This chapter provides general guidance on packaging considerations for Pharmacopeial preparations that may be stored, transported, and distributed. It describes procedures that should be considered to ensure that proper packaging practices are maintained. It does not affect any applicable requirements under good manufacturing practices, state laws governing pharmacy, the USP General Notices and Requirements or monographs, or provisions under approved labeling.

Definitions for storage conditions and packaging are provided in Preservation, Packaging, Storage, and Labeling under General Notices and Requirements. All equipment used for recording, monitoring, and maintaining these temperature and humidity conditions should be calibrated on a regular basis. This calibration should be traceable to national or international standards (see also the general information chapter Monitoring Devices—Time, Temperature, and Humidity 1118).

The monograph packaging and storage statement specifies that the container (primary package) should meet the requirements under Containers 661 and Containers—Permeation 671, which include the stipulations for determining if a container is “tight” or “well-closed.” In most cases, compendial preparations are expected to be packaged in “tight” containers, especially if the article is moisture sensitive. In addition, where necessary, the packaging component should protect the preparation from light, reactive gases, solvent loss, microbial contamination, etc. “Tight” and “well-closed” containers are clearly defined in General Notices and Requirements (see Containers under Preservation, Packaging, Storage, and Labeling), whereas testing protocol and moisture permeation limits to determine if the container meets either of these definitions can be found in Containers 661 and Containers—Permeation 671 for single-unit and multiple-unit containers.

A packaging system is composed of a container system with its closure. This system may include several layers of protection for the Pharmacopeial preparation along with any sealing devices, delivery devices, labeling, and package inserts. The General Notices section also provides definitions for types of packaging systems that contain and protect a Pharmacopeial preparation (e.g., single-unit containers, unit-dose containers, etc.). Stability testing is conducted on the dosage forms packaged in the container–closure system proposed for marketing.

One type of permeation test for multiple-unit containers is described in Containers—Permeation 671. This test is intended for drug products being dispensed on prescription in vials with a container–closure system. The results of the test reflect the water vapor permeation through the container and through the closure. Limits have been established to define whether a container for dispensing has tight or well-closed characteristics with regard to water vapor permeation. FDA recommends that manufacturers perform this test on the container–closure system, although it is not specified in USP. In this particular test, the inner seal of the manufacturer's container–closure system is removed prior to testing.

Single-unit containers for capsules and tablets under Containers—Permeation 671 are measured for water vapor permeation according to the criteria for the four classes of containers (classes A–D).

The USP recognizes several official container materials that can be selected on the basis of their properties. Most containers are made of glass or plastic. Glass containers must be evaluated for chemical resistance and light transmission (if indicated) as described in Containers 661. In addition, injectable medication containers should be reviewed according to the section Packaging under Injections 1. Elastomeric closures should be evaluated separately as described in Elastomeric Closures for Injection 381. Plastic containers should be assessed using different criteria for the three types of plastics as described in the following sections under Containers 661: Polyethylene Containers (PE) for dry oral solid dosage forms, Polyethylene Terephthalate Bottles and Polyethylene Terephthalate G Bottles (PET, PETG) for liquid oral dosage forms, and Polypropylene Containers (PP) for dry solid and liquid oral dosage forms. As articulated in these sections, plastics should undergo testing for light transmission (if appropriate), water vapor permeation (see also Containers—Permeation 671), extraction physiochemical testing, and biological testing (see also Biological Reactivity Tests, In Vitro 87 and Biological Reactivity Tests, In Vivo 88). For example, testing water vapor permeation for a PE container is conducted by sealing the container with heat-sealed foil laminate and measuring the water permeation in a humid atmosphere. Given that water vapor does not permeate the foil laminate, this test assesses only the properties of the container. The level of protection provided by a packaging system marketed with a heat-sealed foil laminate inner seal (prior to removal of the foil) is approximated by this test. However, in the case of a PET bottle for liquid preparations, water vapor permeation testing is done by filling containers with water and measuring the water loss rate in a dry atmosphere. Additional testing may be required for certain pharmaceutical dosage forms as well.

The container–closure system for the storage or shipment of a bulk liquid drug substance is typically plastic, stainless steel, a glass-lined metal container, or an epoxy-lined metal container with a rugged, tamper-resistant closure. Qualification of the container–closure system for these types of preparations includes evaluation for solvent and gas permeation, light transmittance, closure integrity, ruggedness in shipment, protection against microbial contamination through the closure, and compatibility and safety of the packaging components as appropriate (see Containers 661).

Other information on container–closure systems may be found in FDA's Guidance for Industry: Container Closure System for Packaging Human Drugs and Biologics, www.fda.gov.

Packaging for Pharmacopeial articles can be divided into categories according to terminology generally accepted by industry. As mentioned earlier, the General Notices section provides some definitions for different types of containers classified by their characteristics and uses. In addition, the ASTM Committee D10 on packaging publishes terminology, practices, test methods, specifications, guides, and classifications for testing and evaluating packaging (see ASTM D99695, “Standard Terminology of Packaging and Distribution Environments”). Under certain rules and guidelines (e.g., such as 49 CFR, Dangerous Goods, and others), however, alternate terminology is used for the components described below. For terminology pertaining to repackaging processes, refer to Packaging Practice—Repackaging a Single Solid Oral Drug Product into a Unit-Dose Container 1146.

Packaging materials are regulated by a variety of federal, state, and local rules. In general, most pharmaceutical packaging containers can be recycled within local programs. The use of recycled material in primary containers is governed by the FDA, but it is generally not allowed. Pharmaceutical manufacturers commonly follow the most current Coalition of Northeastern Governors' rules (e.g., Model Toxics in Packaging Legislation) regarding heavy metals in packaging and other environmental issues.

Certain classes of Pharmacopeial articles may require special handling. Such articles include products classified as (1) Dangerous Goods under the Department of Transportation (DOT), state, local, or carrier rules; (2) controlled drugs under the Drug Enforcement Administration (DEA); or (3) scheduled substances under state regulations.

The labeling of shipping containers by manufacturers must be in compliance with the pertinent sections of FDA and DOT rules.