This chapter provides guidance in the use and application of unit-of-use packaging and is intended for use by drug manufacturers, repackagers, and pharmacists. Suppliers of packages and packaging components may find the information useful, as well.
The General Notices defines a unit-of-use container as one that contains a specific quantity of a drug product that is intended to be dispensed as such without further modification except for the addition of appropriate labeling.
Unit-of-use packaging, when provided by the manufacturer, offers some of the following attractive advantages. (1) A dosage form can be dispensed to a patient in the manufacturer's original container, a practice that recognizes that the suitability of the container has been established on the basis of the manufacturer's stability studies. (2) The counting and repackaging of dosage units in the pharmacy is eliminated, thereby reducing the possibility of human error. (3) The pharmacist is able to affix the label for the patient onto the unit-of-use package and is free to use the manufacturer's expiration date as the beyond-use date. (4) The number of dosage units in a single unit-of-use package may be determined on a case-by-case basis. (5) Patient compliance is improved. (6) The unit-of use package can protect against counterfeiting because traceability of product is ensured through bar coding techniques and NDC numbers.
Unit-of-use packaging, when provided by repackagers, offers the same attractive advantages as those offered by the manufacturer. However, unit-of-use repackagers should conform to all requirements as presented in Good Repackaging Practices 1178. There are a number of reasons why repackagers produce unit-of-use packaging: for example, (1) requests from institutions, (2) better inventory control, (3) reduced dispensing times, and (4) variations in some drug therapies.
The packaging of a unit-of-use system may be a multiple container or a single-unit container. A unit-of-use system may contain a drug product in a liquid, semisolid, or solid dosage form (see also FDA Guidance for Industry on Container Closure Systems for Packaging Human Drugs and Biologics). [noteThe terms unit-of-use package and unit-of-use container may be used interchangeably.]
The Poison Prevention Packaging Act (PPPA) of 1970 requires in certain cases the use of special packagingchild-resistant and senior-friendly. Child-resistant packaging protects children from serious injury or illness resulting from ingesting or handling hazardous products including drugs.
Because drugs packaged in unit-of-use packaging are intended to be dispensed to the consumer without repackaging by the pharmacist, the manufacturer or repackager is responsible for the special packaging of PPPA-regulated substances in unit-of-use containers (l6 CFR 1701.1).
TYPES OF CONTAINERS FOR UNIT-OF-USE
Unit-of-use containers are required to be child-resistant if they are intended to be dispensed directly to the patient pursuant to a prescription. Unit-of-use packaging intended for institutional or hospital use may or may not be required to be child-resistant. Unit-of-use containers that are child-resistant single-unit containers include supported blisters, such as separate, peel, push, and tear notch, and enclosed or in-card blisters, such as pull tabs and slide packs. Blister packaging is discussed in the general chapter Packaging PracticeRepackaging a Single Solid Oral Drug Product into a Unit-Dose Container 1146. Unit-of-use containers that are multiple-unit containers include glass and plastic containers.
A single-unit container is one that is designed to hold a quantity of drug product intended for administration as a single dose or a single finished device intended for use promptly after the container is opened. Preferably, the immediate container and/or the outer container or protective packaging shall be so designed as to show any evidence of tampering with the contents. Each single-unit container shall be labeled to indicate the identity, quantity, and/or strength, name of the manufacturer, lot number, and expiration date of the article.
A unit-dose container is a single-unit container for articles intended for administration by other than the parenteral route as a single dose, directly from the container.
A single-dose container is a single-unit container for articles intended for parenteral administration only. It is labeled as such.
A multiple-unit container is a container that permits withdrawal of successive portions of the contents without changing the strength, quality, or purity of the remaining portion.
PACKAGING FABRICATION MATERIALS
Packaging fabrication materials include substances used to manufacture packaging containers such as glass, plastics (including high-density polyethylene (HDPE), low-density polyethylene (LDPE), polyethylene terephthalate, polyethylene terephthalate G and polypropylene (PP), other resins, and other materials as listed in the general test chapter ContainersGlass 660, ContainersPlastics 661, and in the FDA Guidance for Industry on Container Closure Systems for Packaging Human Drugs and Biologics.
Any glass packaging material used in the immediate container should meet the glass test requirements for Limits for Glass Types and Chemical ResistanceGlass Containers: Powdered Glass Test, Water Attack at 121, and Arsenic under general test chapter ContainersGlass 660.
