Particulates or aggregates are a notable challenge for injectables, but there are several methods available to help with identification during formulation and development.
Particulates or aggregates can have a detrimental effect on the efficacy and safety of a biological drug in a number of ways. Aggregation, for example, can lead to, or be a consequence of, misfolded proteins in an inactive state, explains Alex Perieteanu, director, biopharmaceutical services at SGS Agriculture, Food and Life. “This effectively reduces the amount of soluble, active molecule able to perform its intended function,” he says. “Alternatively, even if the molecule remains active, an immune response can result in antibody-mediated neutralization of the protein’s activity or in its bioavailability.”
Certain methods can be employed to identify particulates or aggregates in a biological formulation. Perieteanu states that for insoluble aggregates, it is possible to simply use visual appearance for detection when larger particles have formed. “Light obscuration is employed to determine particle counts in the >2 µm, >5 µm, >10 µm, >25 µm range, and to ensure that requirements for injectables, or ophthalmics are met per United States Pharmacopeia (USP) <787>, USP <788>, or USP <789>,” he adds.
In instances where light obscuration is not feasible due to the extensive formation of bubbles or color, it is more suitable to use microscopic evaluation of sub-visible particles, although, this technique is more labor intensive, Perietenau notes. “Additionally, microflow imaging can look at a similar range of particulate sizes to get more detailed understanding of morphology and distribution,” he says.
If the particulates or aggregates are soluble, it is common practice to use techniques such as sodium dodecyl sulfate-polyacrylamide gel electrophoresis/capillary gel electrophoresis (SDS-PAGE/CGE), size-exclusion chromatography (SEC) using multi-angled light scattering (MALS), and analytical ultracentrifugation, Perieteanu asserts.
VERAXA and Voyager to Create Combined Business for Advancing Pipeline of Next-Gen Cancer Therapies
April 23rd 2025The proposed business combination would create a publicly traded, clinical-stage biopharmaceutical company that will focus on developing a pipeline of next-generation cancer therapies.
Tokyo University of Science Research Team Explores Improved Delivery of Antisense Oligonucleotides
April 18th 2025Using cholesterol-modified oligonucleotides, the research team aims to improve the delivery of antisense nucleotide-based therapies for treating neurodegenerative diseases and brain cancers.
Thermo Fisher Opens Advanced Therapies Collaboration Center in California
April 18th 2025The 6000-square-foot facility will provide cell therapy developers the support they need to transition to CGMP manufacturing, and an expanded footprint of the new center is expected to open in Philadelphia later in 2025.