A Pharmacy bulk package is a container of a sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture program and are restricted to the preparation of admixtures for infusion or, through a sterile transfer device, for the filling of empty sterile syringes.

The closure shall be penetrated only one time after constitution with a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. The Pharmacy bulk package is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area).

Designation as a Pharmacy bulk package is limited to preparations from Nomenclature categories 1, 2, or 3 as defined above. Pharmacy bulk packages, although containing more than one single dose, are exempt from the multiple-dose container volume limit of 30 mL and the requirement that they contain a substance or suitable mixture of substances to prevent the growth of microorganisms.

Where a container is offered as a Pharmacy bulk package, the label shall (a) state prominently “Pharmacy Bulk Package—Not for direct infusion,” (b) contain or refer to information on proper techniques to help assure safe use of the product, and (c) bear a statement limiting the time frame in which the container may be used once it has been entered, provided it is held under the labeled storage conditions.

Where used in this Pharmacopeia, the designation Large-volume intravenous solution applies to a single-dose injection that is intended for intravenous use and is packaged in containers labeled as containing more than 100 mL. The designation Small-volume Injection applies to an Injection that is packaged in containers labeled as containing 100 mL or less.

The Pharmacopeial definitions for sterile preparations for parenteral use generally do not apply in the case of the biologics because of their special nature and licensing requirements (see Biologics 1041).

Observe special care in the choice and use of added substances in preparations for injection that are administered in a volume exceeding 5 mL. The following maximum limits prevail unless otherwise directed: for agents containing mercury and the cationic, surface-active compounds, 0.01%; for chlorobutanol, cresol, phenol, and similar types of substances, 0.5%; and for sulfur dioxide, or an equivalent amount of the sulfite, bisulfite, or metabisulfite of potassium or sodium, 0.2%.

A suitable substance or mixture of substances to prevent the growth of microorganisms must be added to preparations intended for injection that are packaged in multiple-dose containers, regardless of the method of sterilization employed, unless one of the following conditions prevails: (1) there are different directions in the individual monograph; (2) the substance contains a radionuclide with a physical half-life of less than 24 hours; and (3) the active ingredients are themselves antimicrobial. Such substances are used in concentrations that will prevent the growth of or kill microorganisms in the preparations for injection. Such substances also meet the requirements of Antimicrobial Effectiveness Testing 51 and Antimicrobial Agents—Content 341. Sterilization processes are employed even though such substances are used (see also Sterilization and Sterility Assurance of Compendial Articles 1211). The air in the container may be evacuated or be displaced by a chemically inert gas. Where specified in a monograph, information regarding sensitivity of the article to oxygen is to be provided in the labeling.

Select one or more containers if the volume of the container is 10 mL or more, three or more if the volume is more than 3 mL and less than 10 mL, or five or more if the volume is 3 mL or less. Individually take up the contents of each container selected into a dry hypodermic syringe of a rated capacity not exceeding three times the volume to be measured and fitted with a 21-gauge needle not less than 2.5 cm (1 inch) in length. Expel any air bubbles from the syringe and needle, and then discharge the contents of the syringe, without emptying the needle, into a standardized, dry cylinder (graduated to contain rather than to deliver the designated volumes) of such size that the volume to be measured occupies at least 40% of the cylinder's rated volume. Alternatively, the contents of the syringe may be discharged into a dry, tared beaker, the volume, in mL, being calculated as the weight, in g, of Injection taken divided by its density. The contents of up to five 1- or 2-mL containers may be pooled for the measurement, provided that a separate dry syringe assembly is used for each container. The content of containers holding 10 mL or more may be determined by means of opening them and emptying the contents directly into the graduated cylinder or tared beaker.

The volume is not less than the labeled volume in the case of containers examined individually or, in the case of 1- and 2-mL containers, is not less than the sum of the labeled volumes of the containers taken collectively.

For Injections in multiple-dose containers labeled to yield a specific number of doses of a stated volume, proceed as directed in the foregoing, using the same number of separate syringes as the number of doses specified. The volume is such that each syringe delivers not less than the stated dose.

For Injections containing oil, warm the containers, if necessary, and thoroughly shake them immediately before removing the contents. Cool to 25 before measuring the volume.

For Injections in cartridges or prefilled syringes, assemble the container with any required accessories such as a needle or plunger. Following the same procedure as above, and without emptying the needle, transfer the entire contents of each container to a dry, tared beaker by slowly and constantly depressing the plunger. Weigh, and calculate the volume as described above. The volume of each container is not less than the labeled volume.

For large-volume intravenous solutions, select 1 container, and transfer the contents into a dry measuring cylinder of such size that the volume to be measured occupies at least 40% of its rated volume. The volume is not less than the labeled volume.