Any plastic packaging material used in the immediate container should meet the plastic test requirements for Plastics in the general test chapters ContainersPlastics 661 and ContainersPerformance Testing 671. Depending on the type of plastic packaging material used, the packaging material meets the requirements for Biological TestsPlastics and Other Polymers, Physicochemical TestsPlastics, Polyethylene Containers, Polyethylene Terephthalate Bottles and Polyethylene Terephthalate G Bottles, and Polypropylene Containers under general test chapter ContainersPlastic 661.
The test for moisture vapor transmission may be carried out as described in the general test chapter ContainersPerformance Testing 671 for multiple-unit and unit-dose containers.
PACKAGING CLOSURE TYPES
Reclosables and nonreclosables may be used for solid, semisolid, and liquid dosage forms. Both must be packaged in compliance with the 16 CFR 1700.15 standards.
Reclosables are containers with suitable closures that may incorporate tamper evidence and child-resistance capabilities. Reclosables may be used for glass or plastic containers.
Nonreclosables are containers with closures that are nonreclosable, such as blisters, sachets, strips, and other single-unit containers. Nonreclosables may include packs such as cold-formed foil blisters, foil strip packs, and PVC/Aclar combining multilayer materials that are thermo-formed or cold-formed foil blisters (see Packaging PracticeRepackaging a Single Solid Oral Drug Product into a Unit-Dose Container 1146). Nonreclosables may be child resistant depending on the intended use and place of use. Household nonreclosables are subject to the PPPA as defined in 16 CFR 1700.14. However, because of some unit-dose designs, not all unit-dose packages comply with the PPPA.
The unit-of-use containers are labeled to include expiration dates, the manufacturer's lot number, the NDC designation, and bar codes as provided in the Labeling section of the General Notices and Requirements under Preservation, Packaging, Storage, and Labeling and in Good Repackaging Practices 1178. Some of the advantages of having bar codes on the label include reduced medication errors, improved inventory control, and improved access to medication identity. The labeling covers information placed in the container by the manufacturer (see General Notices and Requirements). Acceptable labeling can range from the full labeling as for multiple-unit containers to an abbreviated labeling when the container is too small to include all the text. Full labeling may also be provided on the carton if it is not present on the immediate container.
REPACKAGING AND REPROCESSING
Unit-of-use containers are reprocessed or repackaged as instructed by the manufacturer or as directed in the general test chapters ContainersGlass 660 and ContainersPlastics 661 or in the general information chapter Packaging PracticeRepackaging a Single Solid Oral Drug Product into a Unit-Dose Container 1146. A unit-of-use package that is a blister package may not be reprocessed by a pharmacist once it has been deblistered from a unit-dose container (see General Notices and Requirements for application of the appropriate beyond-use date for a multiple-unit or unit-dose container). Deblistering is the process of removing medication from a blister-type container. However, under current Good Manufacturing Practices (cGMPs) and tight quality controls, the manufacturer or contract repackager may repackage and reprocess unit-of-use containers.
INFORMATION FROM MANUFACTURERS
The manufacturer should provide appropriate stability information that can be used to determine appropriate labeling, storage, and shipping statements that will properly inform patients and practitioners. The manufacturer may make other assurances based on product information on packaging and distribution arrangements. In the event that a product is not to be repackaged, the manufacturer may so state in the labeling. The manufacturer also includes labeling and information suitable for optimal handling by the practitioner and the patient. The labeling and information should be bar coded to eliminate medication error and promote medication traceability.
RESPONSIBILITY OF THE DISPENSER
The labeling on a unit-of-use container also includes a label added at the dispensing stage by the pharmacist. Prior to dispensing the unit-of-use package, the dispenser shall add label(s) that provide the following information:
In the pharmacy setting, pharmacists are encouraged to use bar codes, in conjunction with computerized prescription orders, to confirm that the right drug is being dispensed to the right patient. Bar coding would minimize errors and create opportunity for medication traceability and accountability.
Information to Patient
Patients must be given information that applies to the specific prescription being dispensed.
QUALITY CONTROL OF PACKAGING SYSTEM
The packaging system shall meet the general considerations for system suitability, protection, safety, and performance characteristics as described in FDA Guidance for Industry on Container Closure Systems for Packaging Human Drugs and Biologics, in the general test chapters ContainersGlass 660, ContainersPlastics 661, and ContainersPerformance Testing 671, and in the general information chapter Packaging PracticeRepackaging a Single Solid Oral Drug Product into a Unit-Dose Container 1146.