USP proposes Chapter on Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems

During the last years, leachables and extractables testing became more and more important for the quality of the packaging systems used to store drug products. The suitability of a pharmaceutical packaging system for a drug product can be assessed by extractables and leachables testing. Out of these characterization studies, specific controls for a packaging system, its components, or its materials of construction can be established. The series of general chapters for packaging systems begins with Plastic Packaging Systems and their Materials of Construction <661.1>. This chapter is used to characterize the materials of construction. Plastic Packaging Systems <661.2> is used to characterize the final packaging system and/or component.

Other chapters that will be proposed in the future to address the characterization of plastic materials used in the manufacturing process and medical devices are Plastic Systems Used for Manufacturing Pharmaceutical Products <661.3> and Plastic Medical Devices Used to Deliver or Administer Pharmaceutical Products <661.4>.

Another step in the experts committees activity is the proposal "Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems 1664"published in Pharmacopoial Forum 39(5). This document presents a framework for the design, justification, and execution of a leachables assessment for pharmaceutical packaging and delivery systems. A scientifically sound leachables assessment is important to manufacturers and their various suppliers primarily as a means of establishing the suitability for use of pharmaceutical packaging/delivery systems, as leachables can potentially affect drug product efficacy, safety, and quality. Additionally, such a leachables assessment could provide an understanding of the sources of leachables and how to evaluate and manage leachables during the drug development and manufacturing processes.

The chapter establishes critical dimensions of a leachables assessment and discusses practical and technical aspects of each dimension. It does not establish specific analytical methods or leachables specifications and acceptance criteria for any particular dosage form or packaging system and drug product combination; nor does it delineate every situation in which a leachables assessment is required. It is not possible for a general discussion of drug product leachables to anticipate and cover all situations which can occur in the pharmaceutical industry where a leachables assessment might be required. Designing an individual leachables assessment is a process that strikes a balance between sound science, prudent resource allocation, and effective risk management with an emphasis on patient safety. Achieving this balance is the responsibility and obligation of the drug product manufacturer, and assumes due consideration of applicable legal and regulatory requirements. The principles and best demonstrated practices outlined in this general chapter represent a consensus interpretation of sound science and can therefore be extrapolated and applied to any situation in which a leachables assessment is required for pharmaceutical application.

In many cases, drug product leachables assessments are based on or facilitated by knowledge from extractables assessments accomplished on drug product packaging systems, packaging components, and packaging materials of construction.

The text should be read in conjunction with the chapters Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems <1663> and <1664.1> Orally Inhaled and Nasal Drug Products.

All three documents can be found at the  Pharmacopoeial Forum