Clinical studies in herbal drug formulation and development: challenges and regulatory perspectives

Abstract Herbal medicines have gained considerable global attention due to their therapeutic potential, long history of traditional use, and relatively favorable safety profiles. Despite their widespread acceptance, integrating herbal products into evidence-based modern medicine requires systematic scientific validation to confirm safety, efficacy, and quality. This narrative review presents a critical overview of the major stages involved in the development of herbal drug formulations, focusing on the transition from traditional therapeutic use to clinically validated applications. Key aspects such as phytochemical characterization, quality standardization, preclinical pharmacological evaluation, and phased clinical trials are analyzed. Rather than treating herbal products as conventional single-entity small molecules, this review explores how the complex chemical matrices of botanicals alter conventional development paradigms. The review examines existing regulatory frameworks governing herbal medicines, including guidelines issued by the World Health Organization (WHO), the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and Indian regulatory authorities such as the Ministry of AYUSH and the Central Drugs Standard Control Organization (CDSCO). Several challenges associated with herbal drug development are highlighted, including multi-constituent variability, limited high-quality randomized controlled trials, and inconsistencies in regulatory requirements across global jurisdictions. Strengthening methodological rigor, improving quality control practices, and harmonizing international regulatory standards are essential to establish a robust scientific evidence base and support the safe and effective integration of herbal medicines into global healthcare systems.