Specification of Drug Substances and Products

Development and Validation of Analytical Methods

Christopher M. Riley, Thomas W. Rosanske, George L. Reid, Christopher M. Riley, Thomas W. Rosanske, George L. Reid

• Publisher: Elsevier
• Year: 2020
• eBook ISBN: 9780081028254
• Edition: 2
• Topic: Physical Sciences
• Subtopic: Biotechnology

Specification of Drug Substances and Products: Development and Validation of Analytical Methods, Second Edition, presents a comprehensive and critical analysis of the requirements and approaches to setting specifications for new pharmaceutical products, with an emphasis on phase-appropriate development, validation of analytical methods, and their application in practice. This thoroughly revised second edition covers topics not covered or not substantially covered in the first edition, including method development and validation in the clinical phase, method transfer, process analytical technology, analytical life cycle management, special challenges with generic drugs, genotoxic impurities, topical products, nasal sprays and inhalation products, and biotechnology products. The book's authors have been carefully selected as former members of the ICH Expert Working Groups charged with developing the ICH guidelines, and/or subject-matter experts in the industry, academia and in government laboratories. - Presents a critical assessment of the application of ICH guidelines on method validation and specification setting - Written by subject-matter experts involved in the development and application of the guidelines - Provides a comprehensive treatment of the analytical methodologies used in the analysis, control and specification of new drug substances and products - Covers the latest statistical approaches (including analytical quality by design) in the development of specifications, method validation and shelf-life prediction

Part I

Introduction

Outline

Chapter 1. Introduction

Chapter 2. General principles and regulatory considerations: specifications and shelf life setting

Chapter 3. General principles and regulatory considerations: method validation

Chapter 4. Application of quality by design to the development and validation of analytical methods

Chapter 5. Analytical methods in the clinical phase of development

Chapter 6. Analytical method transfer

Chapter 7. Process analytical technology

Chapter 1: Introduction

Christopher M. Riley ¹ , Thomas W. Rosanske ² , and George L. Reid ^{3 1} Riley and Rabel Consulting Services, Inc., Maryville, MO, United States ² T.W. Rosanske Consulting, Overland Park, KS, United States ³ Cardinal Health Regulatory Sciences, Kansas City, MO, United States

Abstract

The general framework of the previous edition of this book, published in 2014, was based on key quality guidelines ICH guidelines (Q1–Q11) and the relevant multidisciplinary guidelines (M1–M8), along with recent changes in regional regulatory guidelines and compendial requirements. Since then, a number of the ICH guidelines have been revised or updated and new ones related more to the drug development process and life cycle management have been added either in the form of drafts or concept papers Following the model of the previous edition, this book uses the new and updated ICH guidances, regulatory guidances and compendial requirements as the basic framework for the text. Fifteen of the original chapters have been revised and nine new chapters added, divided into seven sections: Introduction (Q1–Q14, M4 and M7), Universal Tests, Specific Tests: Drug Substances, Specific Tests: Drug Product, Biotechnology Products, Pharmacopeial Methods and Biological Fluids

Keywords

Design space; Identification tests; International Council on Harmonisation; Limit tests; Quality guidelines; Quantitative tests

1. References

The previous edition of this book was published in 2014. ¹ The general framework of that book was based on key quality guidelines (Q1–Q11) ^2–26 published by the International Council on Harmonisation (ICH) (then referred to as International Conference on Harmonization), along with regional regulatory guidelines and compendial requirements. Since then, revisions to some published ICH guidelines have occurred, and new guidelines related more to the drug development process and life cycle management have been added (e.g., ICH Q12–Q14) ^27–29 either in the form of drafts or concept papers.

This book edition references the new and updated ICH guidelines, regulatory guidance documents, and compendial requirements as the basic framework for the text. The primary objectives of this book are (1) to capture the many regulatory and technical advances that have occurred in the field since publication of the previous edition, (2) to provide an updated critical and comprehensive assessment of the approaches used to identify the key quality attributes of a drug substance or drug product that impact the safety, efficacy, and manufacturability, (3) to select appropriate analytical techniques based on the sensitivity, accuracy, and precision needed to adequately measure and control the identified quality attributes, and (4) to determine how the analytical methods are developed and validated for their intended use. New chapters, not included in the first edition, ¹ cover analytical methods in the clinical phase of development (Chapter 5), method transfer (Chapter 6), process analytical technology (Chapter 7), mutagenic impurities (Chapter 12), drug release for topical products (Chapter 19), and biotechnology products (Chapters 20 and 21). The previous edition ¹ chapters have been updated.

The ICH Quality Guidelines form the general framework for the application of worldwide marketing submissions and reviews of new drug products. Where the quality (Q1–Q14) ^2–29 and relevant key multidisciplinary (M4, M7–M10) ^30–34 ICH Guidelines fit into the general drug development, framework is shown in Fig. 1.1. The Common Technical Document (CTD, ICH M4) ³⁰ or its electronic version (eCTD, ICH M8) is the generally harmonized document most widely used by the ICH and many non-ICH countries for clinical trial and marketing authorization applications. The ICH Quality Guidelines Q1–Q6 describe most of the general requirements for the analytical content of the CTD and are then followed by a series of guidelines (Q7–Q14) addressing some of the key approaches to drug development and life cycle management that may also be included in the CTD.

According to the ICH definition, the specification of a new drug substance or a drug product (Q6A and Q6B) contains three elements: (1) the quality attributes (or tests), (2) references to the associated methods, and (3) the acceptance criteria. While ICH guidelines on specifications (Q6) and method validation (Q2) describe what information regulators expect to see in a new drug application, they provide very little detail on how the guidelines are to be implemented at the technical level. The absence of specific direction on the implementation of the ICH Quality Guidelines also allows for sponsor-to-sponsor differences, including the application of new and improved analytical technologies (such as process analytical technology) targeted to measuring the critical quality attributes which impact product performance. In keeping with the spirit of the previous edition of this book, this version is not intended as just a review of existing regulatory guidance and industry practices. Rather, in addition to discussing conventional approaches, each chapter will address current and critical issues and novel approaches. The authors have again been carefully selected as being former members of the ICH Expert Working Groups charged with developing the ICH guidelines and/or subject-matter experts from industry, academia, and government laboratories. This book provides the reader not only with an understanding of industry ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Part I. Introduction
• Part II. Universal tests
• Part III. Specific tests: drug substances
• Part IV. Specific tests: Drug product
• Part V. Biotechnology products
• Part VI. Pharmacopeial methods
• Part VII. Biological fluids
• Index