Leachables and Extractables Handbook

A practical and science-based approach for addressing toxicological concerns related to leachables and extractables associated with inhalation drug products Packaging and device components of Orally Inhaled and Nasal Drug Products (OINDP) such as metered dose inhalers, dry powder inhalers, and nasal sprays pose potential safety risks from leachables and extractables, chemicals that can be released or migrate from these components into the drug product. Addressing the concepts, background, historical use, and development of safety thresholds and their utility for qualifying leachables and extractables in OINDP, the Leachables and Extractables Handbook takes a practical approach to familiarize readers with the recent recommendations for safety and risk assessment established through a joint effort of scientists from the FDA, academia, and industry. Coverage includes best practices for the chemical evaluation and management of leachables and extractables throughout the pharmaceutical product life cycle, as well as: Guidance for pharmaceutical professionals to qualify and risk-assess container closure system leachables and extractables in drug products Principles for defining toxicological safety thresholds that are applicable to OINDP and potentially applicable to other drug products Regulatory perspectives, along with an appendix of key terms and definitions, case studies, and sample protocols Analytical chemists, packaging and device engineers, formulation development scientists, component suppliers, regulatory affairs specialists, and toxicologists will all benefit from the wealth of information offered in this important text.

A practical and science-based approach for addressingtoxicological concerns related to leachables and extractablesassociated with inhalation drug productsPackaging and device components of Orally Inhaled and Nasal DrugProducts (OINDP)--such as metered dose inhalers, dry powderinhalers, and nasal sprays--pose potential safety risks fromleachables and extractables, chemicals that can be released ormigrate from these components into the drug product. Addressing theconcepts, background, historical use, and development of safetythresholds and their utility for qualifying leachables andextractables in OINDP, the Leachables and Extractables Handbooktakes a practical approach to familiarize readers with the recentrecommendations for safety and risk assessment established througha joint effort of scientists from the FDA, academia, and industry.Coverage includes best practices for the chemical evaluation andmanagement of leachables and extractables throughout thepharmaceutical product life cycle, as well as:* Guidance for pharmaceutical professionals to qualify andrisk-assess container closure system leachables and extractables indrug products* Principles for defining toxicological safety thresholds that areapplicable to OINDP and potentially applicable to other drugproducts* Regulatory perspectives, along with an appendix of key terms anddefinitions, case studies, and sample protocolsAnalytical chemists, packaging and device engineers, formulationdevelopment scientists, component suppliers, regulatory affairsspecialists, and toxicologists will all benefit from the wealth ofinformation offered in this important text.

Acknowledgements.Dedication.Preface.Part I. Development of Safety Thresholds, Safety Evaluation,and Qualification of Extractables and Leachable in Orally InhaledNasal Drug Products.1. Chapter 1. Overview of Leachables and Extractables in OrallyInhaled and Nasal Products (Douglas J. Ball, Daniel L. Norwood,Lee M. Nagao).2. Chapter 2. A General Overview of the Suitability for IntendedUse Requirements for Materials Used in Pharmaceutical Systems(Dennis Jenke).3. Chapter 3. Concepts and Application of Safety Thresholds inDrug Development (David Jacobson-Kram and Ronald D.Snyder).4. Chapter 4. The Development of Safety Thresholds forLeachables on Orally Inhaled and Nasal Drug Products (W. MarkVogel).5. Chapter 5. The Analytical Evaluation Thresholds (AET) and itsRelationship to Safety Thresholds (Daniel L. Norwood, James O.Mullis, Scott Pennino).6. Chapter 6. Safety Thresholds in the PharmaceuticalDevelopment Process for OINDP: An Industry Perspective (DavidAlexander and James Blanchard).7. Chapter 7. The Chemistry and Toxicology Partnership:Extractables and Leachables Information Sharing Among the Chemistsand Toxicologists (Cheryl L. M. Stults, Ronald Wolff, Douglas J.Ball).8. Chapter 8. Use of Safety Thresolds in the PharmaceuticalDevelopment Process for OINDP: US Regulatory Perspectives(Timothy J. McGovern).9. Chapter 9. The Application of Safety Thresholds to QualityLeachables from Plastic Container Closure Systems Intended forPharmaceutical Products: A Regulatory Perspective (KumudiniNicholas).Part 2. Best Practices for Evaluation and Management ofExtractables and Leachables in Orally Inhaled and Nasal DrugProducts.10. Chapter 10. Analytical Best Practices for the Evaluation andManagement of Extractables and Leachables in Orally Inhaled andNasal Drug Products (Dan Norwood, Cheryl Stults and LeeNagao).11. Chapter 11. Chemical and Physical Attributes of Plastics andElastomers: Impact on the Extractables Profile of Container ClosureSystems (Michael A Ruberto and Diane Paskiet).12. Chapter 12. Pharmaceutical Container Closure System -Selection & Qualification of Materials (Douglas J. Ball,William P. Beierschmitt, and Arthur J. Shaw).13. Chapter 13. Analytical Techniques for Identification ofExtractables and Leachables (Dan Norwood, Thomas N. Feinberg,James O. Mullis, and Scott Pennino).14. Chapter 14. Extractables - The Controlled ExtractionStudy (Thomas N. Feinberg, Daniel L. Norwood, Alice T. Granger,and Dennis Jenke).15. Chapter 15. Extractables - Case Study of a SulfurElastomer (Daniel L. Norwood, Fenghe Qiu, James Coleman, JamesO. Mullis, Alice T. Granger, Keith McKellop, Michelle Raikes, JohnRobson, David Olenski, John Hand, Sr., Melinda K. Munos, TianjingDeng, Xiaochun Yu, Derek Wood, Shauang Li, Song Klapoetke andXiaoya Ding).16. Chapter 16. Extractables - Case Study of aPolypropylene (Diane Paskiet, Laura Stubbs, and Alan D.Hendricker).17. Chapter 17. Leachables - Analytical Leachables Studies(Andrew D. Feilden and Andy Rignall).18. Chapter 18. Development and Optimization of Methods forRoutine Testing (Cheryl L. Stults and Jason M. Creasey).19. Chapter 19. Critical Component Quality Control andSpecification Strategies (Terrence Tougas, Suzette Roan, andBarbara Falco).20. Chapter 20. Inorganic Leachables (Diane Paskiet, ErnestL. Lippert, Brian D. Mitchell, and Diego Zurbriggen).21. Chapter 21. Foreign Particulate Matter (James Coleman,John A. Robson, John A. Smoliga, and Cornelia B.Field).