Highlighted Services: Particulate Analysis of Injectable Products

Particulate matter in parenterals or injectable products remains of great concern to both the manufacturer and consumer. Product recalls due to particulate contamination continue to be reported in the news media. The most common foreign particulate matter includes stainless steel, microbial contaminants, synthetic and natural fibers, and glass flakes from vial delamination. Particulate analysis is essential to identifying the composition of the foreign material and determining its source.

Pictures from a particulate analysis course, showing the most common foreign particulate found in injectables.

Diagram of the analytical approach used for particulate analysis.

The first step is examination and documentation. When a sample comes in, it is examined with a stereomicroscope to make sure you can find the particulate or contaminant of interest. Once the particle contaminant is located, a picture is taken for documentation.

Picture from a particulate analysis case study, showing an extraneous fiber in an injectable vial.

After examination and documentation, the next step is to isolate the particulate for analysis. For parenteral products, a filtration apparatus on a Class 100 (ISO 5) clean bench is used. In most cases, particle-free water would be used for the filtration; however, if the sample is not compatible with water, a different solvent would be needed. Filtration lab blanks are prepared to make sure no particles are introduced during the process. After filtration, the filters are examined to ensure the particle of interest was properly isolated.

Class 100 (ISO 5) clean bench with filtration apparatus and stereomicroscope.

Once the particulate matter is isolated, the next step is to figure out which analytical techniques to use. With the stereomicroscope, you can usually tell if something is a polymer, fiber, cellulose, elastomeric or glass. For polymeric materials, the sample would be analyzed by infrared spectroscopy (IR), polarized light microscopy (PLM) and Raman spectroscopy. For glass and/or metallic materials, the sample would be analyzed by polarized light microscopy and scanning electron microscopy (SEM).

With a complementary analytical approach by SEM, IR, Raman and PLM, you can rapidly identify unknown particulate.