Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients

Abstract

<jats:title>Abstract</jats:title><jats:p>One of the fundamental principles guiding the pharmaceutical quality of parenteral products is to prevent injecting contaminants from microbiological, chemical or physical sources. It is just as difficult to ensure the absence of chemical and particulate contaminants in injectable products as it is to weigh up the microbiological risk. The problem of particulate matter is mainly related to the preparing and administrating of injectable drugs rather than through the contamination of marketed products. Particulate contamination also arises</jats:p>

Analysis of particulate exposure during continuous drug infusion in critically ill adult patients: a preliminary proof-of-concept in vitro study

“…There are different causes of particulate contamination of IV fluids. It can occur during the manufacture or preparation of drug solutions or result from drug incompatibility [ 21 ]. It may be relevant to assess the extent to which particles originate from the reconstitution of injectable drugs.…”

Update on the Use of Filters for Parenteral Nutrition: An ASPEN Position Paper

“…All intravenous fluids contain particulate contamination, defined as mobile undissolved particles, unintentionally present in a parenteral solution 44 . These particles may consist of dust, glass, rubber, plastic, silicone, fibers, metal, and precipitates resulting from drug incompatibility 45–47 . The complex nature of PN admixtures and the need for multiple additives can induce alterations in the pH and concentration of nutrients in the solution that results in drug and mineral precipitation 9,36,48 .…”

“…In recent years, the increasing complexity of intravenous therapy has brought renewed scrutiny to the presence of particulate matter in parenteral fluids. A number of in vitro studies have simulated multidrug protocols for neonatal, pediatric, and adult patients, many involving drug administration in conjunction with PN admixtures 47,48,52,60,67–70 . Variation exists in the lower range of particle sizes evaluated in these studies, which may reduce the ability to accurately determine the total number of particles in a given solution.…”

“…44 These particles may consist of dust, glass, rubber, plastic, silicone, fibers, metal, and precipitates resulting from drug incompatibility. [45][46][47] The complex nature of PN admixtures and the need for multiple additives can induce alterations in the pH and concentration of nutrients in the solution that results in drug and mineral precipitation. 9,36,48 Precipitates containing calcium and phosphate pose a serious risk during PN therapy.…”

Innovation in the Transport of Cytotoxic Drugs by a Pneumatic Transport System

“…This study deals with concentrated solutions in glass vials which is different to our purpose (plastic packaging and diluted solutions). They concluded that, even if the loss of monomeric protein was not large enough to affect potency of the protein, the subvisible particles have the potential to affect immunogenicity, besides the other clinical consequences [8]. So, as recommended, some anticancer drugs are being filtered with a 0.2 µm filter before their administration.…”