Pharmaceutical Quality by Design E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Serie: Advances in Pharmaceutical Technology
• Sprache: Englisch

Seitenzahl: 630

Veröffentlichungsjahr: 2018

Beschreibung

A practical guide to Quality by Design for pharmaceutical product development

Pharmaceutical Quality by Design: A Practical Approach outlines a new and proven approach to pharmaceutical product development which is now being rolled out across the pharmaceutical industry internationally. Written by experts in the field, the text explores the QbD approach to product development. This innovative approach is based on the application of product and process understanding underpinned by a systematic methodology which can enable pharmaceutical companies to ensure that quality is built into the product.

Familiarity with Quality by Design is essential for scientists working in the pharmaceutical industry. The authors take a practical approach and put the focus on the industrial aspects of the new QbD approach to pharmaceutical product development and manufacturing. The text covers quality risk management tools and analysis, applications of QbD to analytical methods, regulatory aspects, quality systems and knowledge management. In addition, the book explores the development and manufacture of drug substance and product, design of experiments, the role of excipients, multivariate analysis, and include several examples of applications of QbD in actual practice. This important resource:

• Covers the essential information about Quality by Design (QbD) that is at the heart of modern pharmaceutical development
• Puts the focus on the industrial aspects of the new QbD approach
• Includes several illustrative examples of applications of QbD in practice
• Offers advanced specialist topics that can be systematically applied to industry

Pharmaceutical Quality by Design offers a guide to the principles and application of Quality by Design (QbD), the holistic approach to manufacturing that offers a complete understanding of the manufacturing processes involved, in order to yield consistent and high quality products.

Leseprobe

ADVANCES IN PHARMACEUTICAL TECHNOLOGY

A Wiley Book Series

Series Editors:Dennis Douroumis, University of Greenwich, UKAlfred Fahr, Friedrich–Schiller University of Jena, GermanyJürgen Siepmann, University of Lille, FranceMartin Snowden, University of Greenwich, UKVladimir Torchilin, Northeastern University, USA

Titles in the Series

Hot‐Melt Extrusion: Pharmaceutical ApplicationsEdited by Dionysios Douroumis

Drug Delivery Strategies for Poorly Water‐Soluble DrugsEdited by Dionysios Douroumis and Alfred Fahr

Computational Pharmaceutics: Application of Molecular Modeling in Drug DeliveryEdited by Defang Ouyang and Sean C. Smith

Pulmonary Drug Delivery: Advances and ChallengesEdited by Ali Nokhodchi and Gary P. Martin

Novel Delivery Systems for Transdermal and Intradermal Drug DeliveryEdited by Ryan Donnelly and Raj Singh

Drug Delivery Systems for Tuberculosis Prevention and TreatmentEdited by Anthony J. Hickey

Continuous Manufacturing of PharmaceuticalsEdited by Peter Kleinebudde, Johannes Khinast, and Jukka Rantanen

Pharmaceutical Quality by Design: A Practical ApproachEdited by Walkiria S. Schlindwein and Mark Gibson

Forthcoming Titles:

In Vitro Drug Release Testing of Special Dosage FormsEdited by Nikoletta Fotaki and Sandra Klein

Characterization of Micro‐ and NanosystemsEdited by Leena Peltonen

Therapeutic Dressings and Wound Healing ApplicationsEdited by Joshua Boateng

Process Analytics for PharmaceuticalsEdited by Thomas de Beer, Jukka Rantanen and Clare Strachan

Pharmaceutical Quality by Design

A Practical Approach

Edited by

WALKIRIA S. SCHLINDWEIN

De Montfort UniversityLeicesterUnited Kingdom

MARK GIBSON

A M PharmaServices LtdUnited Kingdom

This edition first published 2018© 2018 John Wiley & Sons Ltd

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The right of Walkiria S. Schlindwein and Mark Gibson to be identified as the authors of the editorial material in this work has been asserted in accordance with law.

