Regulatory Challenges of Novel Pharmaceutical Excipients: A Review

Abstract

Modern drug delivery systems depend heavily on pharmaceutical excipients, which are fundamental to critical quality attributes (CQAs) like bioavailability, stability, and targeted release profiles. Historical regulatory inertia continues to impede the commercial adoption of novel excipients, despite rapid progress in complex drug modalities, such as biologics, mRNA-lipid nanoparticles, and targeted localized delivery systems. Traditionally, excipients are not reviewed independently but rather approved as part of a final New Drug Application (NDA) or Abbreviated New Drug Application (ANDA). This exposes excipient innovators and drug developers to significant clinical, financial and regulatory risk.

This comprehensive review describes the existing regulatory framework for novel excipients. In this paper, we review the United States Food and Drug Administration (FDA) Novel Excipient Review Pilot Program framework and initial results, describe the integration of novel excipients into the International Council for Harmonization (ICH) Q8, Q9 and Q10 Quality by Design (QbD) lifecycles, and provide a comprehensive analysis of non-clinical toxicology requirements. Finally, this article examines the barriers to adoption by the industry and presents systemic, harmonized frameworks to lower the risk and to speed up the deployment of next-generation functional materials in drug product development.

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Zeinab Al-Tal, Mai Khanfar, Noor Baniali, Athar Tahat, Regulatory Challenges of Novel Pharmaceutical Excipients: A Review, Journal of Drug Delivery Science and Technology, 2026, 108986, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2026.108986.