Particle Identification for Troubleshooting Drug Development

Different methods to identify particles for your product lifecycle management

Particle identification is an essential aspect of drug development and formulation, as visible and subvisible particles can arise at any stage of the development process, from preclinical to commercial. Particles can significantly impact the safety, efficacy, and stability of pharmaceutical products. During the lifecycle of the product, they may arise from various sources such as raw materials, packaging, environmental contaminants, or the degradation of the drug substance or excipients in the formulation itself. Identifying and characterizing these particles is essential for root cause analysis and to ensure product quality, regulatory compliance, patient safety and support optimizing the manufacturing process.

Particles in pharmaceutical formulations can appear in a wide range of sizes, influenced by their origin. Extrinsic contamination may result in a single, very large particle, whereas intrinsic particles—stemming from the active pharmaceutical ingredient (API)—can vary in size, with sub-visible particles (SVP) to visible particles (VP) potentially forming as the API undergoes aggregation.

• Visible particles, typically larger than 100 micrometers, could be seen with the naked eye. Common techniques for visible particle detection include visual inspection under controlled lighting conditions and light microscopy. These methods help distinguish between intrinsic ( originating from the product itself) and extrinsic particles (originating from packaging or environmental contamination).
• Subvisible particles, ranging from 1 to 100 micrometers, are particularly concerning in biopharmaceuticals because they can affect the product’s stability and potency. Identifying these particles requires more sophisticated techniques due to their small size and potential to form larger aggregates. For subvisible particle identification, spectroscopic techniques such as Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy and Scanning Electron Microscopy with Energy-Dispersive X-Ray Spectroscopy (SEM-EDX) are utilized for chemical identification of particles, ensuring accurate determination of their composition.

Understanding the root cause of particle formation is critical to maintaining product quality and safety. To achieve this, it is essential to characterize and identify all size classes of particles present using advanced techniques. By leveraging these methods, we can accurately determine the size distribution, identity and morphology of the particles, enabling a thorough investigation into their origin and ensuring effective solutions to mitigate potential risks.

Coriolis Pharma has worked with more than 930 compounds such as nucleic acids, peptides, therapeutic proteins and more. If you would like to get more information about particle identification in biopharmaceuticals, access the Coriolis publication here for more details. 

Valuable insights for your drug development journey

As regulatory scrutiny continues to rise, robust particle identification and characterization methods remain indispensable in drug development and formulation, guaranteeing high-quality pharmaceutical products that are safe and effective for patient use. Read more on how Coriolis Pharma’s fast track analytics expertise in the industry help you with your drug development.

• Troubleshooting : Effective particle identification enhances the understanding of particle sources, guiding team of experts in selecting appropriate excipients and manufacturing processes to minimize particle formation.
• Quality control and risk minimization: Particle Identification aids in risk assessment and mitigation strategies, ensuring product stability and safety throughout its shelf life.
• Cost and time efficiency : Proactive particle control along the drug development process minimizes manufacturing losses and maximizes profitability. Coriolis Pharma’s fast track particle analytic services help you to save time during your late phase. Meet with Coriolis team of experts, who can analyze your samples with minimal lead time and deliver results directly from the lab bench so you can resolve the underlying cause of particle formation and secure your development success.

From Visual Inspection to Identification

At Coriolis Pharma, a broad range of samples can be analyzed such as solid (lyophilized, powder etc.) and liquid samples, while particles starting at 10 micrometers to several centimeter can be analyzed. The sampling volume and amount requirements is flexible, and the complete workflow is supported up to Biosafety Level 2 (BSL-2) to also offer this service to cell and gene therapy products. Particle Identification might act as entry point for further investigations in your drug development journey and Coriolis team of experts are ready to provide standardized or customized services depending on your needs.

Drug product development: Importance of in-use stability

In-use stability studies evaluate factors such as dilution effects, storage and handling conditions, surface adsorption, shear forces, extractable volume variations, reconstitution, and aggregate or (sub)visible particle formation. Explore Coriolis Pharma’s in-use stability offerings combined with particle identification services for your next project.