ICH Quality Guidelines

An Implementation Guide

Andrew Teasdale, David Elder, Raymond W. Nims, Andrew Teasdale, David Elder, Raymond W. Nims

• Publisher: Wiley
• Year: 2017
• Print ISBN: 9781118971116
• eBook ISBN: 9781118971130
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

Examining the implications and practical implementation of multi-disciplinary International Conference on Harmonization (ICH) topics, this book gives an integrated view of how the guidelines inform drug development strategic planning and decision-making. • Addresses a consistent need for interpretation, training, and implementation examples of ICH guidelines via case studies
• Offers a primary reference point for practitioners addressing the dual challenge of interpretation and practical implementation of ICH guidelines
• Uses case studies to help readers understand and apply ICH guidelines
• Provides valuable insights into guidelines development, with chapters by authors involved in generating or with experience implementing the guidelines
• Includes coverage of stability testing, analytical method validation, impurities, biotechnology drugs and products, and good manufacturing practice (GMP)

1
ICHQ1A(R2) Stability Testing of New Drug Substance and Product and ICHQ1C Stability Testing of New Dosage Forms

Andy Rignall

AstraZeneca, London, UK

1.1 Introduction

A core part of the medicines development process is an understanding of the chemical and physical behavior of the active ingredient and the medicinal product into which it is incorporated under the storage and usage conditions they are likely to encounter. The International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) stability guidance provides a foundation and framework for this endeavor.

Stability testing was one of the first quality, safety, and efficacy topics harmonized across the ICH territories (Europe, USA, Japan, Canada, and Switzerland) in tripartite guidance. The latest revision of ICHQ1A Stability Testing of New Drug Substances and Products was adopted in 2003 [1]. It forms the parent guideline to a suite of associated guidelines providing more details on recommended stability practice. The guideline provides information on storage conditions and duration and testing requirements that should be used to generate the core stability data package in support of product registration in the ICH regions. To encompass the behavior of different drug delivery platforms and their input drug substances, the guideline contains some flexibility in the requirements. Importantly, the guideline also includes an introductory statement recognizing that alternative stability approaches can be used if scientifically justified. A short annex to the parent stability guideline is embodied in ICHQ1C, which addresses the stability requirements for a new dosage form when an applicant develops a new product variant following an original drug substance and drug product application [2].

As worldwide registration is the goal for many medicinal products, the standardization and simplification of the global supply chain for a new medicine, via harmonized stability and labeling practice, is desirable. While the intent of the guideline is to recommend the data sets required to register new drug substance and products in the three main ICH regions, its content is cited and used much more widely. The ICH guidelines are also referenced in territorial guidance beyond the ICH regions either on a stand‐alone basis or in support of local stability guidance. For example, the World Health Organization (WHO) is a long‐standing observer of the ICH process, leading to the incorporation of much of the content of the ICH into its own stability guidance [3].

The ICH stability guidance not only is intended for registration purposes but also informs stability practice during development, for example, the storage conditions described in the guidance can provide a framework for the development stability protocols used to underwrite the quality, safety, and efficacy of drug product used in clinical studies.

While the guidance embodies a traditional approach to stability protocols, the principles described in terms of the stability performance requirements for pharmaceutical products have also been translated into targets for predictive stability screening tools. These tools can provide assurance that when formal stability studies to support product registration are performed in accordance with ICH guidance, the likelihood of obtaining unexpected results is reduced.

Some stability testing requirements are linked with specific product platforms and are detailed in other guidance. Examples include instructions relating to studies that justify in‐use storage, strategies to demonstrate the suitability of protective secondary packaging, and specific studies to underwrite temperature excursions during storage and transportation.

In the “quality by design” era, where pharmaceutical development practice is guided by science‐ and risk‐based approaches, highlighted in three more recent ICH guidelines on pharmaceutical development [4], risk management [5], and pharmaceutical quality system [6], the focus for stability studies has evolved further to emphasize the importance of generating detailed stability knowledge and understanding. This may include establishing the attributes of the input materials (drug substance and excipient) and any processing parameters that are critical to stability performance. Following identification of the attributes critical to stability, an integrated control strategy should be established to ensure the attributes remain within acceptable limits, thereby assuring that the required stability performance is demonstrated. The use of risk management tools to ensure development activities are focused on the areas that will have the most influence on the control of stability (and therefore quality safety and efficacy) is also a feature.

From a practical perspective, the goal of performing stability testing on products intended for global registration remains challenging, requiring the development of a protocol that will result in a high probability of approval in all major markets. Regions with their own specific stability requirements can make the development of a truly “global” registration protocol more challenging. For example, the guidance on stability study requirements for the registration of drug products in countries forming the ASEAN region of Southeast Asia recommends a different long‐term storage condition compared with the ICH regions [7].

This chapter aims to provide an understanding of the fundamental principles behind stability testing and then demonstrate how the guidance is typically applied during pharmaceuti...

Table of contents

• Cover
• Title Page
• Table of Contents
• List of Contributors
• An Introduction to ICH Quality Guidelines: Opportunities and Challenges
• 1 ICHQ1A(R2) Stability Testing of New Drug Substance and Product and ICHQ1C Stability Testing of New Dosage Forms
• 2 Stability Testing: Photostability Testing of New Drug Substances and Products ICH Q1B
• 3 ICH Q1D: Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products
• 4 ICH Q1E Evaluation for Stability Data
• 5 Q2(R1) Validation of Analytical Procedures: Text and Methodology
• 6 Impurities in New Drug Substances and New Drug Products: ICH Q3A/B: Key Guidelines in the General Impurity Management Process
• 7 ICH Q3C Impurities: Guideline for Residual Solvents
• 8 ICH Q3D Elemental Impurities
• 9 ICH Q4: Pharmacopeial Harmonization and Evaluation and Recommendation of Pharmacopeial Texts for Use in the ICH Regions
• 10 ICH Q5A : Viral Safety of Biotechnology Products
• 11 ICH Q5B Analysis of the Expression Construct in Cell Lines Used for Production of Recombinant DNA‐Derived Protein Products
• 12 ICH Q5C Stability Testing of Biotechnological/Biological Products
• 13 Q5D Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products
• 14 Conduct of Risk Assessments: An Integral Part of Compliance with ICH Q5A and ICH Q5D
• 15 ICH Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Processes: Summary and Analysis of ICH Q5E Guideline
• 16 ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
• 17 ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products
• 18 Process‐Related Impurities in Biopharmaceuticals: A Deeper Dive into ICH Q6B
• 19 ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (APIs)
• 20 Q8(R2): Pharmaceutical Development
• 21 ICH Q9 Quality Risk Management
• 22 ICH Q10 Quality Systems: ICH Q10 Implementation at Genentech/Roche
• 23 ICH Q11: Development and Manufacture of Drug Substance
• 24 ICH M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk
• Index
• End User License Agreement