Generally, no. Unless the multiple-dose container is labeled to yield a specific number of doses of a stated volume, there is no limit to the number of withdrawals that may be made a multiple-dose container before the drug is depleted or reaches its expiration date. The primary concern with multiple-dose containers is the potential for contaminating the product during multiple penetrations through the container stopper. Although the expiration date assigned to such products would be based on the stability of the drug product, stability protocols should include requirements for testing and evaluating container-closure integrity. Container-closure integrity testing may include physically testing the closure seal by using a leak test and monitoring the system’s ability to prevent microbial contamination. For multiple-dose injection product containers, functionality testing can include a self-sealing capacity test involving multiple penetrations of a hypodermic needle through the container stopper (see USP references below). Furthermore, injectable drug products in multiple-dose containers are generally formulated with an antimicrobial agent or preservative—or they contain inherently antimicrobial ingredients—and must meet requirements in accordance with the approved application (new drug application/abbreviated new drug application, biologics license application) and/or USP requirements.
