In review of the current and pending requirements for USP qualification testing of a drug or medical device package system, it is evident that the process has become more expansive and stringent over the past 10 years. The days of large molecule tablets stored in 5502BN HDPE containers, or any liquid product being stored in an amber PET bottles are long gone. Many of today’s drug products are biologically based and complex container systems such as pre-filled syringe are more the norm and not the exception. The USP has been working diligently to ensure that the qualification test requirements for the new products and these advanced package systems meet the current and applicable needs especially as it relates to ensuring patient safety. Navigating the requirements of these new and more complex test requirements can be a daunting task. This article will outline and summarize the current applicable USP test methods (chapters) specific to package system qualification testing. This will serve to provide the reader with a foundation or basic guideline of what testing may be applicable to their product package system.
USP 661 Plastic Packaging Systems and Their Materials of Construction
The purpose of this chapter is to provide standards for plastic articles (materials, components, and systems) used to package medical articles (pharmaceuticals, biologics, and dietary supplements).
USP 661.1 Plastic Materials of Construction
This chapter becomes official on December 1, 2025 and will replace the existing USP 661 chapter. The USP is very clear in that early adoption is acceptable and highly encouraged. Similar to current 661, this chapter will provide the qualification test requirements for determining the suitability of plastic materials of construction used in package systems for drug products. The chapter covers a wider variety of plastic types and the testing is more intense and complex in comparison to the 661 chapter.
USP 661.2 Plastic Packaging Systems for Pharmaceutical Use
Like its sister chapter 661.1, this chapter becomes official on December 1, 2025 and will replace the existing USP 661 chapter. In addition, the USP is very clear in that early adoption is acceptable and highly encouraged. Whereas the 661.1 chapter is specific to individual “material of construction”. The 661.2 chapter is applicable to the entire plastic package system taken all together inclusive of closure system. For example, a package system may include an HDPE bottle, with a PP closure, with a foil seal LDPE heat seal. These collective components would be tested as one plastic unit.
USP 671 Container Performance Testing
It is the purpose of this chapter to provide standards for the functional properties of packaging systems used for solid oral dosage forms (SODFs) and liquid oral dosage forms (LODFs). The tests in this chapter may be applied to other dosage forms with the appropriate justification. These tests determine the moisture vapor transmission rate (MVTR) for plastic packaging systems for manufacturers, packagers, and re-packagers. This chapter also includes a classification system that allows pharmacists and institutional re-packagers to select appropriate containers to repackage SODFs and LODFs in. Light percent testing is also covered if the container is intended to prevent light intrusion.
USP 1671 The Application of MVTR for Solid Oral Dosage Forms in Plastic Packaging Systems
This chapter is a supplement and support chapter for USP 671 and it highlights how the test methods have become more complex – a test chapter needs a support chapter to explain how to effectively use and interpret the chapter. This chapter describes the methodology of providing evidence for the moisture barrier equivalency of two similar package systems, defined the upper limit of MVTR for SODF products, offers a comparison of the desiccant to water based methods and explains how to best leverage the MVTR data. A must-read chapter if you are performing USP 671 MVTR testing for plastic package systems holding a SODF.
USP 670 Auxiliary Packaging Components
Auxiliary packaging components are articles that are used to support or enhance container–closure systems. These articles include, but are not limited to, pharmaceutical coil and desiccants for containers.
USP 381 Elastomeric Components in Injectable Pharmaceutical Product Packaging / Delivery Systems
As specifically directed by the USP in this chapter, every elastomeric component used in a pharmaceutical package system should be proven suitable for its intended purpose. This chapter provides the baseline chemical and biological reactivity requirements for the selection of elastomeric injectables package system components. This is the general chapter for elastomeric components that is currently in effect.
