The following nomenclature pertains to five general types of preparations, all of which are suitable for, and intended for, parenteral administration. They may contain buffers, preservatives, or other added substances.

pharmacy bulk package

large- and small-volume injections

biologics

Unsaponifiable Matter— Reflux on a steam bath 10 mL of the oil with 15 mL of sodium hydroxide solution (1 in 6) and 30 mL of alcohol, with occasional shaking until the mixture becomes clear. Transfer the solution to a shallow dish, evaporate the alcohol on a steam bath, and mix the residue with 100 mL of water: a clear solution results.

Free Fatty Acids— The free fatty acids in 10 g of oil require for neutralization not more than 2.0 mL of 0.020 N sodium hydroxide (see Fats and Fixed Oils 401).

The label states the name of the preparation; in the case of a liquid preparation, the percentage content of drug or amount of drug in a specified volume; in the case of a dry preparation, the amount of active ingredient; the route of administration; a statement of storage conditions and an expiration date; the name and place of business of the manufacturer, packer, or distributor; and an identifying lot number. The lot number is capable of yielding the complete manufacturing history of the specific package, including all manufacturing, filling, sterilizing, and labeling operations.

Where the individual monograph permits varying concentrations of active ingredients in the large-volume parenteral, the concentration of each ingredient named in the official title is stated as if part of the official title, e.g., Dextrose Injection 5%, or Dextrose (5%) and Sodium Chloride (0.2%) Injection.

The labeling includes the following information if the complete formula is not specified in the individual monograph: (1) In the case of a liquid preparation, the percentage content of each ingredient or the amount of each ingredient in a specified volume, except that ingredients added to adjust to a given pH or to make the solution isotonic may be declared by name and a statement of their effect; and (2) in the case of a dry preparation or other preparation to which a diluent is intended to be added before use, the amount of each ingredient, the composition of recommended diluent(s) [the name(s) alone, if the formula is specified in the individual monograph], the amount to be used to attain a specific concentration of active ingredient and the final volume of solution so obtained, a brief description of the physical appearance of the constituted solution, directions for proper storage of the constituted solution, and an expiration date limiting the period during which the constituted solution may be expected to have the required or labeled potency if it has been stored as directed.

Containers for Injections that are intended for use as dialysis, hemofiltration, or irrigation solutions and that contain a volume of more than 1 L are labeled to indicate that the contents are not intended for use by intravenous infusion.

Injections intended for veterinary use are labeled to that effect.

The container is so labeled that a sufficient area of the container remains uncovered for its full length or circumference to permit inspection of the contents.

strength and total volume for single- and multiple-dose injectable drug products

The following formats are acceptable for contents of greater than 1 mL:
Total strength/total volume: 500 mg/10 mL
Strength/mL: 50 mg/mL
or
Total strength/total volume: 25,000 Units/5 mL
Strength/mL: 5,000 Units/mL
The following format is acceptable for contents of less than 1 mL: 12.5 mg/0.625 mL

Containers, including the closures, for preparations for injections do not interact physically or chemically with the preparations in any manner to alter the strength, quality, or purity beyond the official requirements under the ordinary or customary conditions of handling, shipment, storage, sale, and use. The container is made of material that permits inspection of the contents. The type of glass preferable for each parenteral preparation is usually stated in the individual monograph. Unless otherwise specified in the individual monograph, plastic containers may be used for packaging injections (see Containers—Plastics 661).

For definitions of single-dose and multiple-dose containers, see Containers in the General Notices and Requirements. Containers meet the requirements under Containers—Glass 660 and Containers—Plastics 661.

Containers are closed or sealed in such a manner as to prevent contamination or loss of contents. Validation of container integrity must demonstrate no penetration of microbial contamination or chemical or physical impurities. In addition, the solutes and the vehicle must maintain their specified total and relative quantities or concentrations when exposed to anticipated extreme conditions of manufacturing and processing, and storage, shipment, and distribution. Closures for multiple-dose containers permit the withdrawal of the contents without removal or destruction of the closure. The closure permits penetration by a needle and, upon withdrawal of the needle, closes at once, protecting the container against contamination. Validation of the multiple-dose container integrity must include verification that such a package prevents microbial contamination or loss of product contents under anticipated conditions of multiple entry and use.

Piggyback containers are usually intravenous infusion containers used to administer a second infusion through a connector of some type or an injection port on the administration set of the first fluid, thereby avoiding the need for another injection site on the patient's body. Piggyback containers are also known as secondary infusion containers.

The use of a black closure system on a vial (e.g., a black flip-off button and a black ferrule to hold the elastomeric closure) or the use of a black band or series of bands above the constriction on an ampul is prohibited, except for Potassium Chloride for Injection Concentrate.

