Conducting Clinical Risk Assessments for Visible Particulate Matter in Parenteral Preparations

Abstract

Visible particulate matter in injectables presents one important question for consideration: “What are the potential implications to the patient?” The risks of visible particulate matter to patient safety have been comprehensively reviewed elsewhere. However, the methods used to assess and characterize the risks have been explained with various degrees of specificity and supporting rationale. To date, the assessment process lacks the necessary consensus to permit a more standardized and consistent approach to evaluate the potential patient risks.

The purpose of this commentary is to provide one model that might be used to evaluate the three most relevant factors impacting the risk of injections containing particulate matter: the source of the particle, particle-specific attributes, and characteristics of the intended patient population. Each of these factors is considered with a focus on the more important aspects that might be relevant to imposing untoward risk. The discussion also includes the importance of differentiating the concepts of risk assessment from risk acceptance when establishing criticality levels for product attributes.

LAY ABSTRACT: Pharmaceutical products intended for injection or infusion may contain particles that can emanate from different sources. Some particles, such as suspensions, are intended. Others are not, and those particles are the subject of rigorous manufacturing process controls to limit their presence and reject units that might contain visible defects. However, no technology exists that can prevent or eliminate all particles from these products. As a result, comprehensive risk assessments must be conducted to identify the capability of manufacturing systems to limit particles and detect and reject atypical units. An essential component of this strategy includes understanding the potential impact that injected or infused particles might have to a patient receiving these medications. The purpose of this paper is to provide one approach that clinicians might use to conduct that risk assessment by discussing the important aspects of the source of the particle, its characteristics (such as size or composition), and the relevant patient factors such as the illness being treated or other medical conditions that might impact the risk to these patients if particles are injected or infused.