USP Packaging Standards—Strategy and Overview

INTRODUCTION

Since 1820, the US Pharmacopeial Convention (USP) has established compendial standards for drugs sold and marketed in the United States. These standards are published in the USP–NF, which is recognized as the official compendia in the United States.

Drug products and their ingredients are manufactured, packaged, stored, and delivered using packaging/delivery systems. Interactions between a drug product and its packaging/delivery systems can affect the quality of the drug product and/or the packaging system itself. These interactions can be additive, reductive, or transformative. The magnitude of these interactions must not be such that the interactions adversely affect the suitability of the drug product or the packaging/delivery system. Suitability for use of the packaged drug product includes quality and performance aspects such as efficacy, stability, purity, and compendial compliance.

The packaging system’s suitability for use, as determined by the impact of interactions between a drug product and its packaging, is assessed and established via appropriate testing of the packaging material, component, and system.

The USP General Chapters—Packaging and Distribution (GCPD) Expert Committee is responsible for developing new and revising current USP packaging standards. Since the beginning of the 2010–2015 revision cycle, the Expert Committee has worked to delineate a general chemistry-based testing approach for establishing the suitability of packaging materials, components, and systems. The purpose of this article is to provide insight into, and a rationale for, the current thinking and approach of the GCPD Expert Committee on standards for packaging systems.

GENERAL PRINCIPLES

Packaging/delivery systems are constructed from materials and components that can interact with a drug product that contacts these systems at any point in the product’s life cycle. In general, the materials of construction most commonly used in these systems include glass, metals, plastics, and elastomers. Thus, standards that address the suitability of a packaging system with a drug product must consider the quality of these diverse materials and should include relevant test methods and acceptance criteria. The GCPD Expert Committee has recently revised Plastic Packaging Systems and Their Materials of Construction 〈661〉 (1). The rationale behind the development of 〈661〉 will provide insight into the development of plastic packaging systems and the approach to the revision of Elastomeric Closures for Injections 〈381〉 (2), Containers—Glass 〈660〉 (3), and the development of Containers—Metals 〈662〉(4).

In addition, the GCPD Expert Committee will develop an informational general chapter to provide background, support, and an explanation for the requirements presented in each general packaging chapter. For example, Evaluation of Plastic Packaging Systems and Their Materials of Construction with Respect to Their User Safety Impact 〈1661〉 (5) has been developed to support plastic packaging/delivery systems in the 〈661〉 suite of chapters.

Given the complex nature of packaging/delivery systems and their manufacturing processes, multiple testing procedures are needed to establish their suitability with a specific drug product. Furthermore, simply testing the plastic system itself may not be the most effective way to establish its suitability. When considering packaging/delivery systems, an important first step is to ensure the materials and components selected are suitable for their intended use.

Testing materials of construction and components for attributes that are relevant to their suitability provides a basis for selecting the material/component and designing a packaging system. Proper selection minimizes the risk that a packaging system made from those materials or components will be unsuitable. Selecting materials and components that have the propensity to be safe will increase the likelihood that packaging/delivery systems made from those materials and components will be safe.

Taking these points into account, an effective process for establishing a packaging system's suitability for use includes characterizing its materials and components, characterizing the system, and testing the packaged drug product. Characterizing the system, the intermediate step is useful and necessary to bridge the risk assessment gap between materials/components and finished product testing.

Materials undergo considerable stress such as exposure to high temperatures while they are being converted into components. Furthermore, processing aids and additional additives may be introduced during manufacturing. Thus, the extractables profile of a packaging/delivery system is likely to be different from and potentially more complex than the sum of the extractables’ profiles of its materials of construction and components. Therefore, the initial risk assessment of the material and component during selection is appropriately revisited by testing and qualifying the overall packaging/delivery system itself.

Information about a packaging system's extractables can be used to optimize finished drug product testing for leachables, in the case when extractables and leachables testing is necessary. Considering the potential quality and/or safety or impact of extractables may facilitate the identification of leachables that might adversely affect product quality. Such leachables of potential concern would be targeted analytes in the testing of a final drug product. The targeting of specific leachables, as opposed to the screening of drug products for unspecified leachables, has significant analytical benefits, including the ability to develop, validate, and utilize test procedures that are sensitive, specific, and accurate.

Extractables (and their accumulation levels in extracts) can be predictive of the levels of leachables in the drug product, depending on how well the extraction conditions mimic the drug product's actual conditions of use. The GCPD Expert Committee has developed two new general information chapters, Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems 〈1663〉 (6) and Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems 〈1664〉 (7) to assist in the understanding of and approach to establishing extractables and leachables.

In the process of determining a packaging/delivery system’s suitability, three stages exist: material/component characterization, packaging/delivery system characterization, and drug product characterization. Although such a process establishes the general strategy for suitability for use, it lacks the details establishing how to perform such an assessment. These details are outlined in applicable and general information chapters that the GCPD Expert Committee intends as a means for qualifying a packaging system’s suitability for use.

plastic pharmaceutical packaging