Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions

Meredith R McGuire; Agm Mostofa; Jihong Shon; Mitchell Frost; Myong-Jin Kim; Karen Li

doi:10.1016/j.ijpharm.2024.124229

Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions

Int J Pharm. 2024 May 16:659:124229. doi: 10.1016/j.ijpharm.2024.124229. Online ahead of print.

Authors

Meredith R McGuire¹, Agm Mostofa¹, Jihong Shon¹, Mitchell Frost¹, Myong-Jin Kim¹, Karen Li²

Affiliations

¹ Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
² Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: karen.li@fda.hhs.gov.

PMID: 38762166
DOI: 10.1016/j.ijpharm.2024.124229

Abstract

The swallowability of solid oral dosage forms (SODFs) is crucial for medication safety and adherence. Both regulatory agencies and sponsors are concerned with bringing swallowable SODFs to patients. However, no best practices are available for assessing swallowability. Therefore, we conducted a comparative analysis of clinical swallowability assessments (CSAs) for SODFs in regulatory submissions to identify current study design practices. CSAs were identified from a "swallowability" keyword search of a Food and Drug Administration database. Notable design trends among the 17 CSAs were not assessing swallowability as a primary endpoint (76 %); enrolling pediatric patients (76 %); administering assessments post-screening (76 %); and utilizing questionnaires (100 %). A design trend with near equal frequency (∼50 %) was single- or multiple-doses of product administration. Study subjects were the primary questionnaire respondents (82 %), usually using a Likert scale (92 %, 12/13). CSAs generally dichotomized the responses for analysis (65 %) without pre-specified threshold values (59 %). Overall, while study designs exhibited trends, methodology variations may impact swallowability measurements affecting the interpretation of results. Thus, developing robust and valid assessment tools for swallowability is imperative to produce clinically relevant data and inform regulatory decision-making. Collaboration between regulatory agencies and sponsors is warranted to create best practices and ensure high quality swallowability data.

Keywords: Clinical assessment; Regulatory submission; Solid oral dosage form; Swallowability.

Published by Elsevier B.V.