All injectable preparations of neuromuscular blocking agents and paralyzing agents must be packaged in vials with a cautionary statement printed on the ferrules or cap overseals. Both the container cap ferrule and the cap overseal must bear in black or white print (whichever provides the greatest color contrast with the ferrule or cap color) the words: “Warning: Paralyzing Agent” or “Paralyzing Agent” (depending on the size of the closure system). Alternatively, the overseal may be transparent and without words, allowing for visualization of the warning labeling on the closure ferrule.

Containers, including the closures, for dry solids intended for parenteral use do not interact physically or chemically with the preparation in any manner to alter the strength, quality, or purity beyond the official requirements under the ordinary or customary conditions of handling, shipment, storage, sale, and use.

A container for a sterile solid permits the addition of a suitable solvent and withdrawal of portions of the resulting solution or suspension in such manner that the sterility of the product is maintained.

Where the Assay in a monograph provides a procedure for the Assay preparation, in which the total withdrawable contents are to be withdrawn from a single-dose container with a hypodermic needle and syringe, the contents are to be withdrawn as completely as possible into a dry hypodermic syringe of a rated capacity not exceeding three times the volume to be withdrawn and fitted with a 21-gauge needle not less than 2.5 cm (1 inch) in length, with care being taken to expel any air bubbles, and discharged into a container for dilution and assay.

Each container of an injection is filled with sufficient excess of the labeled “size” or that volume which is to be withdrawn. See Injections under Pharmaceutical Dosage Forms 1151.

determination of volume of injection in containers

Single-Dose Containers— Select 1 container if the volume of the container is 10 mL or more, 3 containers if the nominal volume is more than 3 mL and less than 10 mL, or 5 containers if the nominal volume is 3 mL or less. Take up individually the total contents of each container selected into a dry syringe of a 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 its graduated volume. Alternatively, the volume of the contents in mL may be calculated as the mass, in g, divided by the density. For containers with a nominal volume of 2 mL or less, the contents of a sufficient number of containers may be pooled to obtain the volume required for the measurement, provided that a separate, dry syringe assembly is used for each container. The contents 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.

Multi-Dose Containers— For Injections in multiple-dose containers labeled to yield a specific number of doses of a stated volume, select 1 container, and proceed as directed for single-dose containers, using the same number of separate syringe assemblies as the number of doses specified. The volume is such that each syringe delivers not less than the stated dose.

Injections in Cartridges or Prefilled Syringes— Select 1 container if the volume is 10 mL or more, 3 containers if the nominal volume is more than 3 mL and less than 10 mL, or 5 containers if the nominal volume is 3 mL or less. If necessary, fit the containers with the accessories required for their use (needle, piston, syringe) and transfer the entire contents of each container without emptying the needle into a dry tared beaker by slowly and constantly depressing the piston. Determine the volume in mL, calculated as the mass, in g, divided by the density.

Large-Volume Intravenous Solutions— For intravenous solutions, select 1 container. Transfer the contents into a dry measuring cylinder of such a capacity that the volume to be determined occupies at least 40% of the nominal volume of the cylinder. Measure the volume transferred.

Only cautionary statements are to appear on the top (circle) surface of the ferrule or cap overseal of a vial containing an injectable product. A cautionary statement is one intended to prevent an imminent life-threatening situation if the injectable drug is used inappropriately. Examples of such statements include but are not limited to the following: “Warning”, “Dilute Before Using”, “Paralyzing Agent”, “I.M. Use Only”, and “Chemotherapy”.

The text must be in contrasting color and conspicuous under ordinary conditions of use. The cautionary statement may appear solely on the ferrule, provided the cap overseal is constructed so as to allow the cautionary statement beneath the cap to be readily legible.

Identifying numbers or letters, such as code numbers, lot numbers, etc., may appear on the side (skirt) surface of the ferrule on vials containing injectable products. The appearance of such identifying data on the skirt surface of the ferrule, placed where it does not detract from, or interfere with, the cautionary statement on the top surface, should be considered to be a beneficial attribute of the in-process quality control of a product throughout the manufacturing process. Any anticounterfeiting scheme must not detract from or interfere with the cautionary statements.

Under no circumstances would advertising such as company names, logos, or product names be permitted to appear on the top (circle) surface of any ferrule or cap overseal.

The volume of injection in single-dose containers provides the amount specified for parenteral administration at one time and in no case is more than sufficient to permit the withdrawal and administration of 1 L.

Preparations intended for intraspinal, intracisternal, or peridural administration are packaged only in single-dose containers.

Unless otherwise specified in the individual monograph, a multiple-dose container contains a volume of Injection sufficient to permit the withdrawal of not more than 30 mL.

The following injections are exempt from the 1-L restriction of the foregoing requirements relating to packaging:

Injections packaged for intravascular use that may be used for intermittent, continuous, or bolus replacement fluid administration during hemodialysis or other procedures, unless excepted above, must conform to the 1-L restriction.

Injections labeled for veterinary use are exempt from packaging and storage requirements concerning the limitation to single-dose containers and the limitation on the volume of multiple-dose containers.