process analytical technology

Edited by Katherine A. Bakeev Process Analytical Technology Process Analytical Technology This page intentionally left blank Process Analytical Technology Spectroscopic Tools and Implementation Strategies for the Chemical and Pharmaceutical Industries Edited by Katherine A. Bakeev Ó 2005 by Blackwell Publishing Ltd Editorial Offices: Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Tel: +44 (0)1865 776868 Blackwell Publishing Professional, 2121 State Avenue, Ames, Iowa 50014–8300, USA Tel: +1 515 292 0140 Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia Tel: +61 (0)3 8359 1011 The right of the Author to be identified as the Author of this Work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be rep roduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. First published 2005 Library of Congress Cataloging-in-Publication Data Process analytical technology /edited by Katherine A. Bakeev. p. cm. Includes bibliographical references and index. ISBN-10: 1–4051–2103–3 (acid-free paper) ISBN-13: 978–1–4051–2103–3 (acid-free paper) 1. Chemical process control—Industrial applications. 2. Chemistry, Technical. 3. Chemistry, Analytic—Technological innovations. 4. Chemistry, Analytic—Technique. 5. Spectrum analysis. 6. Pharmaceutical chemistry. I. Bakeev, Katherine A. TP155.75.P737 2005 660 0 .2—dc22 2004065962 ISBN-10: 1–4051–2103–3 ISBN-13: 978–1–4051–2103–3 A catalogue record for this title is available from the British Library Set in 10/12pt Minion by Integra Software Services Pvt. Ltd, Pondicherry, India Printed and bound in India by Gopson Papers, Noida The publisher’s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp processed using acid-free and elementary chlorine-free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. For further information on Blackwell Publishing, visit our website: www.blackwellpublishing.com Contents Contributors xiii Preface xv List of Abbreviations xvii 1 Process Analytical Chemistry: Introduction and Historical Perspective Ernest Baughman 1 1.1 Historical perspective 2 1.2 Early instrument develo pment 4 1.3 Sampling systems 7 1.4 Examples 8 References 11 2 Implementation of Process Analytical Technologies Robert Guenard and Gert Thurau 13 2.1 Introduction to implementation of process analytical technologies (PATs) in the industrial setting 13 2.1.1 Definition of process analytics 14 2.1.2 Differences between process analyzers and laboratory analysis 14 2.1.3 General industrial drivers for process analytics 15 2.1.4 Types of applications (R&D vs. Manufacturing) 16 2.1.5 Organizationa l considerations 17 2.2 Generalized process ana lytics work process 20 2.2.1 Project identification and definition 22 2.2.2 Analytical application development 24 2.2.3 Design, specify and procure 24 2.2.4 Implementatio n in production 26 2.2.5 Routine operation 27 2.2.6 Continuous improvement 28 2.3 Differences between implementation in chemical and pharmaceutical indus tries 29 2.3.1 Introduction 29 2.3.2 Business model 29 2.3.3 Technical differences 30 2.3.4 Regulatory differences 32 2.4 Conclusions 37 References 37 3 Near-Infrared Spectr oscopy for Process Analytical Chemistry: Theory, Technology and Impleme ntation Michael B. Simpson 39 3.1 Introduction 39 3.2 Theory of near-infrar ed spectroscopy 44 3.2.1 Molecular vibrations 44 3.2.2 Anharmonicity of the potential well 45 3.2.3 Combination and overtone absorptions in the near-infrared 47 3.2.4 Examples of useful near-infrared absorption bands 48 3.3 Analyser technologies in the near-infrared 51 3.3.1 The scanning grating monochromator 51 3.3.2 Light sources and detectors for near-infrared analysers 55 3.3.3 The polychromator photodiode-array a nalyser 62 3.3.4 The acousto-optic tunable (AOTF) analyser 63 3.3.5 Fourier transform near-infrared analys ers 69 3.4 The sampling interface 77 3.4.1 Introduction 77 3.4.2 Further discussion of sampling issues 84 3.4.3 The use of fibre-optics 86 3.5 Conclusion 88 Bibliography 89 4 Infrared Spectroscopy for Process Analytical Applications John P. Coates 91 Abstract 91 4.1 Introduction 92 4.2 Basic IR spectroscopy 95 4.3 Instrumentation design and technology 97 4.4 Process IR instrumentation 100 4.4.1 Commercially available IR instruments 101 4.4.2 Important IR component technologies 108 4.4.3 New technologies for IR comp onents and instruments 112 4.4.4 Requirements for process infrared analyzers 114 4.4.5 Sample handling for IR process analyzers 121 4.4.6 Issues for consideration in the implementation of process IR 124 vi Contents 4.5 Applications of process IR analyzers 126 4.6 Process IR analyzers: A review 127 4.7 Trends and directions 129 References 130 5 Process Raman Spectroscopy Nancy L. Jestel 133 5.1 How Raman spectroscopy works 133 5.2 When Raman spectroscopy works well and when it does not 136 5.2.1 Advantages 136 5.2.2 Disadvantages and risks 138 5.3 What are the special design issues for process R aman instruments? 