Product Characterization

Special Report: Current Analytical Approaches to Biophysical Characterization in a Regulatory Environment

Biologics continue to increase in importance as therapeutics products. In 2018, 12 monoclonal antibodies (MAbs) were awarded first approval in either the European Union or the United States, and some experts forecast that another 12 are set to enter regulatory review in 2019 (1). Development of antibody therapies, peptides, proteins, and more complex product classes (e.g., antibody–drug conjugates, bispecific monoclonal antibodies, and Fc-fusion proteins) are currently being developed to address a wide range of diseases and conditions, including cancer and…

Biosimilarity Assessments: The Totality of Evidence Framework

Biosimilars are evaluated through comparisons with their reference products using abbreviated pathways that have evolved significantly over the past few years. Scientists and regulators now accept that some quality attributes can vary from batch to batch over a product’s lifecycle, even for reference products. Moreover, reference and similar biotechnology products can show differences in noncritical quality attributes but still demonstrate comparable efficacy and safety (1). Here we describe a similarity assessment approach that is also applicable to comparability of lifecycle…

Biopharmaceutical Characterization, Part 2: Applications and Strategies for Diverse Products — A Conference Report

Last fall, KNect365 brought together more than 250 analytical specialists to discuss biological assays and characterization of well-characterized biologics in Rockville, MD. Speakers from the US Food and Drug Administration joined experts from leading biopharmaceutical companies, service providers, and consultancies for case studies, regulatory interactions, sharing perspectives, and learning about emerging technologies. Part 1 of this report in January 2019 focused on the bioassay section of the meeting. Here in Part 2 sponsored by Sartorius, BPI’s senior technical editor reports…

Analytical Challenges: Characterization of Oligonucleotide Therapeutics

Recent approvals of oligonucleotide therapeutics are a clear signal for optimism for this product class. This is supported by the strength of the current pipeline which has over 180 active oligonucleotide clinical programs in various phases of development. Improvements in analytical technology and know-how have played a key role in enabling suitable characterization and quality control strategies to overcome the difficulties associated with testing these complex molecules. Despite the lack of dedicated regulatory guidelines related to characterization or quality control,…

Analytical Tools to Improve Decision-Making During Product Development

Speed to clinic testing — and then speed to market — are highly significant metrics for companies developing biopharmaceuticals. By increasing the pace of drug development, these companies can reduce costs, obtain revenues early, and establish commanding positions in the market relative to their competitors. High-throughput development tools have contributed much to the acceleration of drug development in recent years. Such technologies enable the testing of many process parameters in parallel. Combining them with multifactorial “design of experiment” (DoE) analysis…

Biosimilars: Challenging the Justifications for Clinical Testing

The Biologics Price Competition and Innovation Act (BPIA) of 2009, describes the need for clinical trials as follows (1): “(cc) a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed and intended to be used and for which licensure is sought for the biological product.” However, all the above studies are left…

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…