Analysis of subvisible particles and aggregates in GMP compliance

Coriolis is cGMP accredited by local regulatory authority and  have been re-inspected successfully by the authority and audited by several clients. With a strong focus on analysis of subvisible particles (SVP), we feature the following methods in full GMP compliance:

Light obscuration (LO) (USP <787>, USP <788>, USP <789>, Ph.Eur. 2.9.19.)

• Quantification of particles ≥ 1 μm
• Pharmacopoeia method for the determination of subvisible particles ≥ 10 μm and ≥ 25 μm (USP, Ph. Eur.)
• Development for Low volume method in accordance with USP <787>
• Vast experience with high-concentration / high-viscosity formulations
• Vast experience with ophthalmology products

Micro-Flow Imaging (MFI)

• Quantification, characterization and visualization of particles ≥ 1 μm
• Particle images and shape analysis
• Customized filter development for differentiation between particles of different origin (protein, silicone oil droplets, filter shedding, etc.)
• High sensitivity for translucent (protein) particles
• Referred to by regulatory authorities as orthogonal method to light obscuration
• Product-specific validation of MFI methods

Turbidity / Nephelometry

• Quantification of turbidity according to Ph.Eur.
• Suitable for stability studies

Typical projects involve product-specific method development and subsequent compendial method verification or method validation. Release testing or routine analysis (supporting in-use or stability studies) is performed based on established Testing Procedures. At Coriolis we have a lot of experience in establishing the best subvisible particle (SVP) analytics for the following areas:

• SVP for high-concentration formulations
• SVP for (standard) formulations
• SVP for Ophthalmology products
• SVP for in-use stability
• SVP for gene therapy products and virus formulations (up to biosafety level 2)

Relevant Coriolis publications

Gühlke M. et al., Taking subvisible particle quantitation to the limit: Uncertainties and statistical challenges with ophthalmic products for intravitreal injection. J Pharm Sci. 2019 Nov

Weinbuch D. et al., Light obscuration measurements of highly viscous solutions: sample pressurization overcomes underestimation of subvisible particle counts. AAPS J. 2014 Sep

Weinbuch D. et al., Micro-flow imaging and resonant mass measurement (Archimedes)—complementary methods to quantitatively differentiate protein particles and silicone oil droplets. J Pharm Sci. 2013 Jul

Hawe A. et al., Pharmaceutical feasibility of sub-visible particle analysis in parenterals with reduced volume light obscuration methods. Eur J Pharm Biopharm. 2013 Nov

View more Coriolis publications