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Library of Congress Cataloging‐in‐Publication Data

Names: Schlindwein, Walkiria S., 1961– editor. | Gibson, Mark, 1957– editor.Title: Pharmaceutical quality by design : a practical approach / edited by Dr. Walkiria S. Schlindwein, Mark Gibson.Description: First edition. | Hoboken, NJ : John Wiley & Sons, 2018. | Series: Advances in pharmaceutical technology | Includes bibliographical references and index. |Identifiers: LCCN 2017030338 (print) | LCCN 2017043153 (ebook) | ISBN 9781118895221 (pdf) | ISBN 9781118895214 (epub) | ISBN 9781118895207 (cloth)Subjects: LCSH: Drugs–Design. | Drugs–Quality control.Classification: LCC RS420 (ebook) | LCC RS420 .P47 2018 (print) | DDC 615.1/9–dc23LC record available at https://lccn.loc.gov/2017030338

Cover design by WileyCover image: (Background) © ShutterWorx/Gettyimages; (Graph) Courtesy of Walkiria S. Schlindwein and Mark Gibson

List of Contributors

Noel Baker, AstraZeneca, Macclesfield, United Kingdom

Claire Beckett, Associated with OSIsoft, London, United Kingdom

Andreas Berghaus, ColVisTec AG, Berlin, Germany

Paul A. Butterworth, AstraZeneca, Macclesfield, United Kingdom

Brian Carlin, De Montfort University (visiting Professor) Lawrenceville New Jersey, United Kingdom

Alan Carmody, Pfizer, Canterbury, United Kingdom

Ian Cox, JMP Division, SAS Institute, Manchester, United Kingdom

Bruce Davis, Bruce Davis Ltd, Haslemere, United Kingdom

Joe de Sousa, AstraZeneca, Macclesfield, United Kingdom

Lennart Eriksson, Formerly associated with MKS and now associated with Sartorius Stedim Data Analytics AB, Sweden

Mark Gibson, Formerly associated with AstraZeneca and now associated with AM PharmaServices Ltd, Congleton, United Kingdom

David Holt, AstraZeneca, Macclesfield, United Kingdom

Erik Johansson, Formerly associated with MKS and now associated with Sartorius Stedim Data Analytics AB, Sweden

Line Lundsberg‐Nielsen, Lundsberg Consulting Ltd and NNE, London, United Kingdom

Martin Owen, Formerly associated with GSK and now associated with Insight by Design Consultancy Ltd, Stevenage, United Kingdom

Walkiria S. Schlindwein, De Montfort University, Leicester, United Kingdom

Siegfried Schmitt, PAREXEL Consulting, PAREXEL International, London, United Kingdom

Gerry Steele, PharmaCryst Consulting Ltd, Loughborough, United Kingdom

Conny Wikström, Formerly associated with MKS and now associated with Sartorius Stedim Data Analytics AB, Sweden

Roger Weaver, Formerly associated with Pfizer and now associated with Weaver Pharma Consulting, Canterbury, United Kingdom

Mustafa A. Zaman, PAREXEL Consulting, PAREXEL International, London, United Kingdom

Advances in Pharmaceutical Technology: Series Preface

The series Advances in Pharmaceutical Technology covers the principles, methods and technologies that the pharmaceutical industry uses to turn a candidate molecule or new chemical entity into a final drug form and hence a new medicine. The series will explore means of optimizing the therapeutic performance of a drug molecule by designing and manufacturing the best and most innovative of new formulations. The processes associated with the testing of new drugs, the key steps involved in the clinical trials process and the most recent approaches utilized in the manufacture of new medicinal products will all be reported. The focus of the series will very much be on new and emerging technologies and the latest methods used in the drug development process.

The topics covered by the series include the following:

Formulation

: The manufacture of tablets in all forms (caplets, dispersible, fast‐melting) will be described, as will capsules, suppositories, solutions, suspensions and emulsions, aerosols and sprays, injections, powders, ointments and creams, sustained release and the latest transdermal products. The developments in engineering associated with fluid, powder and solids handling, solubility enhancement, colloidal systems including the stability of emulsions and suspensions will also be reported within the series. The influence of formulation design on the bioavailability of a drug will be discussed, and the importance of formulation with respect to the development of an optimal final new medicinal product will be clearly illustrated.

Drug Delivery

: The use of various excipients and their role in drug delivery will be reviewed. Among the topics to be reported and discussed will be a critical appraisal of the current range of modified‐release dosage forms currently in use and also those under development. The design and mechanism(s) of controlled release systems including macromolecular drug delivery, microparticulate controlled drug delivery, the delivery of biopharmaceuticals, delivery vehicles created for gastrointestinal tract targeted delivery, transdermal delivery and systems designed specifically for drug delivery to the lung will all be reviewed and critically appraised. Further site‐specific systems used for the delivery of drugs across the blood–brain barrier including dendrimers, hydrogels and new innovative biomaterials will be reported.

