Product Characterization

Speeding Characterization of Biologics: Replace Traditional Assay Technologies with Label-Free Quantification and Kinetics

FortéBio’s Octet instruments are an ideal replacement for ELISA, HPLC, and SPR techniques in quantification of antibodies and recombinant proteins and in testing product potency for lot release. Bio-Layer Interferometry (BLI) technology monitors biomolecular interactions in real time to determine affinity, kinetics, and concentration. The plate-based, microfluidics-free format offers users several distinct advantages over other technologies. BLI-based systems can achieve higher throughput, with the flexibility to measure two to 96 samples simultaneously. Lower maintenance requirements and increased ease-of-use further shorten…

Biological Stealth Bombers: Potency, Regulatory, and Bioprocessing Concerns of Antibody–Drug Conjugates

Seven years ago, the US Food and Drug Administration (FDA) approved the first product in a new class of biologics: antibody–drug conjugates (ADCs). The idea for these products already had been hatched a decade earlier when the promising field of antibody research — touting such molecules as “magic bullets” — had faltered, specifically against oncology-related indications. The early crop of anticancer monoclonal antibodies (MAbs) proved to have only limited efficacy, and interest in developing antibodies as therapeutic agents against cancer…

Rational Design of Liquid Protein Formulations: Application of Biophysical Stability Predictors and Descriptors to Reformulate Biotherapeutics

Successful development of liquid biopharmaceutical formulations requires careful assessment of the biophysical properties of the protein in solution, primarily focused on achieving optimal conformational and colloidal stability of the drug-substance molecule (1–11). It also involves extensive stability studies under stressed conditions. Using state-of-the-art biophysical tools for characterization of developed products, those studies are based on key biophysical descriptors and extended particulate characterization methods (subvisible particles in micro- and nano-size range) to deliver a stable product for market with a shelf…

eBook: Bioinks for Bioprinting — Three-Dimensional Printing in Research and Medicine

Three-dimensional (3D) printing is one method of digital biomanufacturing for both basic biological research and translational, clinical applications. The medical field has used it to create such constructions as 3D surgical models for preoperative planning, to assist surgeons in their procedure preparations, which improves postsurgical outcomes. Examples here include generation of cleft-palate models (1), orthopedic applications (2), and cardiovascular surgical planning (3). Other forms of 3D printing for biological applications — such as 3D bioprinting — go beyond such surgical…

Antibody Higher Order Structure Stability: Polymorphism Revealed By Protein Conformational Array

For protein therapeutics and other biologics, the importance of the molecule’s structure to its efficacy and safety is well established (1–5). In particular, their tertiary and quaternary structures play very important roles in product quality and have been monitored extensively in comparability studies (6–12). However, because of both the large molecular size and rotational property of amino acid α carbons, a protein can assume an enormous number of different conformations (13). For antibody-based biologics such as monoclonal antibodies (MAbs), fusion…

Development Approaches to Adenoassociated Virus Production

After many years of development, gene therapy is beginning to deliver on its promises in the clinic, in some cases with spectacular outputs. Those clinical successes also have led to an influx of funding and engagement from large pharmaceutical companies, thereby bringing the required financial support and expertise for late-stage clinical developments and product commercialization. Although many initial studies were confined to small patient groups and focused on a range of rare monogenetic diseases, new approaches to gene editing have…

Advancements in Characterizing Therapeutic Protein Higher-Order Structure

Electrospray-ionization mass spectrometry (ESI-MS) is a well-established tool for biotherapeutic analysis. It draws intact proteins or peptide ions into the vacuum of a mass spectrometer, where the ion mass is measured. Electrospray ion-mobility mass spectrometry (ESI-IMS) introduces ions into a low-pressure gas, where the effects of aerodynamic drag reveal their shape. This technique is just emerging as a valuable tool for characterizing intact proteins, even though for a decade it’s been the basis of a commercially available medical diagnostic test…

Enabling Faster Workflows with Protein Purification Technologies: Improvements in Chromatography and Electrophoresis

Purification of recombinant proteins is a critical step during protein therapeutics development. Protein therapeutics have a number of classifications based on their potential applications, including use as vaccines and diagnostics as well as for enzymatic, regulatory, or targeting activities (1). For all such applications, identifying and verifying protein purity is most important. Whether proteins themselves are therapeutics or the target proteins of interest, effective purification is essential in drug development. Since the introduction of recombinant proteins in the early 1980s,…

Evolving Bioassay Strategies for Therapeutic Antibodies: Essential Information for Proving Biosimilarity

The modern age of biologics began 35 years ago with the approval of Lilly’s Humulin product — a biosynthetic form of human insulin derived from recombinant DNA and microbial cell culture (1). Today, about a quarter (27%) of the drugs approved yearly by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are biopharmaceuticals: primarily monoclonal antibodies (MAbs), but also vaccines, blood products, and (recently), advanced therapies based on genes and cells. A decade ago, the average…

Biological Characterization Using Protein Crystal Measurements

Monoclonal antibodies (MAbs) have become important therapies and are projected to generate US$125 billion in sales by 2020 (1). Given that potential revenue, biopharmaceutical companies are highly motivated to find novel ways to deliver their drug products and extend patent lifetimes. Many such therapies are administered intravenously at low concentration and large volumes (2). Althea’s Crystalomics technology facilitates delivery of traditional biotherapeutics with high concentration, low viscosity, and low volume by arranging a drug’s individual molecules in an ordered crystal…