Strategies for Regulatory Compliance, Method Validation, and Variability Control

The quantification of subvisible particles is a critical aspect of ensuring the safety, efficacy, and overall quality of pharmaceutical products. These particles may originate from extrinsic sources, e.g., environmental contaminants or manufacturing equipment, or be intrinsic to the formulation itself. Their presence can pose significant risks to patients, including immunogenic responses, infusion-related reactions, or diminished therapeutic efficacy. Consequently, regulatory authorities expect routine monitoring and control of subvisible particulate matter as part of pharmaceutical quality control, with defined acceptance criteria for particle size and concentration.

In some cases, subvisible particles are an inherent part of the product. In these instances, precise characterization of particle size distribution, morphology, and concentration is essential to ensure product consistency, biological performance, and patient safety. Any temporal changes in particle attributes may indicate physical instability or degradation processes, making subvisible particle analysis a sensitive and informative stability-indicating parameter. Accordingly, having a robust and precise analytical method for subvisible particle characterization is critical at all stages of the pharmaceutical product lifecycle, spanning from early development to release of clinical or commercial batches.

In this webinar, we will present a case study highlighting the challenges involved in establishing a precise method for (inherent) subvisible particle analysis and its transition from development in an R&D setting to validation in a GMP-compliant environment. We will discuss regulatory requirements, workflows, and quality considerations involved in moving from R&D to GMP. The case study will highlight sources of result variability—such as the selected analytical method, sample preparation procedures, equipment, operators, or combinations thereof – and offer guidance on how to control these factors and improve method performance.