Rational formulation and industrial manufacturing of lipid-based complex injectables: Landmarks and trends

Area of Science:

• Pharmaceutical Sciences
• Biotechnology
• Nanotechnology

Background:

• Lipid-based systems are established drug delivery vehicles.
• Lipid nanoparticles (LNPs) show significant promise for nucleic acid delivery, including mRNA.
• Gene therapy faces challenges in drug delivery and molecular stability.

Purpose of the Study:

• To explore key milestones in approved lipid nanosystem development.
• To provide an overview of technologies and regulations for manufacturing complex lipid nanoformulations.
• To address challenges in scalability, stability, sterility, and regulatory compliance for LNP manufacturing.

Main Methods:

• Review of currently approved lipid nanosystems.
• Analysis of quality-by-design (QbD) principles.
• Exploration of process analytical technology (PAT) for continuous manufacturing.

Main Results:

• LNPs are a breakthrough platform for nucleic acid delivery, addressing gene therapy hurdles.
• Complex multi-batch processes hinder industrial manufacturing of lipid-based delivery systems.
• QbD and PAT are essential for overcoming manufacturing challenges.

Conclusions:

• Transitioning from batch to continuous manufacturing is vital for efficient LNP production.
• Adoption of QbD and PAT principles will enable scalable, flexible, and compliant manufacturing.
• Further development of advanced manufacturing technologies is needed for complex lipid nanoformulations.