The particle puzzle

Dr Ravikiran Allada, CEO, Alcoax outlines a scientific framework using advanced techniques, to systematically identify and control visible particles in injectables

- 

Injectable medications, essential for the treatment of numerous medical conditions, demand the highest standards in formulation, manufacturing, and packaging. Among the various quality concerns, the presence of visible particles has consistently been one of the most critical issues. Historically, visible particles have accounted for more than 20 per cent of injectable product recalls1, highlighting their significant impact on product quality and patient safety.

These particles—whether originating from manufacturing processes, packaging materials, or even the formulation itself—pose a potential hazard to patients, as they can lead to embolism, blockage of blood vessels, or immune system reactions. As a result, regulatory agencies and pharmacopeia such as the United States Pharmacopeia (USP) and the European Pharmacopoeia (EP) have established standards to ensure the absence of visible particles in injectable drug products it requires 100 per cent of the product inspection. The particles are often detected during visual inspection, microscopic examination, or automated detection systems.

Controlling visible particles remains a major challenge in the pharma industry. Firstly, it is practically impossible to guarantee that products are entirely free from visible particles, even with robust product manufacturing control measures in place—hence, visual inspection and manual checks are still necessary. Secondly, there is no clear or quantitative definition of visible particles. For instance, the USP states that products should be "essentially free" from visible particles, while the EP uses the term "practically free" These qualitative definitions are open to subjective interpretation and are not harmonised across pharmacopoeias. In contrast, sub-visible particles (SVPs) are well-defined and standardised, with specific limits on particle size and count, offering a much more consistent regulatory framework [2, 3].