Par Pharmaceutical Recalls Treprostinil Injection 20 mg/20 mL (1 mg/mL)

Endo International announced on March 12, 2024 that one of its operating companies, Par Pharmaceutical, is voluntarily recalling one lot of Treprostinil Injection 20 mg/20 mL (1 mg/mL) because of the potential presence of silicone particulates in the particle solution (1).

Treprostinil Injection is a prostacyclin vasodilator used to treatpulmonary arterial hypertension. It is formulated for subcutaneous or intravenous infusion. According to the company, administration of an injectable product containing particulate matter may cause irritation or swelling. More seriously, if the particulates reach the blood vessels, they can travel to organs and block blood vessels, which can cause a stroke or death.

The recalled product was distributed in 20-mL multidose vials as sterile solutions in water for injection. Vials are individually packaged in cartons under NDC #42023-206-01. The impacted lot, 57014, was distributed nationwide to wholesalers and hospitals from June 16, 2022 through Oct. 17, 2022 and has an expiration date of 04/2024.

Written notification about the recall has been sent to wholesale accounts and hospitals that received the affected lot. The company stated in a press release that, “Wholesale distributors and hospital pharmacies that have the product being recalled should immediately discontinue use and stop distribution immediately. If you have further distributed the recalled product, please notify your accounts or any additional locations which may have received the recalled product.”

The company states that it has not received any reports of adverse events related to the recall as of the date of the press release. Adverse reactions may be reported to FDA via it’s MedWatch Adverse Event Reporting program.

There are regulatory guidelines in place to mitigate the problem of particulates. According to the FDA guidance document, Inspection of Injectable Products for Visible Particulates, patient safety can be impacted by visible particles in injectable products (2). The guidance states that companies should develop and implement a “holistic, risk-based approach” to controlling these particulates and preventing contamination. The guidance document states, “The clinical manifestations of adverse events caused by particulate contamination vary and may depend on the route of administration (e.g., intravascular, intravisceral, intramuscular), patient population, and nature or class of the particulates themselves (e.g., physical size or shape, quantity, chemical reactivity to certain cells or tissues, immunogenicity, infectivity, carcinogenicity). Particulates in intravascular or intravisceral injections generally can cause more adverse events than those in subcutaneous or intramuscular injections.”

Risk assessments should be conducted during product development, according to the FDA guidance document, and any visible particulates that may pose a risk should be identified. “Manufacturers should also consider the potential sources of particulates, appropriate analytical methods to monitor them, and mitigation strategies to prevent their presence in the final product,” the guidance document states.

Visual inspection of the product should be part of a program to ensure products are free of contaminates, according to the agency. “During injectable product development, manufacturers should establish procedures for inspecting the product, statistical sampling plan(s), acceptance/rejection criteria, and procedures for evaluating inspection results. Inspection procedures carried over from another site or another product may not always be suitable for a new product,” the agency states in the guidance document.

References

1. FDA. Par Pharmaceutical Issues Voluntary Nationwide Recall of One Lot of Treprostinil Injection Due to Potential for Silicone Particulates in the Product Solution. Press Release. March 12, 2024.
2. FDA. Draft Guidance for Industry,Inspection of Injectable Products for Visible Particulates. (CDER, CBER, CVM, December 2021.