Nonantibody Biologics

eBook: MSC-Derived Extracellular Vesicles Challenges in Production, Scale-Up, and Characterization

The discovery of extracellular vesicles (EVs) as an intercellular communication medium has led to explorations of their therapeutic potential. EVs constitute a heterogeneous mixture of several different vesicle populations that may be similar in size but different in content, or vice versa. The vesicles can contain RNAs and proteins as well as DNAs and lipids as biological cargoes. Those cargoes can exist either intraluminally within EVs or on their surface, adding complexity to analytical considerations. EVs are classified into subpopulations…

Building a Comprehensive Toolbox for Oligonucleotide Drug Discovery

Dave Madge, vice president, WuXi AppTec. Dave Madge oversees a number of WuXi AppTec’s preclinical discovery services from his base in Cambridge, UK. He spoke about his company’s capabilities in building new modalities, in particular for oligonucleotide therapeutics. Following an introduction on new modalities and oligonucleotides, he presented a workflow for discovery, chemistry, and biology for siRNA therapeutics, focusing on synthetic DNA and RNA therapeutics. Two main factors contribute to the importance of alternative modalities. First, within the small-molecule and…

Improvements and Innovations in Lentiviral Manufacture

Ryan Cawood, chief scientific officer, WuXi Advanced Therapies. In this presentation, Cawood focused on transient lentiviral manufacturing, plasmid creation and analysis, and stable cell-line development for continuous lentiviral production. The work is performed at WuXi Advanced Therapies facilities in Philadelphia, PA, based on methods developed at the company’s research institute in Oxford, UK. The latter site was Oxgene, a company that Cawood founded and that was acquired by WuXi Advanced Therapies in 2021. The WuXi Advanced Therapies transient lentiviral manufacturing…

Development of a Universal Preparative Anion-Exchange Method to Purify Oligonucleotides

Oligonucleotide-based therapeutics have been studied over recent decades, and their promise as a new drug modality is now being realized. The growing interest in oligonucleotides is driven by their high potential for treating different medical conditions, the growing number of oligonucleotide drugs approved by the US Food and Drug Administration (FDA), an increased focus on personalized medicines, the development of therapies for rare diseases, and the wide adoption of nucleotide-based COVID-19 vaccines. Oligonucleotides are short, linear sequences of DNA or…

eBook: mRNA — Revisiting a Technology That Has Rocketed into Success

At the end of 2018, BPI published its first eBook about mRNA drug products — and quite a lot has happened since then! Our initial report highlighted companies working on mRNA therapeutics for cystic fibrosis, heart disease, and cancer, as well as vaccines. The latter approach took off in 2020 with the advent of SARS-CoV-2 and the COVID-19 pandemic, and in a stunningly short time, the biopharmaceutical industry has learned much about manufacture, formulation, product design, and distribution of mRNA…

SARS-CoV-2 Hyper-Immunoglobulin: Purification and Characterization from Human Convalescent Plasma

The novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) emerged as a major pandemic coronavirus disease in 2019 (COVID-19) and since then has killed many people and paralyzed the global economy (1, 2). With specific antiviral therapeutic agents or antibodies yet to be approved, other antivirals and novel vaccine strategies have been essential to containing the virus and disease transmission. Passive antibody therapy can be used to limit the scope of epidemics by providing patients with antibodies that recognize…

Ask the Expert: Developing Strategic Analytical Programs for Therapeutic Peptides

Ashleigh Wake began her 15 October 2020 “Ask the Expert” presentation by pointing out that peptide products are manufactured in a “regulatory vacuum.” Peptide-product developers must be strategic in designing characterization and quality control (QC) programs. Wake reviewed available methods and explored key considerations for developing phase-appropriate analytical controls. Wake’s Presentation Because peptides overlap small- and large-molecule drugs in size, regulatory expectations differ by product size and clinical indication. Thus, analytical programs should be designed around critical quality attributes (CQAs)…

Removing Oligomers of a Recombinant Human Therapeutic Hormone:
Evaluation of Chromatographic Options for Effectiveness

Aggregation is a common cause of protein instability, which renders a biologic product unfit for therapeutic use. Sometimes it is difficult to purify monomeric proteins from oligomers because of similarities in their isoelectric points (pIs). Proteins such as hormones have pI ranges similar to their oligomers and thus can be difficult to separate out using a conventional polishing chromatographic step such as ion exchange. With those pI similarities, removal of oligomers to a considerable extent by ion exchangers can compromise…

A Universal Assay Determination Method for Antisense Oligonucleotides: A New Slope Spectroscopy Method

Antisense oligonucleotides (ASOs) are short, synthetic, single-stranded oligodeoxynucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms. ASO technology has become an important drug discovery platform for most major pharmaceutical companies. To date, six antisense drugs have been approved by regulatory agencies to treat diseases spanning viral infections, hyperlipidemias, and neurological diseases. More than 50 additional ASO drugs are in clinical trials. For an ASO drug product, an assay of its active pharmaceutical ingredient…

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…