Multi-dose vial (revision 11)

A multi-dose vial, termed a multiple-dose container in compendial language, is a container of an injectable preparation intended to permit withdrawal of successive portions of its contents without change in the strength, quality or purity of the remainder. The definition is functional: it describes an intention and the conditions that make the intention safe, not a size or a shape. A 10 mL vial may be a single-dose or a multiple-dose container depending on its formulation and its labelling.^[1]

Two requirements follow from repeated entry. Because each penetration of the closure is an opportunity for microbial ingress, and because the contents are held at or near room temperature for a period afterwards, a multiple-dose preparation must contain an antimicrobial preservative whose effectiveness has been demonstrated by the challenge testing described in USP <51>. And because the preservative controls but does not eliminate risk, the period during which the container may be used after its first puncture is limited, conventionally to 28 days unless the manufacturer specifies otherwise.^[2][3]

The 28-day convention is frequently misread as a statement about chemical stability. It is not: it derives from the antimicrobial effectiveness of preserved formulations and from infection-control practice, and it is independent of whether the active substance remains within specification. A preparation may be chemically stable for a year and still be discarded at 28 days, and a preparation may lose potency well before 28 days despite its preservative performing perfectly.^[3][4]

USP <659> distinguishes several container categories, and the distinctions govern labelling and use.

Single-dose container

A single-unit container for an article intended for parenteral administration only, used once and discarded. Ampoules and prefilled syringes are inherently single-dose; a vial is single-dose if so labelled.

Multiple-dose container

A multiple-unit container for an article intended for parenteral administration only, permitting withdrawal of successive portions without altering the remainder.

Pharmacy bulk package

A container of a sterile preparation for parenteral use containing many single doses, intended for further dilution or dispensing in a suitable environment, and not for direct administration. Its permitted period after entry is short — commonly stated on the label and typically measured in hours.^[1]

The requirement for a preservative in a multiple-dose container appears in the general requirements for injections, and the demonstration of effectiveness is by the antimicrobial effectiveness test in USP <51>. That test challenges the formulation with specified organisms — Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus brasiliensis — and requires defined log reductions at defined intervals over 28 days. For injectable products the criteria are the most demanding of the product categories the chapter defines.^[2]