Manufacturing

: The key elements of the manufacturing steps involved in the production of new medicines will be explored in this series. The importance of crystallization; batch and continuous processing, seeding; and mixing including a description of the key engineering principles relevant to the manufacture of new medicines will all be reviewed and reported. The fundamental processes of quality control including good laboratory practice, good manufacturing practice, Quality by Design, the Deming Cycle, regulatory requirements and the design of appropriate robust statistical sampling procedures for the control of raw materials will all be an integral part of this book series.

An evaluation of the current analytical methods used to determine drug stability, the quantitative identification of impurities, contaminants and adulterants in pharmaceutical materials will be described as will the production of therapeutic bio‐macromolecules, bacteria, viruses, yeasts, moulds, prions and toxins through chemical synthesis and emerging synthetic/molecular biology techniques. The importance of packaging including the compatibility of materials in contact with drug products and their barrier properties will also be explored.

Advances in Pharmaceutical Technology

is intended as a comprehensive one‐stop shop for those interested in the development and manufacture of new medicines. The series will appeal to those working in the pharmaceutical and related industries, both large and small, and will also be valuable to those who are studying and learning about the drug development process and the translation of those drugs into new life‐saving and life‐enriching medicines.

Dennis Douroumis

Alfred Fahr

Jürgen Siepmann

Martin Snowden

Vladimir Torchilin

Preface

The Quality by Design (QbD) concept is not a new one, but it is only in recent years that it has been adopted by the pharmaceutical industry as a systematic approach to the development and control of drug products and their associated manufacturing processes. It became, and still is, a ‘hot topic’ after the US Food and Drug Administration (FDA) observed diminished drug approval rates, and recognized that something needed to be done to address the numerous quality manufacturing issues occurring post approval due to poorly developed products and manufacturing processes. As a result, the FDA outlined its initiative to address these concerns in its report ‘Pharmaceutical Quality for the 21st Century: A Risk‐Based Approach’, and subsequently, in collaboration with major pharmaceutical companies, established a series of pharmaceutical QbD guidance documents adopted by ICH (International Conference on Harmonization) to help streamline the drug development and regulatory filing process.

The term ‘Quality by Design’ with respect to pharmaceutical development is defined in ICH guideline Q8(R2) ‘Pharmaceutical Development’ as ‘a systematic approach to development that begins with predefined objectives, emphasizes product, process understanding and process control, based on sound science and quality risk management’ (ICH, 2009). A key principle is that quality should be built into a product with a thorough understanding of the product and the manufacturing process. This includes establishing a knowledge of the risks involved in manufacturing the product and how best to mitigate those risks. This new paradigm for pharmaceutical product development employing QbD varies a great deal from the traditional approach, which was extremely empirical; should result in better control of parameters and variables; and reduce the emphasis on end‐product testing. There are also potential opportunities to operate within a broader “design space,” post approval, without the need for additional regulatory scrutiny.

Due to the combination of regulatory pressure, the carrot of regulatory flexibility, and an acceptance by many pharmaceutical companies that QbD is an improved way of working for the development of new products, it has been adopted as the preferred way of working by many companies. However, implementation has often been found challenging because the FDA and ICH guidance documents are written at a fairly high level, and it is up to each company to interpret them. Some leading pharmaceutical companies have found a way forward and have obtained approval of QbD applications, but there are many others who still struggle to implement QbD in practice and are still feeling their way.

A new group specializing in Pharmaceutical Quality by Design was initiated in 2010 at De Montfort University, Leicester School of Pharmacy, led by Walkiria S. Schlindwein, in recognition of an opportunity to fill a perceived gap in education and learning associated with QbD. A distance learning postgraduate certificate programme was launched in 2010 and expanded into a full validated MSc programme in 2012. This programme has been specifically designed with the needs of the pharmaceutical and allied industries in mind and has been created through a unique collaboration between industry and academia. A wide range of experienced industrial and regulatory experts have been engaged in preparing and delivering pre‐recorded lectures that form the core of the programme. They represent manufacturing and development companies, excipient suppliers, process equipment suppliers, data analysis software suppliers, consultancies and regulators. In addition, DMU has developed a dedicated online platform to deliver online short courses tailored to the needs of industry.

