The ability to analyze products directly and non-destructively offers a distinct advantage to biopharmaceutical manufacturers. The presence of subvisible particles poses a safety risk for patients, yet manufacturers have grappled for years with ways to efficiently identify, and then remove, them from cell therapies and other parenteral solutions.
Several possible analytical approaches have been proposed in the past few years, such as backgrounded membrane imaging, which may be effective with working with limited sample material, and imaging flow cytometry, which was suggested as providing supportive data but not for routine use for quality control.
“Analysis systems based on the two leading methods–light obstruction and counting microscopic particles–generally require destruction of the sample material during the measurement process,” Changhuei Yang, PhD, professor of electrical engineering at California Institute of Technology (CalTech), tells GEN.
Yang and colleagues at Amgen and CalTech may have a solution. Writing in the Journal of Pharmaceutical Sciences, they detail their work to develop a direct, non-destructive analyzer that determines whether subvisible particles are present in injectable and ophthalmic solutions. Notably, their approach analyzes subvisible particles in their containers, thereby avoiding the need to remove [and hence destroy] product for testing.
Reducing distortion
Yang and his team developed a custom sample housing for the analyzer that minimizes optical distortions caused by the curvature of the product vials. During the analysis, the equipment used Mie scattering theory and existing refractive indices to model side scattering from any individual particle.
The scientists then estimated the spherical particle size and particle concentration. “These measurements are performed rapidly and simultaneously for all the particles seen through a light-sheep microscope,” Yang says. “As such, the system is also able to generate a size-sorted particle concentration report of the sample.”
To test the accuracy of this approach, Yang and colleagues evaluated polystyrene bead suspensions in ISO 2R and ISO 6R vials. Results showed the analyzer accurately detected subvisible particles in those containers and sorted them “into commonly used size bins–equal to or greater than 2, 5,10 and 25 microns–and quantified particle concentration between 4.6e2 to 5.0e5 particles/mL.”
Consequently, subvisible particles of protein, plastic, glass, metal, dust, protein, surfactant degradation, and silicon oil droplets, for example, can be detected effectively, even among filled product. Additional benefits of non-destructive subvisible particle testing include “improved data quality and reduced resource burden,” the scientists note.
Applications include stress testing and stability monitoring of drug products, particularly once they are in their primary containers.