140 5.3.1 Safety 141 5.3.2 Laser wavelength selection 142 5.3.3 Laser power and stability 142 5.3.4 Sample interface/probes 143 5.3.5 Spectrometer 144 5.3.6 Communications 146 5.3.7 Maintenance 147 5.4 Where Raman spectroscopy is being used 147 5.4.1 Reaction monitoring 147 5.4.2 In-process aid or quality-monitoring tool 155 5.4.3 Product properties 161 5.4.4 Mobile or field uses 161 5.5 What is the current state of Raman spectroscopy? 161 5.5.1 Publication reluctance 162 5.5.2 Technique maturity and long-term performance 163 5.5.3 Lack of widespread knowledge and experience 163 References 163 6 UV-Vis for On-Line Analysis Lewis C. Baylor and Patrick E. O’Rourke 170 6.1 Introduction 170 6.2 Theory 171 6.2.1 Chemical concentration 171 6.2.2 Color 172 6.2.3 Film thickness 173 6.3 Instrumentation 173 6.4 Sample interface 174 6.4.1 Cuvette/vial 174 6.4.2 Flow cells 175 6.4.3 Insertion probe 176 6.4.4 Reflectance probe 177 Contents vii 6.5 A complete process analyz er 177 6.6 Applications 178 6.6.1 Gas analysis – toluene 178 6.6.2 Liquid analysis – nickel 180 6.6.3 Solid analysis – extruded plastic color 181 6.6.4 Film thickness – polymer 182 6.6.5 Dissolution testing 183 6.6.6 Liquid analysis – vessel cleaning 185 References 186 7 Near-Infrared Chemical Imaging as a Process Analytical Tool E. Neil Lewis, Joseph W. Schoppelrei, Eunah Lee, and Linda H. Kidder 187 7.1 The process analytical technology (PAT) initiative 187 7.2 The role of near-infrared chemical imaging (NIR-CI) in the pharmaceutical industry 188 7.2.1 Characterization of solid dosage forms 188 7.2.2 ‘A picture is worth a thousand words’ 189 7.3 The development of imaging spectroscopy 190 7.3.1 Spatially resolved spectroscopy – mapping 190 7.3.2 The infrared focal-plane array (FPA) 190 7.3.3 Wavelength selection 191 7.3.4 The benefits of NIR spectroscopy 191 7.3.5 NIR imaging instrumentation 192 7.4 Chemical imaging principles 194 7.4.1 The hypercube 195 7.4.2 Data analysis 196 7.4.3 Spectral correction 197 7.4.4 Spectral pre-processing 197 7.4.5 Classification 198 7.4.6 Image processing 200 7.5 PAT applications 201 7.5.1 ‘Self-calibrating’ high-throughput content uniformity measurements 201 7.5.2 High-throughp ut applications: Counterfeit screening/quality assurance 204 7.5.3 Defeating sample dilution: Finding the needle in the haystack 206 7.5.4 Advanced dosage delivery systems 209 7.6 Processing case study one: Estimating ‘abundance’ of sample components 210 7.6.1 Experimental 211 7.6.2 Spectral correction and pre-processing 211 7.6.3 Analysis 211 7.6.4 Conclusions 217 viii Contents 7.7 Processing case study two: Determining blend homoge neity through statistical analysis 217 7.7.1 Experimental 218 7.7.2 Observing visual contrast in the image 219 7.7.3 Statistical analysis of the imag e 219 7.7.4 Blend uniformity measurement 221 7.7.5 Conclusions 222 7.8 Final thoughts 223 Acknowledgements 223 References 223 8 Chemometrics in Process Analytical Chemistry Charles E. Miller 226 8.1 Introduction 226 8.1.1 What is chemometric s? 226 8.1.2 What does it do for analytical chemistry? 227 8.1.3 What about process analytical chemistry? 228 8.1.4 Some history 228 8.1.5 Some philosophy 229 8.2 The building blocks of chemometrics 230 8.2.1 Notation 230 8.2.2 A bit of statistics 231 8.2.3 Linear regression 233 8.2.4 Multiple linear regression (MLR) 236 8.2.5 Data pre-treatment 237 8.2.6 Data compression 243 8.2.7 Spatial sample representation 249 8.2.8 Experimental desig n 250 8.3 Quantitative model building 254 8.3.1 ‘Inverse’ multiple linear regression 254 8.3.2 Classical least squares (CLS) 257 8.3.3 Principal component regression (PCR) 259 8.3.4 Projection to latent struc tures (PLS) regression 262 8.3.5 Artificial neural networks (ANN) 264 8.3.6 Other quantitative model-building tools 267 8.3.7 Overfitting and model validation 267 8.3.8 Improving quantitative model performance 274 8.4 Outliers 277 8.4.1 What are they, and why should we care? 277 8.4.2 Outliers in calibration 277 8.4.3 Outliers in prediction 283 8.5 Qualitative model building 285 8.5.1 Space definition 286 8.5.2 Measures of distance in the space 287 Contents ix [...]