The most significant departure in the creation of a QbD training for industry programme, however, has been the completion of a dedicated laboratory to simulate the conditions for QbD in action. Here, programmes can be designed to address the specific training needs of companies from the United Kingdom and the rest of the world, to give support to institutions of all sizes within the industry.

This book, Pharmaceutical Quality by Design: A Practical Approach, is intended to complement the DMU QbD teaching materials already available to support the MSc course and distance learning modules, and also, to be consistent in terms of interpretation of the principles, approach and their application in practice.

Pharmaceutical Quality by Design: A Practical Approach includes 12 different chapters covering a broad scope of QbD aspects that are considered important by the editors and contributors. Each of the subsequent chapters are written by “experts” in their field and provide relevant, up‐to‐ date and tailored information. Each part will stand alone, but it is the sum of these individual parts that makes Quality by Design whole and provides the compelling story that will ultimately benefit patients and give clarity of understanding in what is important when designing, manufacturing and supplying products to our customers.

The content is applicable to development scientists, manufacturing specialists and those in supporting roles, such as quality, analytical, engineering, validation and more. It is intended to be helpful, practical and wide‐ranging and for use by novices, experienced practitioners or those who want to expand their current knowledge.

Walkiria S. Schlindwein

Mark Gibson

1Introduction to Quality by Design (QbD)

Bruce Davis1 and Walkiria S. Schlindwein2

1Bruce Davis Ltd, United Kingdom

2De Montfort University, Leicester, United Kingdom

1.1 Introduction

The aim of this chapter is to introduce the principles of Quality by Design (QbD) to those who want to understand pharmaceutical QbD, and that may include readers from industry, academia, regulators or indeed anyone interested in finding out more about this important subject.

The content is applicable to development scientists, manufacturing specialists and those in supporting roles, such as quality, analytical, engineering, validation and more. It is intended to be helpful, practical and wide‐ranging and for use by novices, experienced practitioners or those who want to expand their current knowledge.

Each of the subsequent chapters is written by experts in their field and provide relevant, up‐to‐date and tailored information. Each part will stand alone, but it is the sum of these individual parts that makes QbD whole and provides the compelling story that will ultimately benefit patients and give clarity of understanding in what is important when designing, manufacturing and supplying products to our customers.

So, who are these customers? Some may be our family or friends or colleagues, but most will be individuals we do not know and will never meet. A customer may choose a generic medicine from a shelf in the pharmacy, their choice perhaps being influenced by the descriptions on the packaging or by marketing and advertising, or, alternatively, they may have their medicine prescribed and administered by healthcare professionals. Some may be supporting others, for example, a parent helping their child, or an adult helping an elderly relative or colleague.

But no matter what the circumstances are in which someone takes a medicine, there is one overriding principle: that every patient, healthcare professional, parent or career has to trust the pharmaceutical industry to provide what is intended and that the medicine will be safe, efficacious and of the required quality.

So it is important that we value this trust we have been given. History says that most of the time the pharmaceutical industries have delivered on this trust, but there have been occasions when the industries have not, and such mistakes, albeit small in number compared with all the medicines that are taken, have sadly damaged the trust that customers put in the industry.

So how does this impact the development, manufacturing and distribution of pharmaceuticals? First, we should recognise that we in industry have the detailed technical knowledge, and the customers usually do not. Second, we should ensure strong linkages across the product lifecycle, from development to manufacturing to supply. Third, we not only have to understand the underlying science, what risks there might be and mitigate these risks proactively before products reach the patient, but we have to communicate these risks effectively. So, for example, if there are a million tablets in a batch, we have to be sure, to the best of our ability, that these tablets have been produced of the appropriate quality, as each one may go to a different customer.

And this is where the term QbD comes in – sometimes referred to as ‘a science and risk‐based approach’, and this set of words gives a little more insight into what QbD is about.

The definition of QbD [1] is:

A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.

The term ‘Quality by Design’ was first used by Juran in 1985 when the first draft of his book [2], published in 1992, was available for consultation by 50 senior representatives of industry. The Juran Trilogy stated: ‘Managing for quality is done by use of the same three managerial processes: planning, control and improvement’ [3].