Method Validation in Pharmaceutical Analysis E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 718

Veröffentlichungsjahr: 2014

Beschreibung

This second edition of a global bestseller has been completely redesigned and extensively rewritten to take into account the new Quality by Design (QbD) and lifecycle concepts in pharmaceutical manufacturing.

As in the first edition, the fundamental requirements for analytical method validation are covered, but the second edition describes how these are applied systematically throughout the entire analytical lifecycle. QbD principles require adoption of a systematic approach to development and validation that begin with predefined objectives. For analytical methods these predefined objectives are established as an Analytical Target Profile (ATP). The book chapters are aligned with recently introduced standards and guidelines for manufacturing processes validation and follow the three stages of the analytical lifecycle: Method Design, Method Performance Qualification, and Continued Method Performance Verification. Case studies and examples from the pharmaceutical industry illustrate the concepts and guidelines presented, and the standards and regulations from the US (FDA), European (EMA) and global (ICH) regulatory authorities are considered throughout.

The undisputed gold standard in the field.

Leseprobe

Table of Contents

Cover

Related Titles

Title Page

Copyright

Foreword

List of Contributors

Chapter 1: Analytical Validation within the Pharmaceutical Lifecycle

1.1 Development of Process and Analytical Validation Concepts

1.2 Alignment between Process and Analytics: Three-Stage Approach

1.3 Predefined Objectives: Analytical Target Profile

1.4 Analytical Life Cycle

References

Chapter 2: Analytical Instrument Qualification

2.1 Analytical Instrument and System Qualification

2.2 Efficient and Economic HPLC Performance Qualification

Acknowledgment

Abbreviations

References

Chapter 3: Establishment of Measurement Requirements – Analytical Target Profile and Decision Rules

3.1 Introduction

3.2 Defining the Fitness for Intended Use

3.3 Decision Rules

3.4 Overview of Process to Develop Requirements for Procedure Performance

3.5 Decision Rules and Compliance

3.6 Calculating Target Measurement Uncertainty

3.7 Types of Decision Rules

3.8 Target Measurement Uncertainty in the Analytical Target Profile

3.9 Bias and Uncertainty in a Procedure

3.10 ATP and Key Performance Indicators

3.11 Measurement Uncertainty

3.12 Example

3.13 Conclusion

References

Chapter 4: Establishment of Measurement Requirements – Performance-Based Specifications

