Chemical and biological differences between original and mimetic pentosan polysulfates

Area of Science:

• Pharmaceutical Sciences
• Biochemistry
• Drug Characterization

Background:

• Pentosan polysulfate sodium (PPS) is a semi-synthetic heparin-like polysaccharide with approved therapeutic uses in humans and animals.
• Its complex structure, derived from beech wood, consists of sulfated glucuronoxylans, making full physicochemical characterization challenging.
• The potential for generic drug applications raises questions about the identity of follow-on PPS products compared to the original.

Purpose of the Study:

• To investigate physicochemical differences between commercially available PPS products and the original formulation.
• To assess functional biological variations among different PPS preparations.
• To determine if follow-on PPS products can be considered identical to the original PPS for regulatory purposes.

Main Methods:

• Analysis of ten PPS preparations from various manufacturers using orthogonal techniques.
• Employing size exclusion chromatography with triple detection, nuclear magnetic resonance (NMR) spectroscopy, and mid-infrared (MIR) spectroscopy.
• Functional assays included measurement of plasma kallikrein generation and FXII activation in human plasma.

Main Results:

• Significant structural variations were identified between PPS products from different sources.
• Distinct differences in biological effects, including plasma kallikrein generation and FXII activation, were observed.
• The study found that follow-on PPS products are not identical to the original, but may be considered similar.

Conclusions:

• Commercially available Pentosan polysulfate sodium (PPS) products exhibit notable structural and biological heterogeneity.
• Follow-on PPS products cannot be deemed identical to the original; they are at best similar.
• Comprehensive studies are necessary to establish the comparable efficacy and safety of these similar PPS products.