Leveraging Formulation Development Experience for Effective Particle Identification

Accelerating Particle Identification: A Critical Need

The primary objective of formulation development is to create a stable, safe, and efficacious product. Drug products must be thermally and photostable, while ensuring that the active pharmaceutical ingredient (API) is compatible with excipients, primary packaging, and container closure systems. Any issue with these components can lead to degradation or aggregation — particularly with biologics — causing the formation of (sub)visible particles. Moreover, avoiding environmental contaminants is essential to maintain product integrity.

The presence of particles is often the first sign of instability. When particles are detected during visual inspection of a drug product batch, the entire batch may be withheld from release, creating intense pressure on the drug developer to quickly identify the particles and determine their origin. Are the particles a result of product aggregation during production, or have they been introduced as contaminants due to inadequate environmental controls?

A service provider with deep expertise in both formulation development and particle analysis can provide comprehensive support across the entire clinical development process and into the commercial stage after the drug is launched in global markets. Partnering with such an organization from the outset ensures the creation of a robust formulation and, critically, enables rapid analysis when unexpected particles are identified during drug product manufacturing. By leveraging their advanced analytical tools and extensive experience in formulation challenges, these partners can quickly pinpoint the cause of the issue, preventing costly delays.

Expertise-Driven Partnerships for Comprehensive Particle Analysis

Recognizing the critical role of particles in product development, Coriolis Pharma has integrated particle characterization and identification services into its formulation development offerings for several years. The process is highly streamlined to ensure rapid turnaround times, with redundant analytical instrumentation and a team of highly trained scientists working in parallel to maintain high throughput. This efficient system allows Coriolis to handle urgent requests without compromising quality. Furthermore, a well-established, multi-step approach guarantees a thorough evaluation of particle composition, size, and other key characteristics based on the client’s specific needs.

Clear, Multi-step Particle Analysis Process

Clients provide particles either as isolated samples or within liquid product samples. In the case of liquid samples, Coriolis Pharma’s particle identification process begins with a visual inspection to confirm the client’s findings. High-resolution brightfield images of the product are taken to document any visible particles. The particles are then isolated using a filtration step, where the filter traps particles larger than 2 µm in diameter. From the collected sample, typically 5–10 particles with varying characteristics are selected for analysis.

A range of advanced techniques is employed to identify and characterize particles down to a size of 10 µm. These include light microscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), and, optionally, liquid chromatography-mass spectrometry (LC-MS).

Light microscopy provides information on particle size and morphology, while FTIR helps determine chemical composition, identifying substances such as cellulose fibers, plastics, or proteins. SEM-EDX provides high-resolution imaging of particle morphologies and further chemical characterization through elemental analysis. The combination of FTIR-ATR and SEM-EDX is typically used to achieve a high level of confidence in identifying unknown particles. LC-MS is particularly useful for identifying protein particles within biologic products, providing detailed information through intact mass determination or peptide mapping. Additional methods like Raman spectroscopy, microflow imaging, and light obscuration are available upon request to further define the number and size distribution of particles.

For liquid samples, only a small volume of sample containing the particle of interest is required for filtration. If Coriolis identifies numerous particles that the client had not previously detected, further analysis may be conducted. For instance, extrinsic contaminants like cellulose particles are unlikely to grow over time, whereas intrinsic contaminants, such as protein aggregates, could increase in size. This distinction is crucial for clients, aiding them in optimizing their processes and preventing future product issues.

Fast-Track Particle Characterization and Identification

If observation of particulate impurities leads to an out-of-specification (OOS) result during product manufacturing, the drug developer must take immediate action. Samples of concern must be analyzed as quickly as possible to identify the particle source and decide on the next steps. Coriolis offers a fast-track service for this. Within three days, the results of the particle analysis are reported to the client so appropriate measures can be taken by the client without further delay.

In addition to particle identification as a standalone service, clients may require a more in-depth analysis to determine the origin of the particles and the conditions leading to their formation. In such cases, Coriolis provides more comprehensive identification services, helping clients understand the root cause of particulate contamination. This can often evolve into a full formulation development project, including in-use stability studies, where Coriolis designs a robust formulation to address the identified issues.

Leveraging Formulation Expertise for Superior Particle Analysis

Unlike many providers of particle identification services, Coriolis Pharma stands out as a formulation development company with deep expertise in creating robust drug formulations for biologics and cell and gene therapies. The focus on biopharmaceuticals, combined with extensive experience addressing general stability issues, potential negative interactions between excipients and drug substances, and degradation or aggregation mechanisms, is a key advantage. This expertise allows Coriolis to place particle identification results within the broader context of product formulation challenges, providing clients with actionable insights beyond simple analytical results.

For clients in the field of cell and gene therapies, Coriolis’ capabilities also extend to the analysis of viral vectors and other specialized samples requiring containment up to Biosafety Level 2. Coriolis Pharma works as an extension of its clients, collaborating closely with their subject matter experts to ensure a streamlined and integrated approach to particle identification, offering a higher level of partnership and problem-solving.