The Product Quality Research Institute Leachables and Extractables Working Group includes pharmaceutical development scientists representing industry, government, and academia. The Working Group was created and constituted to address scientific and regulatory questions concerning the pharmaceutical development process for Orally Inhaled and Nasal Drug Products (OINDP) related to organic extractables and leachables. This effort has resulted in the creation of a detailed "Recommendation Document", which was submitted to the U.S. FDA for consideration in September 2006. The recommendations include proposed safety and analytical thresholds for leachables and extractables, as well as detailed "best practice" recommendations for various aspects of the OINDP pharmaceutical development process, including: materials selection for OINDP container closure system components, Controlled Extraction Studies, Leachables Studies, and Routine Extractables Testing. The Working Group's processes and the detailed and comprehensive recommendations that resulted from those processes, demonstrate that the Product Quality Research Institute collaborative process can result in consensus science-based and data driven recommendations that could have a positive effect on patient care. It is anticipated that the Working Group's recommendations will also contribute to the new "Quality by Design" pharmaceutical development paradigm. This commentary summarizes the best practice recommendations within the context of an overall pharmaceutical development process.

Plastic and rubber materials are commonly encountered in medical devices and packaging/delivery systems for drug products. Characterizing the extractables from these materials is an important part of determining that they are suitable for use. In this study, five materials representative of plastics and rubbers used in packaging and medical devices were extracted by several means, and the extracts were analytically characterized to establish each material's profile of extracted organic compounds and trace element/metals. This information was utilized to make generalizations about the appropriateness of the test methods and the appropriate use of the test materials.

The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a systematic and science-based approach to identify and qualify leachables, including the concept of safety thresholds. Concepts from this widely accepted approach, formally publicized in 2006, are being extrapolated to parenteral and ophthalmic drug products. This article provides an overview of extractables and leachables in drug products and biologics and discusses the PQRI Work Plan and Protocols developed by the PQRI Parenteral and Ophthalmic Drug Products Leachables and Extractables Working Group.

Evaluating a particle profile for parenteral drug products is a well-known challenge due to inevitable variability of results with limited accuracy to actual particle levels present in the product, especially in the subvisible particulate (SbVP) range. It is important to understand the appropriate SbVP counting/ characterization technology, methodology capability, and the particle source (intrinsic or extrinsic). Elastomeric closures are prevalent in many types of drug product container closure systems and are a known source of particle contribution. These components need to be considered when establishing a drug product particle profile. In this work, we describe available particle extraction methodology and its applicability in the analysis of elastomeric closure components using multiple detection technologies. Optimum sample preparation and analytical techniques were established to evaluate submicron particle and SbVP loads from elastomeric closure components. In addition, the impact of stopper siliconization and polysorbate 80 interaction on the degree of SbVPs in the final drug product was assessed.

Combination products (CPs), designated by the US Food and Drug Administration, continue to be on the rise, from the innovation of novel medicines and greater demand for injectable home and selfadministration. CP qualification, its constituent parts or intended use, will depend upon the regulatory jurisdiction with reference to the product's primary mode of action. In the case of a drug product combined with a device, a consult or collaborative review process involving different Centers within the US Food and Drug Administration may be necessary. Policies and practices from different legislative branches of government will need to be merged for a single application. This presents a challenge for aligning information for the application dossier as it relates to a drug master file or drug-device CP design history file. A common objective for both pharmaceuticals and devices is to identify and evaluate patient risks to be mitigated, controlled, and managed across the drug product lifecycle. These concepts are reflected in the regulatory practices of pharmaceutical quality by design and device design controls. Early stakeholder engagement with this dynamic process between different regulatory paradigms becomes an advantage. This manuscript describes aspects for early planning for injectable drug-device development to facilitate time to market with patient centric solutions.