Exploring the challenges faced by generic version of complex drugs: a scoping review.

Background: Complex generics can be defined by their complex active pharmaceutical ingredients (APIs), formulations, dosage forms, routes of administration, and drug device combinations which significantly pose challenges in scientific advancement and regulatory approvals. The present review aims to investigate, identify, and classify the critical challenges faced by different stakeholders and the strategies adopted to address these challenges across the developmental stage till the post-approval phases of complex generics.

Method: We followed the Preferred Reporting Items for the Scoping Reviews Extension for Systematic Reviews and Meta-Analyses (PRISMA-ScR) guidelines for the systematic search conducted across various databases such as PubMed, EMBASE, Scopus, and Web of Science (January 1, 2014, to August 22, 2024). English language articles that addressed various challenges as well as innovative strategic approaches were included in the study. Two authors independently reviewed the retrieved papers to reduce the possibility of bias. The screening was performed based on predetermined inclusion and exclusion criteria.

Results: A total of 1718 studies were retrieved from the database searches, from which 24 met the eligibility criteria. The selected articles were from the USA, the European Union, India, Russia, Taiwan, China, and Malaysia. The formulation challenges (17 articles), analytical challenges (19 articles), clinical challenges (18 articles), critical process parameter-related challenges (17 articles), critical quality attribute-related challenges (19 articles), and regulatory challenges (21 articles) were the major challenges of complex generics. The use of advanced sophisticated analytical equipment as well as orthogonal bioanalytical testing, the implementation of a dynamic regulatory cross-checking system, the development and use of machine learning and artificial intelligence tools, and the development of quality-by-design approaches and models have been recognized as the best methods for addressing these challenges.

Conclusion: This review addresses critical gap by providing a systematic summary of stakeholder-reported barriers and novel mitigation approaches in the complex generics domain. It highlights the urgent need for harmonized global regulatory guidelines, advance analytical tools, and strategic stakeholder collaboration to hasten the development and availability of high-quality complex generics.

Scoping review registration: The review was not registered.