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 DID YOU KNOW… The vast majority of inclusions in filled products fall into three categories: Fragments, Flakes and Particles
The prevention of particles in filled pharmaceutical products is a perpetual, costly but absolutely vital activity for all fillers in this industry. These particles are generally referred to as inclusions but may also be identified by several more specific names such as: fragments, particles, flakes, or foreign material.
The difficulty in identifying and eliminating inclusions has increased due to evolving stringency that has changed from restrictions on particles that were readily visible without magnification to the current practice of filtering product and examining any filtrate at magnifications up to 25X. The issue complexity is increased due to the distinctly different types of inclusions that can be introduced into product. They have been shown to have varying compositions, shapes and sources.
Thus, the key to any corrective action is an accurate identification of the specific type of inclusion as this often is a strong indication of the source.
A typical inclusion analysis involves both a detailed microscopic examination of the inclusions in order to document the size, shape and surface features, followed by detailed analysis with a Scanning Electron Microscope (SEM) with Energy Dispersive X-Ray (EDX) capabilities to identify compositional attributes.
AGR routinely works with all types of fillers (Spirits, Beverage and Wine), in addition to pharmaceutical companies to identify the type and possible sources of inclusions identified in their products. While there can be a number of inclusion types, the vast majority can be grouped into three general categories:
The first is glass fragments due to chipping or breakage. These fragments are comparatively large, often ranging between 0.025 to 0.070 inches. Each fragment exhibits fracture surface markings and may have an original molded surface from the container. These fragments often have the same composition as the host vial in which they are found. The identification of chip sites within the finish region of the host vial is a common source of this type of fragment. Less frequently, in the absence of a chipped site of the host vial, smaller glass fragments (<0.015 inches) have been attributed to a previously filled item that was fractured with the fragments carried into the host vial by the filling tube.
A second category is glass flakes with maximum sizes typically less than 0.010 inches. Generally, the flakes are thin, contain an original surface and can be flat or slightly curved. In a few instances, extreme curvature causes the flake to appear rolled like a “scroll.” The source of these flakes is delamination of the inside glass surface. This is a condition in which the flakes originate of the inside surface and peel away due to reaction between the filled product and the glass surface.
A third category is particles that often consist of non-glassy appearing material exhibiting varying shapes. The sources for this category varies and can include small metal particles, portions of the stopper, foreign material in the drug product or possibly drug product that has separated from solution.
If you need expert help identifying your inclusions Contact Us
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