From Palm Refinery Residues to Vaccine Adjuvants: Qualifying PFAD Derived Squalene Through Quality-by-Design and Immunological Comparability

Abstract

Squalene-based oil-in-water emulsions underpin established vaccine-adjuvant platforms, while palm fatty acid distillate (PFAD) provides a potentially recoverable non-animal source of squalene. This qualitative literature review critically integrates research on PFAD separation, pharmaceutical impurities, squalene-emulsion mechanisms, formulation stability, clinical vaccine evidence, and sustainable manufacturing. A 2025 pilot-scale PFAD-related separation study demonstrates substantial squalene enrichment, but reported chemical purity and recovery do not establish suitability for injectable use. Research on MF59, AS03, and experimental emulsions demonstrates formulation-specific immune effects and clinical utility; none directly validates PFAD-derived squalene as an interchangeable input. The synthesis identifies six connected gaps: feedstock representativeness, impurity-specific qualification, oxidative
stability, scaled manufacturing reproducibility, formulation-matched biological comparability, and supply-chain lifecycle performance. We propose a five-gate translational pathway from feedstock characterization to material qualification, emulsion control, nonclinical testing, and context-specific regulatory and clinical evaluation. Alternative microbial and semisynthetic sourcing routes provide critical benchmarks. The review concludes that PFAD derived squalene is a credible research candidate for diversifying vaccine-manufacturing inputs, but claims of pharmaceutical equivalence, superior immunogenicity, or sustainability must remain conditional on direct comparative evidence. The resulting source-to-vaccine framework establishes testable priorities for multidisciplinary research and risk-based industrial development.