4.1 Introduction

4.2 Intended Purpose

4.3 Identification

4.4 Assay

4.5 Impurities

4.6 Limit Tests

4.7 Quantitative Tests

4.8 Summary

References

Chapter 5: Method Performance Characteristics

5.1 Introduction

5.2 Precision

5.3 Accuracy and Range

5.4 Specificity

5.5 Linearity

5.6 Detection and Quantitation Limit

5.7 Glossary

5.8 Acknowledgments

References

Chapter 6: Method Design and Understanding

6.1 Method Selection, Development, and Optimization

Acknowledgments

6.2 Analytical Quality by Design and Robustness Investigations

Acknowledgments

6.3 Case Study: Robustness Investigations

Acknowledgments

6.4 System Suitability Tests

References

Chapter 7: Method Performance Qualification

7.1 Introduction

7.2 Case Study: Qualification of an HPLC Method for Identity, Assay, and Degradation Products

7.3 Design and Qualification of a Delivered Dose Uniformity Procedure for a Pressurized Metered Dose Inhaler

Acknowledgment

7.4 Implementation of Compendial/Pharmacopeia Test Procedures

7.5 Transfer of Analytical Procedures

Acknowledgments

References

Chapter 8: Continued Method Performance Verification

8.1 Introduction

8.2 Routine Monitoring

8.3 Investigating and Addressing Aberrant Data

8.4 Continual Improvement

References

Index

End User License Agreement

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Guide

Cover

Table of Contents

Foreword

Chapter 1: Analytical Validation within the Pharmaceutical Lifecycle

List of Illustrations

Figure 1.1

Figure 1.2

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 2.6

Figure 2.7

Figure 2.8

Figure 2.9

Figure 3.1

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Figure 3.6

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Figure 4.1

Figure 4.2

Figure 5.1

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Figure 5.5

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Figure 6.1

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Figure 7.1

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Figure 8.1

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Figure 8.9

Figure 8.10

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Figure 8.14

List of Tables

Table 1.1

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 4.1

Table 5.1

Table 5.2

Table 5.3

Table 5.8

Table 5.4

Table 5.5

Table 5.6

Table 5.7

Table 5.9

Table 5.10

Table 5.11

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Table 5.17

Table 6.1

Table 6.2

Table 6.3

Table 6.4

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Table 6.6

Table 6.7

Table 6.8

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Table 6.27

Table 7.1

Table 7.2

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Table 7.6

Table 7.7

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Table 7.29

Table 8.1

Table 8.2

Table 8.3

Table 8.5

Table 8.6

Table 8.7

Table 8.8

Table 8.9

Table 8.10

Table 8.11

Table 8.12

Table 8.13

Table 8.14

Table 8.15

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Edited by Joachim Ermer and Phil Nethercote

Method Validation in Pharmaceutical Analysis

A Guide to Best Practice

Second, Completely Revised and Updated Edition

Editors

Dr. Joachim Ermer

Sanofi-Aventis Deutschl. GmbH

Industriepark Höchst D710

Quality Control Service / R.202

65926 Frankfurt

Germany

Dr. Phil Nethercote

GSK - GlaxoSmithKline

Shewalton Road

GMS Quality

KA11 5AP Irvine, Ayrshire

United Kingdom

Cover

Background Photo.

Source Fotolia © Alexander Raths

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Foreword

In 2002, FDA began an initiative entitled “Pharmaceutical Quality for the 21st Century.” This initiative identified a number of problems in the pharmaceutical industry: pharmaceutical manufacturing processes often had low efficiencies in comparison to other industry sectors with significant levels of waste and rework, reasons for manufacturing failures were not always understood, the uptake of new technologies was slower than in other sectors, and manufacturing cycle times and costs were high. In September 2004, the FDA published a report “Pharmaceutical cGMPS for the 21st century – A risk based approach” which made a series of recommendations aimed at encouraging the early adoption of new technological advances, facilitating application of modern quality management techniques, encouraging adoption of risk-based approaches, and ensuring that regulatory review and inspection polices were consistent, coordinated, and based on state-of-the art pharmaceutical science. In October 2005, Janet Woodcock of the FDA described the desired state of the pharmaceutical industry as a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight. Between 2005 and 2012, the International Conference for Harmonisation (ICH) developed a series of guidances (ICH Q8,9,10 and 11) that were intended to modernize the pharmaceutical industries approach to Quality Management and embed more scientific and risk-based approaches to pharmaceutical development and manufacturing. This new paradigm was based on a philosophy of “Quality by Design” (QbD). ICHQ8,9,10, and 11 described how systematic approaches to process understanding and control of risk coupled with implementation of effective quality management systems could deliver more robust manufacturing processes.

A critical enabler to ensuring manufacturing processes consistently produce products that are fit for patients and consumers is the analytical data that allows an understanding of the process and confirms the quality of the product produced. Many of the problems and issues with pharmaceutical manufacturing processes uncovered via the FDAs “Pharmaceutical Quality for the 21st Century” initiative were also true for analytical methods used by the industry. Uptake of new analytical technologies was slow, repeat occurrences of out-of-specification results due to lab errors were common, and levels of waste and rework were high. Clearly, analytical testing is simply a “process” in the same way that manufacturing is a process – the difference being that the output of a manufacturing process is a product, while the output from an analytical measurement is data. It follows therefore that it should be possible to apply the QbD principles described in the ICH Q8–Q11 guidances to enhance the understanding, control, and performance of analytical methods.

In the second edition of Method Validation in Pharmaceutical Analysis, the editors have included chapters written by subject matter experts, which illustrate how the QbD principles can be applied to analytical methods. These include the following: how an analytical target profile (ATP) can be established to predefined the objectives for the quality of the data that the method is required to produce (which parallels the concept of a QTPP used to define the quality of product a manufacturing process needs to produce), how the lifecycle approach to process validation developed for manufacturing processes can also be applied to analytical methods, and how the need for effective change and knowledge management process throughout the lifecycle are as equally important for analytical methods as they are for manufacturing processes.

