Handbook of Pharmaceutical Manufacturing Formulations, Third Edition Volume Two, Uncompressed Solid Products Handbook of Pharmaceutical Manufacturing Formulations Volume Two, Uncompressed Solid Produc.
Handbook of Pharmaceutical Manufacturing Formulations Volume Two, Uncompressed Solid Products Handbook of Pharmaceutical Manufacturing Formulations, Third Edition Volume Two, Uncompressed Solid Products Sarfaraz K Niazi CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2020 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S Government works Printed on acid-free paper International Standard Book Number-13: 978-1-138-10316-0 (Hardback) This book contains information obtained from authentic and highly regarded sources Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint Except as permitted under U.S Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com To the memory of Frederick P Siegel Professor Frederick P Siegel passed away in 2013; my teacher and later a colleague, Fred was a worldclass teacher with multiple golden apple awards He left an indelible mark on my mind how to think like a student when teaching, a piece of advice that changed my perspective on how minds interact Contents Preface to the Series—Third Edition xxv Preface to the Series—Second Edition xxvii Preface to the Series—First Edition xxxi Preface to the Volume—First Edition xxxiii Author xxxv Part I Regulatory and Manufacturing Guidelines Chapter U.S FDA Good Manufacturing Practices I Introduction II U.S FDA cGMP guidelines A. General Provisions Part 210—cGMP in Manufacturing, Processing, Packaging, or Holding of Drugs; General Part 211—cGMP for Finished Pharmaceuticals III Amendments to Part 211 23 IV U.S FDA cGMP Overview Checklist 25 V Drug Master Files and Certifications 29 A. Types of DMFs 29 Glossary 29 Chapter Guideline on the Common Technical Document for the Registration of Pharmaceuticals for Human Use 33 Background 33 Scope of the Guideline 33 General Principles 33 Organization of the Common Technical Document 33 Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use 34 Granularity of Document 34 Definition of a Document 34 Document Pagination and Segregation 37 Section Numbering Within Documents 37 Table of Contents Formatting 37 Module 2��������������������������������������������������������������������������������������������������������������������������������������� 37 Module 3��������������������������������������������������������������������������������������������������������������������������������������� 37 Module 4��������������������������������������������������������������������������������������������������������������������������������������� 37 Module 5��������������������������������������������������������������������������������������������������������������������������������������� 38 2.3 Quality Overall Summary 38 Introduction 38 2.3.S Drug Substance (Name, Manufacturer) 38 2.3.S.1 General Information (Name, Manufacturer) 38 2.3.S.2 Manufacture (Name, Manufacturer) 38 2.3.S.3 Characterization (Name, Manufacturer) 38 2.3.S.4 Control of Drug Substance (Name, Manufacturer) 39 2.3.S.5 Reference Standards or Materials (Name, Manufacturer) 39 2.3.S.6 Container Closure System (Name, Manufacturer) 39 2.3.S.7 Stability (Name, Manufacturer) 39 2.3.P Drug Product (Name, Dosage Form) 39 2.3.P.1 Description and Composition of the Drug Product (Name, Dosage Form) 39 2.3.P.2 Pharmaceutical Development (Name, Dosage Form) 39 2.3.P.3 Manufacture (Name, Dosage Form) 39 2.3.P.4 Control of Excipients (Name, Dosage Form) 39 vii viii Contents 2.3.P.5 Control of Drug Product (Name, Dosage Form) 39 2.3.P.6 Reference Standards or Materials (Name, Dosage Form) 39 2.3.P.7 Container Closure System (Name, Dosage Form) 40 2.3.P.8 Stability (Name, Dosage Form) 40 2.3.A Appendices 40 2.3.A.1 Facilities and Equipment (Name, Manufacturer) 40 2.3.A.2 Adventitious Agents Safety Evaluation (Name, Dosage Form, Manufacturer) 40 2.3.R Regional Information 40 2.4 Nonclinical Overview 40 General Aspects 40 Content and Structural Format 40 2.5 Clinical Overview 41 2.5.1 Product Development Rationale 42 2.5.2 Overview of Biopharmaceuticals 42 2.5.3 Overview of Clinical Pharmacology 42 2.5.4 Overview of Efficacy 42 2.5.5 Overview of Safety 43 2.5.6 Benefits and Risks Conclusions 44 2.5.7 Literature References 44 2.6 Nonclinical Written and Tabulated Summaries 44 Nonclinical Written Summaries 44 Introduction����������������������������������������������������������������������������������������������������������������������������������� 44 General Presentation Issues����������������������������������������������������������������������������������������������������������� 45 Use of Tables and Figures������������������������������������������������������������������������������������������������������������� 