... Historical perspective Process analytical chemistry is a field that has developed over many years Over the past decade there has been a 5% annual growth in the use of process analytical instruments, and this growth is expected to continue.1 More recently, the term process analytical technology (PAT) has been used to describe this area that is the application of analytical chemistry and process chemistry... the process development, using the instrument With that type of head start, no one could ever catch up to their process gain from using that analyzer Similarly, DuPont needed spectroscopic process measurements and played a major role in getting dual wavelength spectrometers into field locations, as well as developing on-line mass spectrometry measurements.6 6 Process Analytical Technology The process. .. classical process analytical methods for the improvement of process development and control Particularly in the pharmaceutical industry, the acronym PAT for process analytical technology is often used to describe this newer definition of PA 2.1.2 Differences between process analyzers and laboratory analysis Several attributes distinguish process analytical methods from classic laboratory analysis Most... M Brearley 11.1 Introduction 11.2 Successful process analyzer implementation 11.2.1 A process for successful process analyzer implementation 11.2.2 How NIR process analyzers contribute to business value 11.2.3 Issues to consider in setting technical requirements for a process analyzer 11.2.4 Capabilities and limitations of NIR 11.2.5 General challenges in process analyzer implementation 11.2.6 Approaches... multivariate wavelength standardization non-dispersive infrared near-infrared near-infrared chemical imaging National Institute of Standards and Technology nuclear magnetic resonance operational qualification process analytical chemistry process analytical technology lead sulfide lead selenide principal component or personal computer principal component regression photodiode array piecewise direct standardization... process changes, then the process engineer could use the output to optimize the process Real-time data from the process GC provided data that would have taken hours to get when using off-line measurements Having rapid results is a very different goal than that of the laboratory GC where the goal is the best separation or the latest technology Many times in developing the needed stability into the process. .. Chem 2002, 74, 381A–384A 2 Clevett, K.J., Process Analyzer Technology; Wiley-Interscience; New York, 1986 3 Callis, J.B.; Illman, D.L & Kowalski, B.R., Process Analytical Chemistry; Anal Chem 1987, 59, 624A–631A 4 Beebe, K.R.; Blaser, W.W.; Bredeweg, R.A.; Chauvel, J.P Jr; Harner, R.S.; LaPack, M.; Leugers, A.; Martin, D.P.; Wright, L.G & Yalvac, E.D., Process Analytical Chemistry; Anal Chem 1993, 65,... Koch, M & Veltkamp, D.J., Process Analytical Chemistry; Anal Chem 2003, 75, 2859–2876 6 Hassell, D.C & Bowman, E.M., Process Analytical Chemistry for Spectroscopists; Appl Spectrosc 1998, 52, 18A–29A 7 Maestro, J., Sampling and Engineering Considerations In Chalmers, J.M (ed.); Spectroscopy in Process Analysis; Sheffield Academic Press; Sheffield, 2000, pp 284–335 8 Sherman, R.E., Process Analyzer Sample-Conditioning... can be described as ‘analysis in the process and is closely related to the traditional role of analytical chemistry in process control The classical scope of a process analytical method is to supplement the control scheme of a chemical, pharmaceutical or agricultural manufacturing process with data from a process analyzer that directly measures chemical or physical attributes of the sample More recently... descriptive knowledge of a process The process signature that is measured permits a determination of trending in process parameters Measurements can be made to give a direct indication of reaction progress or the composition of a mixture at a given time This information about the process can be used to make changes to keep a process running within some set limits With additional process information, and . Edited by Katherine A. Bakeev Process Analytical Technology Process Analytical Technology This page intentionally left blank Process Analytical Technology Spectroscopic Tools and Implementation Strategies. National Institute of Standards and Technology NMR nuclear magnetic resonance OQ operational qualification PAC process analytical chemistry PAT process analytical technology PbS lead sulfide PbSe. Chemometrics in Process Analytical Chemistry Charles E. Miller 226 8.1 Introduction 226 8.1.1 What is chemometric s? 226 8.1.2 What does it do for analytical chemistry? 227 8.1.3 What about process analytical