geeraerts described how his company’s X-Pure…

Ask the Expert: An Innovative System for Advanced, High-Throughput Aggregate Analysis

Distinguishing aggregated active pharmaceutical ingredients (APIs) from other particle types is critical to evaluating a protein product’s stability, but standard characterization tools struggle to discriminate proteins from nonproteins with similar sizes, shapes, and morphologies. In a 25 June 2020 “Ask the Expert” webcast, Bernardo Cordovez (founder and chief scientific officer of Halo Labs) introduced his company’s Aura subvisible-particle analyzer. He explained how the device combines an innovative microscopy technique with sophisticated imaging software to characterize subvisible particles more quickly and…

Democratizing Access to Cancer-Related Proteomic Data

The US National Cancer Institute (NCI) has launched the Proteomic Data Commons (PDC), a next-generation proteomic data repository that will facilitate data access, sharing, and analysis to speed development of precision-medicine therapies for cancer. Housed within the NCI’s Cancer Research Data Commons (CRDC), PDC hosts several multiomic data sets that have corresponding genomics and imaging data elsewhere, simplifying their access to enable integrative research. Increase Access to Enable Discovery Mass spectrometry (MS)–based proteomic profiling for pancancer analyses could enhance our…

Development of Patient-Focused Commercial Specifications: Understanding Clinical Relevance and Criticality of Quality Attributes

The CASSS chemistry, manufacturing, and controls (CMC) Strategy Forum on 23 January 2019 in Washington, DC, was entitled, “The Development of Patient-Focused Commercial Specifications Through Understanding of Clinical Relevance and Criticality of Quality Attributes.” This forum covered the definition, identification, control, and management of patient-focused attributes throughout the life cycle (from discovery through approval) of biological products, including vaccines. Participants investigated how to differentiate through the product development life cycle which attributes are “clinically meaningful” from those applied for manufacturing…

Dissolved Oxygen Control Tuning for Cell Culture Applications

Proper tuning of dissolved oxygen (DO) controller proportional integral (PI) values is essential for optimal cell culture performance in a bioreactor. When DO-PI values are optimized, gas flows are smoothed, and foaming and cell stress are reduced. Traditionally, this tuning has been performed by using nitrogen gas to purge oxygen from a test solution, thus simulating oxygen demand. That method has several drawbacks, however. First, nitrogen gassing cannot simulate the high demands of high-density fermentation. Second, nitrogen competes with other…

Novel Integrated Raman Spectroscopy Technology for Minibioreactors: Accelerating Raman Model Building for Cell Culture Monitoring and Control

Raman spectroscopy is used widely in biomanufacturing as a process analytical technology (PAT) for monitoring analytes such as glucose and lactate (1). Predictive Raman models also can be used to control glucose concentration in cell cultures (2). The technique is becoming more popular for pilot- and manufacturing-scale bioreactors, but it only recently has been studied with minibioreactors for measuring analytes and producing predictive Raman models for feedback control (3) thanks to advances in integrated technology for automating sampling, analysis, and…

Breaking the Bottlenecks: Accelerating Viral Vector Bioanalysis in Downstream Processing

The rise in popularity of viral-vector–based gene therapies and SARS-CoV-2 vaccines has created a shortage of manufacturing capacity, driving efficiency improvements to avoid bottlenecks in bioanalysis to support culture optimization and bioprocessing steps. To improve workflows in bioanalytical assay development and sample analysis, more efficient methods are needed that include higher throughput, simpler and more streamlined sample assay methods, wide dynamic ranges, and efficient data processing and interpretation. Gyrolab™ microfluidic, nanoliter-scale immunoassay systems provide an innovative, robust solution to high-performance…

Peptide Therapies: Designing a Science-Led Strategic Quality Control Program

Peptide therapeutics are a unique class of pharmaceuticals. They can fall into one or more regulatory categories: as conventional chemical molecules, biological entities, or biosimilars. Developing a well–thought-out quality control (QC) strategy is key to meeting development milestones and complying with evolving regulatory requirements. Safety assessment is critical because slight changes in the structure, physicochemical properties, stability, and impurity profile of a peptide can provoke an adverse immune response. A robust analytical QC program should be conducted in laboratories that…