Leachables and Extractables Handbook Safety Evaluation, Qualification, and Best Practices Applied to Inhalation Drug Products

by Ball, Douglas J.; Norwood, Daniel L.; Stults, Cheryl L. M.; Nagao, Lee M.

• ISBN13: 9780470173657
• ISBN10: 0470173653
• Edition: 1st
• Format: Hardcover
• Copyright: 2012-01-24
• Publisher: Wiley

Summary

Because leachables are non-drug-related impurities, there is an increased concern for human risk by inhaling them on a daily basis. Recently, however, safety thresholds for leachables have been developed by the FDA, academia, and industry. This book addresses concepts, background, historical use, and development of safety thresholds and their utility for qualifying leachables in Orally Inhaled and Nasal Drug Products (OINDP). Coverage includes the FDA and EU regulatory perspectives concerning leachables in OINDP. While written specifically for OINDP, the principles outlined can be applied to leachables qualification in other drug products.

Author Biography

Douglas J. Ball is a board-certified toxicologist (Diplomate of the American Board of Toxicology) and currently employed by Pfizer Inc. as a Research Fellow in drug safety R D specializing in regulatory strategy and compliance. He chairs the Extractables and Leachables Safety Information Exchange (ELSIE) Board of Directors, and the Toxicology Team of the Product Quality Research Institute (PQRI) leachables and Extractables Working Group for both OINDP and parenteral and ophthalmic drug products. Daniel L. Norwood is a Distinguished Research Fellow in Analytical Development at Boehringer Ingelheim and has more than thirty-five years of professional experience. He chaired the PQRI Leachables and Extractables Working Group and is a thirty-two-years member of the American Chemical Society (ACS). Dr. Norwood is a member of the ELSIE Board of Directors. Cheryl L. M. Stults is a Senior Fellow at Novartis Pharmaceuticals Corporation, focusing on materials analysis and characterization. She chairs the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) Materials and Leachables and Ectractables Working Groups and is a member of the ELSIE Board of Directors. Dr. Stults is a thirty-three years member of the ACS. Lee M. Nagao is a Senior Advisor in the Pharmaceutical Practice Group at Drinker Biddle Reath LLP. As a member of the IPAC-RS Secretariat. Dr. Nagao supports the Consortiums initiatives in materials quality, leachables and ectractables, supplier quality, and foreign particles. She was a member of the PQRI OINDP Leachables and Ectractables Working Group and serves as Science Advisor and Secretariat to the ELSIE Consortium. D. Nagao is a member of the ACS and the AAAS.

Table of Contents

Acknowledgements	p. xi
Dedicationn	p. xiii
Preface	p. xv
Development of Safety Thresholds, Safety Evaluation, and Qualification of Extractables and Leachable in Orally Inhaled Nasal Drug Products
Overview of Leachables and Extractables in Orally Inhaled and Nasal Products	p. 3
A General Overview of the Suitability for Intended Use Requirements for Materials Used in Pharmaceutical Systems	p. 21
Concepts and Application of Safety Thresholds in Drug Development	p. 37
The Development of Safety Thresholds for Leachables on Orally Inhaled and Nasal Drug Products	p. 45
The Analytical Evaluation Thresholds AET) and its Relationship to Safety Thresholds	p. 59
Safety Thresholds in the Pharmaceutical Development Process for OINDP: An Industry Perspective	p. 79
The Chemistry and Toxicology Partnership: Extractables and Leachables Information Sharing Among the Chemists and Toxicologists	p. 93
Use of Safety Thresolds in the Pharmaceutical Development Process for OINDP: US Regulatory Perspectives	p. 117
The Application of Safety Thresholds to Quality Leachables from Plastic Container Closure Systems Intended for Pharmaceutical Products: A Regulatory Perspective	p. 129
Best Practices for Evaluation and Management of Extractables and Leachables in Orally Inhaled and Nasal Drug Products
Analytical Best Practices for the Evaluation and Management of Extractables and Leachables in Orally Inhaled and Nasal Drug Products	p. 155
Chemical and Physical Attributes of Plastics and Elastomers: Impact on the Extractables Profile of Container Closure Systems	p. 185
Pharmaceutical Container Closure System - Selection & Qualification of Materials	p. 217
Analytical Techniques for Identification of Extractables and Leachables	p. 241
Extractables - The Controlled Extraction Study	p. 289
Extractables - Case Study of a Sulfur Elastomer	p. 331
Extractables - Case Study of a Polypropylene	p. 387
Leachables - Analytical Leachables Studies	p. 417
Development and Optimization of Methods for Routine Testing	p. 449
Critical Component Quality Control and Specification Strategies	p. 507
Inorganic Leachables	p. 549
Foreign Particulate Matter	p. 573
Appendixes	p. 617
Experimental Protocol for controlled Extraction Studies on Elastomeric Test Articles	p. 617
Experimental Protocol for controlled Extraction Studies on Plastic Test Articles	p. 630
Protocol Addition, Phase 2 Studies: Quantitative Controlled Extraction Studies on The Sulfur-Cured Elastomer	p. 643
Protocol Addition, Phase 2 Studies: Quantitative Extractables Studies on Sulfur-Cured Elastomer and Polypropylene	p. 656
Index	p. 669
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