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

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Complex generics present significant scientific and regulatory hurdles due to intricate active pharmaceutical ingredients (APIs), formulations, dosage forms, administration routes, and drug-device combinations.
• These challenges impact various stakeholders throughout the development and post-approval lifecycle of complex generic drugs.

Purpose of the Study:

• To systematically investigate, identify, and classify the critical challenges encountered in complex generics development.
• To analyze the strategies employed by stakeholders to overcome these challenges from development to post-approval phases.

Main Methods:

• A systematic scoping review was conducted following PRISMA-ScR guidelines, searching databases like PubMed, EMBASE, Scopus, and Web of Science (Jan 2014 - Aug 2024).
• English language articles addressing challenges and strategic approaches in complex generics were included after independent review by two authors based on predefined criteria.

Main Results:

• Out of 1718 retrieved studies, 24 met the eligibility criteria, with publications from the USA, EU, India, Russia, Taiwan, China, and Malaysia.
• Major challenges identified include formulation (17 articles), analytical (19), clinical (18), critical process parameters (17), critical quality attributes (19), and regulatory aspects (21).
• Effective strategies involve advanced analytical equipment, orthogonal bioanalytical testing, dynamic regulatory systems, machine learning/AI tools, and quality-by-design (QbD) approaches.

Conclusions:

• This review systematically summarizes barriers and mitigation strategies for complex generics, addressing a critical knowledge gap.
• There is an urgent need for harmonized global regulatory guidelines, advanced analytical tools, and enhanced stakeholder collaboration to accelerate the development and availability of high-quality complex generics.