Leachables and Extractables Handbook
Safety Evaluation, Qualification, and Best Practices Applied to Inhalation Drug Products
1. Auflage Februar 2012
700 Seiten, Hardcover
Wiley & Sons Ltd
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.
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).
information across both toxicology and pharmaceutical
analysis/development, it is probably most useful for practicing
toxicologists or chemists, providing both a detailed reference to
dip into and a means of better understanding the requirements and
contributions of colleagues working in the other
discipline." (British Toxicology Society, 1 July
2013)
"However, the book is extremely well written and is a
compelling read. The book accomplishes its goal to provide a
state of the art review with respect to mercury . . . The book
serves as an excellent educational resource."
(International Journal of Toxicology, 31 May 2012)
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-year
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 Extractables Working Groups and is a member of
the ELSIE Board of Directors. Dr. Stults is a thirty-three year
member of the ACS.
LEE M. NAGAO is a Senior Science Advisor in the
Pharmaceutical Practice Group at Drinker Biddle & Reath LLP. As
a member of the IPAC-RS Secretariat, Dr. Nagao supports the
Consortium's initiatives in materials quality, leachables and
extractables, supplier quality, and foreign particles. She was a
member of the PQRI OINDP Leachables and Extractables Working Group
and serves as Science Advisor and Secretariat to the ELSIE
Consortium. Dr. Nagao is a member of the ACS and the AAAS.
