Uncertainties in Subvisible Particulates Need to Be Understood, FDA Tells Biotech CMC Strategy Forum

The uncertainties around subvisible particles (SVPs) may warrant their being controlled as a critical quality attribute, FDA Office of Biotechnology Products Division of Therapeutic Proteins (DTP) Deputy Director Barry Cherney stressed at a CASSS/FDA CMC Strategy Forum in Washington, D.C in January.

Drawing from the ICH Q8 guidance, Cherney underscored, as a “major point,” the applicability to SVPs of the principle that “if there is a theoretical risk of uncertain significance, in the absence of convincing data that the attribute is not critical, you should assume it is critical and needs to be controlled.”

The January forum – the latest in the series of CMC strategy forums held semiannually in the US on key biotech regulatory concerns – brought industry and agency experts together to discuss “a practical approach to the analysis and immunogenic potential of aggregates and particles.”

The uncertainties that present themselves around the analysis, significance and control of particulates in biotech products have been receiving considerable attention recently, and the CMC strategy forum continued the dialogue that has taken place at industry/regulator venues in the latter half of 2010.

The issues were explored at a session of the AAPS annual meeting in New Orleans in November and at a two and a half-day USP workshop held at its headquarters in Maryland in December. The USP workshop assessed the current science and regulation of particulates in biotech products as well as in aerosols and small molecule injectables and how the pharmacopeia can contribute in the guidance and standard-setting effort.

At the CMC strategy forum, Cherney focused on the “current regulatory considerations for the assessment of subvisible particles” – an area in the particulate debate where the analytical and clinical uncertainties are especially challenging and the science fast-moving.

Cherney offered insights on: ● the knowns and unknowns of SVPs and immunogenicity ● assessing the risks of SVP occurrence and the severity of the consequences ● risk reduction and control strategies, and ● current recommendations.

[Cherney’s insights are provided for subscribers here.  Non-subscribers can purchase the full story for $195 by contacting Karen Bertani (Jonathan@ipq.org).  For subscription information click here.]