Perspectives on the PQRI Extractables and Leachables "Safety Thresholds and Best Practices" Recommendations for Inhalation Drug Products

Recommendation

7/8 May 2024

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The PDA Journal of Pharmaceutical Science and Technology September/October 2013 issue revisited the interesting topic of Leachables and Extractables Testing with three articles. The first article covers the history and development of the PQRI (Product Quality Research Institute's) and is entitled "Perspectives on the PQRI Extractables and Leachables "Safety Thresholds and Best Practices" Recommendations for Inhalation Drug Products. The second is about "The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP)". The third article is a study about "Extractables Characterization for Five Materials of Construction Representative of Packaging Systems Used for Parenteral and Ophthalmic Drug Products".

Following you will find short abstracts of all three articles.

1. Perspectives on the PQRI Extractables and Leachables “Safety Thresholds and Best Practices” Recommendations for Inhalation Drug Products by Daniel L. Norwood, Lee M. Nagao, and Cheryl L. M. Stults (Article Link)

"This commentary presents the history and evolution of this recommendation document starting from the propellant changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose inhaler drug products, which helped prompt interest in inhalation drug product leachables, through the work process of the PQRI group. The overall positive acceptance of the PQRI recommendations is discussed, along with a brief summary of regulatory initiatives influenced by the recommendations. Also presented and discussed are certain key issues and questions that have arisen since the recommendation document was released. The extension and application of best practice recommendations to other high risk drug product types (e.g., large and small volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic Drug Product Working Group, is introduced and considered."

2. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP) by Diane Paskiet, Dennis Jenke, Douglas Ball, Christopher Houston, Daniel L. Norwood, and Ingrid Markovic (Article Link)

"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."

3. Extractables Characterization for Five Materials of Construction Representative of Packaging Systems Used for Parenteral and Ophthalmic Drug Products by Dennis Jenke, James Castner, Thomas Egert, Tom Feinberg, Alan Hendricker, Christopher Houston, Desmond G. Hunt, Michael Lynch, Arthur Shaw, Kumudini Nicholas, Daniel L. Norwood, Diane Paskiet, Michael Ruberto, Edward J. Smith, and Frank Holcomb (Article Link)

"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."