USFDA Warning Letters: An Analysis of Compliance in Over-the-Counter Drug Products (2020–2024)

Abstract

Over-the-counter (OTC) drug products are a critical component of the U.S. healthcare system, requiring stringent regulatory oversight to ensure their safety, quality, and efficacy. Despite the U.S. Food and Drug Administration’s (USFDA) continuous surveillance, persistent non-compliance issues necessitate enforcement actions such as Warning Letters (WLs). This study aims to identify recurring compliance challenges and regulatory trends affecting OTC products by analyzing WLs issued by the Center for Drug Evaluation and Research (CDER) between January 2020 and September 2024. A total of 3041 WLs were reviewed, of which 573 were issued by CDER for drug products, and 202 specifically targeted OTC manufacturers. These WLs were categorized based on the nature of violations to detect enforcement patterns. Labeling deficiencies emerged as the most frequent violation, followed by cGMP non-compliance and product adulteration. Furthermore, there were notable concerns regarding the adulterated products and compliance with cGMP standards, pointing to gaps in manufacturing processes and oversight. The annual WL count for OTC products ranged from 36 to 48 in the mentioned time period, indicating ongoing systemic concerns rather than isolated incidents. This study also emphasises the major violation case studies highlighting post-WL corrective and preventive actions (CAPA), providing valuable industry insights into regulatory expectations and remediation pathways. In summary, the study demonstrates regulatory challenges within the OTC industry, including inadequacies in Labeling, adulteration, and cGMP non-compliance. These challenges emphasize the necessity of enforcement, transparent compliance mechanisms, and uniform standards to ensure the integrity of OTC products in an evolving market.