Beyond bioequivalence: a critical overview of the innovator AmBisome as the reference standard for liposomal amphotericin B generics

INTRODUCTION: The advent of liposomal amphotericin B (L-AmB, commercialized as AmBisome) technology represented a paradigm shift in antifungal drug delivery, substantially reducing the severe, well-known nephrotoxicity historically associated with the conventional deoxycholate formulation (D-AmB). Despite this advance, the expiration of the innovator's patent has spurred the global development of generic liposomal preparations, raising critical biopharmaceutical and clinical safety concerns. AREAS COVERED: This article reviews the literature and regulatory landscape of L-AmB and its nanosimilars. A comprehensive search was performed using PubMed, Embase, and Web of Science (1990-2026), focusing on NBCDs, bioequivalence, and clinical safety. The scope includes an evaluation of marketed generic formulations, their regulatory registrations, and published comparative studies. We also discuss the clinical consequences of administering unstable generics during high-dose protocols. EXPERT OPINION: While recognizing the urgent need for affordable generic alternatives to democratize access in low- and middle-income countries (LMICs), we emphasize the necessity for stringent, internationally harmonized regulatory standards beyond conventional bioequivalence. Safeguarding biopharmaceutical fidelity is an indispensable clinical imperative to protect vulnerable patients from the severe hidden costs of therapeutic failure and drug-induced toxicity.