USP 1381 Assessment of Elastomeric Components Used in Injectable Product Package Systems
Currently effective, this guidance chapter is a supplement to the current 381 chapter and is intended to provide more detailed color, commentary and direction on elastomeric materials that are being tested to the 381 chapter. In reviewing this general chapter, please pay special attention to how to effectively use it as outlined in the Scope section of the chapter.
USP 1382 Assessment of Elastomeric Functional Suitability for Parenteral Product Systems
Similar to the USP 1381 chapter, USP 1382 which is also currently effective is a further supplement to the current 381 chapter and is intended to provide more detailed color, commentary and direction on elastomeric materials specific to their functional use and the testing required.
USP 382 Elastomeric Component Functional Suitability in Parenteral Product Packaging Systems
The test methods outlined in this chapter will not become official until December 1, 2025 and there is no current statement for early implementation and adoption. The intent of this chapter will be to address the fitness for intended use of the elastomeric components that will be used in parenteral dosage forms and will include all primary package system parts that are completely or partially made of elastomeric material.
USP 660 Containers – Glass
This chapter outlines the qualification requirements for any glass used in the package system that is intended to come into contact with a drug product.
USP 665 Plastic Components / Systems used to Manufacture Drug Products
This new general chapter which id currently in development is not scheduled to become official until May 2, 2026. While not specifically a container or package system chapter, the use of plastic (similar to the use of plastic for container systems) has some carrier over as, for example, the 665 test procedures may be applicable to plastic storage containers used in the manufacturing process.
USP 1178 Good Re-Packaging Processes
This chapter is intended to provide guidance in the repackaging of oral solid drug products with specific information for removal of drug products from their original container–closure system into a new package system for the sale and distribution process.
USP 1079 Risk Mitigation Strategies for the Storage and Transportation of Finished Drug Products
While not necessarily container or package system specific, the concepts and principles outlined in this chapter tend to fall under the direction of the package engineering leads at most pharmaceutical and biotechnology companies.
USP 1661 Evaluation of Plastic Packaging for Pharmaceutical Use & their Materials of Construction
Originally part of the new 661.1 section (661.3) this chapter is designed to provide guidance and direction on addressing how the drug product can chemically interact with their associated packaging systems and/or the system’s plastic materials of construction while the drug product is being manufactured, shipped, stored, and administered.
USP 1663 Assessment of Extractables Associates with Pharmaceutical Packaging Systems
In more common layperson’s terms, this is the first section specific to extractable and leachable testing. This general information chapter presents a framework for the design, justification, and execution of an extractables assessment for pharmaceutical packaging and delivery systems.
USP 1664 Assessment of Drug Product Leachables Associated with Pharmaceutical Package Systems
The sister chapter to USP 1663, this general information chapters provides relevant guidelines on the design and implementation of extractable testing for the leachables discovered during the 1663 testing program.
USP 1207 Package Integrity Evaluations – Sterile Products
Often referred to as Container Closure Integrity Testing (CCIT), this chapter provides guidance on the integrity assurance of nonporous packages intended for sterile pharmaceutical products. Background instruction is provided on the topics of leaks, leakage rate, and package sealing/closure mechanisms. Explanation is given as to how packages that conform to specified leakage limits help to ensure the contained product meets and maintains sterility and relevant physicochemical specifications. The integration of package integrity assurance as a key component of the entire product life cycle is stressed. Guidance in the selection, validation, and use of leak test methodologies as well as package seal quality tests is included. Detailed recommendations are presented in three subchapters
As the only FDA regulated, cGMP contract laboratory that is solely focused and dedicated to container and package system qualification testing, the CS Analytical Team of Experts know and understand all of the testing required for the wide spectrum of container and package systems. In many cases, our team members have played an active role in helping to define these new and improved procedures and performed the bench work to ensure that the actual methods meet their intent in an effective and useful manner. As you work to qualify your current components, or develop new package systems, this article will provide a table of contents of which USP chapters may be relevant to ensure you meet the regulatory requirements. The CS Analytical Team is always standing by to help provide direction or confirmation when required.