The concepts described in this book reflect modern quality management practices and include approaches used widely in other industries (e.g., measurement uncertainty). The establishment of “fit-for-purpose” criteria in an ATP will facilitate a more scientific and risk-based approach to method validation activities ensuring efficient use of resources that are focused on the areas of highest risk and will bring the pharmaceutical industry in line with other science-based industries. Ultimately, this will help promote regulatory as well as business excellence and public health through the better understanding and control of the measurement of quality of pharmaceutical products.

Moheb Nasr, Ph.D.

VP, CMC Regulatory Strategy, GSK

List of Contributors

Christophe Agut

Biostatistics and Programming

Sanofi R&D, 195

Route d'Espagne

Toulouse Cedex 1 31036

France

Christopher Burgess

Burgess Analytical Consultancy Limited

The Lendings

Startforth

Barnard Castle DL12 9AB

UK

Todd L. Cecil

USP

12601 Twinbrook Parkway

Rockville MD 20852

USA

Joachim Ermer

Sanofi-Aventis Deutschland GmbH

Industrial Quality and Compliance, Frankfurt Chemistry

Room 605/Building D711

Industriepark Höchst

Frankfurt 65926

Germany

Melissa Hanna-Brown

Pfizer Global R&D

Analytical Research and Development

Ramsgate Road

Sandwich

Kent CT13 9NJ

UK

Brent Harrington

Pfizer Global R&D

Analytical Research and Development

Ramsgate Road

Sandwich

Kent CT13 9NJ

UK

Mary Lee Jane Weitzel

Consultant

15 Park Royal Bay

Winnipeg

Manitoba R3P1P2

Canada

Gerd Kleinschmidt

Sanofi-Aventis Deutschland GmbH

R&D LGCR Analytical Sciences

Building H823/Room 206

Industriepark Höchst Frankfurt am Main 65926

Germany

Rosario LoBrutto

TEVA Pharmaceuticals

Pharmaceutical Development (Steriles)

Quaker Road

Pomona NY 10970

USA

R. D. McDowall

McDowall Consulting

Murray Avenue

Bromley

Kent BR1 3DJ

UK

Pauline McGregor

PMcG Consulting

Analytical Services

Ross Lane

Oakville ON L6H 5K6

Canada

Phil Nethercote

GSK – GlaxoSmithKline

GMS Quality

Shewalton Road

Irvine

Ayrshire KA11 5AP

UK

Andy Rignall

AstraZeneca R&D

Pharmaceutical Development

Charter Way

Hurdsfield Industrial Estate

Macclesfield SK10 2NA

UK

Roman Szucs

Pfizer Global R&D

Analytical Research and Development

Ramsgate Road

Sandwich

Kent CT13 9NJ

UK

Hermann Wätzig

Technical University Braunschweig

Institute of Medicinal and Pharmaceutical Chemistry

Beethovenstrasse 55

Braunschweig D-38106

Germany

1Analytical Validation within the Pharmaceutical Lifecycle

Phil Nethercote and Joachim Ermer

1.1 Development of Process and Analytical Validation Concepts

The concept of validation in the pharmaceutical industry was first proposed by two Food and Drug Administration (FDA) officials, Ted Byers, and Bud Loftus, in the mid 1970s in order to improve the quality of pharmaceutical products [1]. Validation of processes is now a regulatory requirement and is described in general and specific terms in the FDA's Code of Federal Regulations – CFR21 parts 210 and 211 as well as in the EMA's Good Manufacturing Practices (GMP) Guide Annex 15. The 1987 FDA guide to process validation [2] defined validation as Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes. While the first validation activities were focused on the processes involved in making pharmaceutical products, the concept of validation quickly spread to associated processes including the analytical methods used to test the products.

Regulatory guidance on how analytical methods should be validated has also existed for some time [3], however, it was not until the establishment of the International Conference on the Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) in 1990 that there was a forum for dialogue between regulatory authorities and industry and one of the first topics within the Quality section was analytical procedure validation. The ICH was very helpful in harmonizing terms and definitions [4a] as well as determining the basic requirements [4b]. Of course, due to the nature of the harmonization process, there were some compromises and inconsistencies.

Table 1.1 shows the ICH view on the required validation characteristics for the various types of analytical procedures.

Table 1.1 Validation characteristics normally evaluated for the different types of test procedures [4a] and the minimum number of determinations recommended [4b]

Validation characteristic

Minimum Number

Analytical procedure

Identity

Impurities

Assay

a

Quantitative