Visible Particles from Polysorbate DegradationCases & Perspectives

Particles…

• represent an obligatory cQA for parenteral products

• are often a focus topic in audits and inspections

• are still the major reason for product recalls

• aspiration of zero visible particles is desirable, but unrealistic

Particles & Parenterals – not best friends

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• Standardized procedure: unaided human eye, light box, controlled light intensity (2000 – 3750 lx)

• Analysis upon gentle agitation (e.g. swirling)

• Well trained operators: – Periodic eyesight tests– Initial and continuous training – Performance qualification – Periodic performance control

USP <790> Visible Particulates in Injections – Manual Visual Inspection

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Ph. Eur. 2.9.20. “Particulate Contamination: Visible Particles”

Issue: No clear and harmonized definition of visibility available

Visual Inspection – Process Flow Scheme for Liquid Products

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Case study:Visible Particles in Biopharmaceutical Development Products

Case Study: Visible Particles in Biopharmaceutical Development Products

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Case Study: Particle Forensics – Morphology & Elemental Composition

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Case Study: Particle Forensics – Chemical Composition

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Case Study: Source of Free Fatty Acids – most likely PS20

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Case Study: Root Cause within the Manufacturing Process?

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Case Study: Mechanism of PS20 Degradation

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Case Study: Visible Particles in Biopharmaceutical Development Products

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Ingrid AuernhammerFlorian BaizMartin DassThomas EhrmannBeate EyrichCornelia GappPatrick GaridelJulia Groß-RotherFelix Halbach

Peter HappersbergerSilke HövelWerner KlicheMarius LöfflerTheresa MüllerDagmar RädelKatrin ReinhardtMarkus RieggerThomas Schwab

Maik VeeldersPeter WanjaTill WengerRobert WildJustine Witosch

and many more…

Acknowledgements

CMC Strategy Forum 2020/Washington - Visible Particles from Polysorbate Degradation - Felix Nikels 13Jan 27, 2020

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2019