45 Length of Nonclinical Written Summaries����������������������������������������������������������������������������������� 45 Sequence of Written Summaries and Tabulated Summaries��������������������������������������������������������� 45 Content of Nonclinical Written and Tabulated Summaries 45 2.6.1 Introduction 45 2.6.2 Pharmacology Written Summary 45 2.6.2.1 Brief Summary 45 2.6.2.2 Primary Pharmacodynamics 46 2.6.2.3 Secondary Pharmacodynamics 46 2.6.2.4 Safety Pharmacology 46 2.6.2.5 Pharmacodynamic Drug Interactions 46 2.6.2.6 Discussion and Conclusions 46 2.6.2.7 Tables and Figures 46 2.6.3 Pharmacology Tabulated Summary 46 2.6.4 Pharmacokinetics Written Summary 46 2.6.4.1 Brief Summary 46 2.6.4.2 Methods of Analysis 46 2.6.4.3 Absorption 46 2.6.4.4 Distribution 46 2.6.4.5 Metabolism (Interspecies Comparison) 46 2.6.4.6 Excretion 46 2.6.4.7 Pharmacokinetic Drug Interactions 46 2.6.4.8 Other Pharmacokinetic Studies 47 2.6.4.9 Discussion and Conclusions 47 2.6.4.10 Tables and Figures 47 2.6.5 Pharmacokinetics Tabulated Summary 47 2.6.6 Toxicology Written Summary 47 2.6.6.1 Brief Summary 47 2.6.6.2 Single-Dose Toxicity 47 2.6.6.3 Repeat-Dose Toxicity (Including Supportive Toxicokinetics Evaluation) 47 2.6.6.4 Genotoxicity 47 2.6.6.5 Carcinogenicity (Including Supportive Toxicokinetics Evaluations) 47 2.6.6.6 Reproductive and Developmental Toxicity (Including Range-Finding Studies and Supportive Toxicokinetics Evaluations) 47 2.6.6.7 Local Tolerance 48 Contents ix 2.6.6.8 Other Toxicity Studies (If Available) 48 2.6.6.9 Discussion and Conclusions 48 2.6.6.10 Tables and Figures 48 2.6.7 Toxicology Tabulated Summary (See Appendix B) 48 2.7 Clinical Summary 49 2.7.1 Summary of Biopharmaceutical Studies and Associated Analytical Methods 49 2.7.1.1 Background and Overview 49 2.7.1.2 Summary of Results of Individual Studies 49 2.7.1.3 Comparison and Analyses of Results Across Studies 49 2.7.1.4 Appendix 50 2.7.2 Summary of Clinical Pharmacology Studies 50 2.7.2.1 Background and Overview 50 2.7.2.2 Summary of Results of Individual Studies 50 2.7.2.3 Comparison and Analyses of Results Across Studies 50 2.7.2.4 Special Studies 51 2.7.2.5 Appendix 51 2.7.3 Summary of Clinical Efficacy 52 2.7.3.1 Background and Overview of Clinical Efficacy 52 2.7.3.2 Summary of Results of Individual Studies 52 2.7.3.3 Comparison and Analyses of Results across Studies 52 2.7.3.4 Analysis of Clinical Information Relevant to Dosing Recommendations 53 2.7.3.5 Persistence of Efficacy and/or Tolerance Effects 54 2.7.3.6 Appendix 54 2.7.4 Summary of Clinical Safety 54 2.7.4.1 Exposure to the Drug 54 2.7.4.2 Adverse Events 55 2.7.4.3 Clinical Laboratory Evaluations 58 2.7.4.4 Vital Signs, Physical Findings, and Other Observations Related to Safety 58 2.7.4.5 Safety in Special Groups and Situations 58 2.7.4.6 Postmarketing Data 59 2.7.4.7 Appendix 59 2.7.5 Literature References 59 2.7.6 Synopses of Individual Studies 59 Module 3: Quality 60 Scope of the Guideline 60 3.1 Table of Contents of Module 60 3.2 Body of Data 60 3.2.S Drug Substance (Name, Manufacturer) 60 3.2.S.1 General Information (Name, Manufacturer) 60 3.2.S.1.1 Nomenclature (Name, Manufacturer) 60 3.2.S.1.2 Structure (Name, Manufacturer) 60 3.2.S.1.3 General Properties (Name, Manufacturer) 60 3.2.S.2 Manufacture (Name, Manufacturer) 60 3.2.S.2.1 Manufacturer(s) (Name, Manufacturer) 60 3.2.S.2.2 Description of Manufacturing Process and Process Controls (Name, Manufacturer) 60 3.2.S.2.3 Control of Materials (Name, Manufacturer) 61 3.2.S.2.4 Controls of Critical Steps and Intermediates (Name, Manufacturer) 61 3.2.S.2.5 Process Validation and/or Evaluation (Name, Manufacturer) 62 3.2.S.2.6 Manufacturing Process Development (Name, Manufacturer) 62 3.2.S.3 Characterization (Name, Manufacturer) 62 3.2.S.3.1 Elucidation of Structure and Other Characteristics (Name, Manufacturer) 62 3.2.S.3.2 Impurities (Name, Manufacturer) 62 3.2.S.4 Control of Drug Substance (Name, Manufacturer) 62 3.2.S.4.1 Specification (Name, Manufacturer) 62 3.2.S.4.2 Analytical Procedures (Name, Manufacturer) 62 3.2.S.4.3 Validation of Analytical Procedures (Name, Manufacturer) 62 3.2.S.4.4 Batch Analyses (Name, Manufacturer) 63 3.2.S.4.5 Justification of Specification (Name, Manufacturer) 63 .. .Handbook of Pharmaceutical Manufacturing Formulations Volume Two, Uncompressed Solid Products Handbook of Pharmaceutical Manufacturing Formulations, Third? ?Edition Volume Two, Uncompressed Solid. .. 42 2.5.2 Overview of Biopharmaceuticals 42 2.5.3 Overview of Clinical Pharmacology 42 2.5.4 Overview of Efficacy 42 2.5.5 Overview of Safety ... Synopses of Individual Studies 59 Module 3: Quality 60 Scope of the Guideline 60 3.1 Table of Contents of Module 60 3.2 Body of Data