Industry Perspective on the Medical Risk of Visible Particles in Injectable Drug Products

Particulate Generation Mechanisms during Bulk Filling and Mitigation via New Glass Vial

“…The presence of foreign particulate matter contamination in parenteral drugs poses risks to patients and continues to be a leading cause of drug recalls (1)(2)(3)(4). Recent medical risk-based approaches for assessing the presence of a low quantity of particles in the drug product conclude that the overall risk can vary considerably based on factors such as patient health, nature of the particle, and route of administration (3,4). For low-risk routes of administration (subcutaneous and intramuscular) of a drug into a healthy patient, clinically meaningful harm due to a few visible, sterile particles is considered to be unlikely (4).…”

“…Recent medical risk-based approaches for assessing the presence of a low quantity of particles in the drug product conclude that the overall risk can vary considerably based on factors such as patient health, nature of the particle, and route of administration (3,4). For low-risk routes of administration (subcutaneous and intramuscular) of a drug into a healthy patient, clinically meaningful harm due to a few visible, sterile particles is considered to be unlikely (4). In contrast, neonates, infants, elderly, chronically sick, and immune-compromised patients injected intravenously are more vulnerable to the medical effects of such particulate contamination (3,4).…”

“…For low-risk routes of administration (subcutaneous and intramuscular) of a drug into a healthy patient, clinically meaningful harm due to a few visible, sterile particles is considered to be unlikely (4). In contrast, neonates, infants, elderly, chronically sick, and immune-compromised patients injected intravenously are more vulnerable to the medical effects of such particulate contamination (3,4). Documented clinical adverse effects in patients who have received injections containing foreign particulate matter contamination include phlebitis, pulmonary emboli, pulmonary granulomas, immune system dysfunction, pulmonary dysfunction, infection, and death (1,(3)(4)(5)(6)(7)(8)(9)(10).…”

Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients

“…There are two types of injectable drug particulate matter according to its source [11]: 1) intrinsic particles, defined as those initially associated with the solution which have not been eliminated either by filtration or by precipitation from the solution, and 2) extrinsic particles, defined as those that contaminate the container or solution during manufacture or preparation of drug solutions. Some of these have been described [12], including, for example, fibres, dust, rubber or silicone and have been known for some years, which explains the limited use of glass ampoules today in favour of plastic bottles or pods to ensure patient safety [10].…”

“…It is just as difficult to assess the risk of microbiological contamination in injectable products as it is to ensure the absence of particulate contamination in these same products [10]. Contamination of fluids with bacteria, endotoxins and/or particles has been observed with intravenous (IV) infusion therapy.…”