Book Review on A TEXTBOOK OF PHARMACEUTICAL QUALITY ASSURANCE [As per syllabus of Pharmacy council of India (PCI)] By Dr. Harshal Ashok Pawar

About Author:

Harshal Ashok Pawar, M. Pharm., PhD (Pharmacy), MD (AM)

He is currently working as an Assistant Professor with Dr. L. H. Hiranandani College of Pharmacy, Ulhasnagar, (Affiliated to University of Mumbai, India). He has 15 years of teaching and industry research experience. He also worked as a Head of Department of Quality Assurance for six years. He worked with various pharmaceutical industries like Medley, Charak and Alkem Research Centre, Mumbai. He has published more than 60 research and review articles in various national / international journals of repute. He has also presented various research papers in national / international conference, seminars, symposia and workshops. He has two Indian and two international patents to his credit. He has received research grants from University of Mumbai. He is on editorial board and reviewer of various National / International journals. He has guided 25 M. Pharmacy Research scholars in the subject of Quality Assurance. He is also recognized PhD guide of University of Mumbai. He has authored seven books in the field of Pharmaceutical sciences. He is a life member of Association of Pharmaceutical Teachers of India (APTI).

About Book:

A Textbook of Pharmaceutical Quality Assurance is an outcome of sincere efforts made by author to collect, compile and simplify various aspects of Quality assurance keeping in view the level and learning objectives of Pharmacy students at undergraduate level. This book is prepared according to new syllabus of B. Pharmacy, introduced by Pharmacy Council of India (PCI). The present efforts will help the students to understand the subject matter easily.

 This book mainly covers the syllabus in the subject of Pharmaceutical Quality Assurance at the undergraduate level, implemented in most of the Indian and Foreign Universities. The book provides an overview about quality assurance, Good Manufacturing Practice (GMP), validation, Good Laboratory Practices (GLP) and documentation practice followed in industry. It is the most comprehensive book which deals with the important aspects of Quality assurance like cGMP, Quality control tests on packaging material, Pharmaceutical documentation, Quality certifications and Regulatory affairs. The principles of GMP and GLP are discussed which are expected to guide the manufacturer and the regulator for maintaining high scientific and professional standards for ensuring only drugs and pharmaceuticals of highest quality are produced and marketed.

The present book is divided in to five units.  The unique feature of this book is the presentation of fundamental concepts in a simple, lucid and self-explanatory form. Each unit includes learning objectives, general introduction to the topics covered, discussion on various regulatory aspects considering current regulatory guidelines and Pharmacopoeial requirements. At the end of each unit a list of probable questions to be asked in semester examination is provided so as to help the student to evaluate themselves. Every effort is taken to provide most authenticated and precise information and views, but readers are advised to refer the latest guidelines and cited references for more details.

BOOK CONTENTS

1.  QUALITY ASSURANCE AND QUALITY MANAGEMENT CONCEPTS…… 1

1.  Introduction……………………………………………………………………………………….. 1

• 1. Definition of Quality……………………………………………………………………… 2

1.2 Quality of a Pharmaceutical Product……………………………………………… 2

2.  Concept Of Quality Assurance………………………………………………………….. 3

• 1 Objectives of Quality Assurance…………………………………………………….. 4
• 2 Requirements of Quality Assurance System as per WHO……………… 4
• 3 Quality Assurance Methods…………………………………………………………… 5

3. Good Manufacturing Practices (GMP) For Pharmaceutical Products…… 6

• 1 What is Good Manufacturing Practice (GMP)?………………………………. 6
• 2 What GMP covers?…………………………………………………………………………. 7

4.  Quality Control…………………………………………………………………. 8

• 1 Objectives of Quality Control…………………………………………………………. 8
• 2 Basic Requirements of Quality Control………………………………………….. 9
• 3 Tools /Methods /Techniques of Quality Control…………………………. 10

5.  Comparison Of Quality Assurance and Quality Control………………. 10

2.  TOTAL QUALITY MANAGEMENT (TQM)……………………………………………. 12

1.  Introduction…………………………………………………………………………………….. 12

2.  Quality Management Philosophies………………………………………. 14

3.  Definitions Of TQM…………………………………………………………………………. 17

4.  Benefits Of TQM………………………………………………………………………………. 17

5.  Disadvantages / Limitations of TQM…………………………………… 18

6.  Characteristics Of TQM…………………………………………………………………… 18

7.  Total Quality Management Principles…………………………………………… 18

8.  Elements Of TQM…………………………………………………………….. 18

9.  TQM In Pharmaceutical Industry…………………………………………………… 22

9.1 Application of TQM in Pharmaceutical Industry………………………….. 23

10.  Reasons of Failures in Implementation of TQM Approach…………. 25

3.  ICH GUIDELINES……………………………………………………………….. 28

1.  Introduction…………………………………………………………………………………….. 28

• 1 Mission of ICH……………………………………………………………………………… 29
• 2 The Need to Harmonise………………………………………………………………… 30
• 3 Process of Harmonization…………………………………………………………….. 31

2.  Organization of ICH…………………………………………………………. 33

3.  Classification of ICH Guidelines…………………………………………………….. 35

4.  Stability Testing Guidelines (Q1A – Q1F)*…………………………………….. 38

• 1. Stability Testing Guidelines for New Drug Substance………………… 41
• 2. New Drug Product………………………………………………………………………. 47

4.3 Photostability Testing (Q1B Guidelines)………………………………………. 56

4.  QUALITY BY DESIGN (QBD)………………………………………………………………. 59

1.  Introduction…………………………………………………………………………………….. 59

• 1 QbD in Pharmaceutical Development…………………………………………. 61
• 2 Definitions of Quality by Design………………………………………………….. 63
• 3 Objectives of Pharmaceutical QbD………………………………………………. 63
  • 4 Comparison of Traditional and QbD Approach of Pharmaceutical
  • Development……………………………………………………………………………………………………. 63
• 5 Benefits of QbD to Industry…………………………………………………………. 65
• 6 Opportunities………………………………………………………………………………. 66

2.  Important Definitions…………………………………………………………………….. 67

3.  Elements / Components of QbD…………………………………………. 68

4.  Tools of QbD…………………………………………………………………… 75

• 1 Prior Knowledge…………………………………………………………………………… 75
• 2 Risk Assessment…………………………………………………………………………. 76
• 3 Mechanistic Model, Design of Experiments, and Data Analysis……… 77
• 4 Process Analytical Technology (PAT)……………………………………………. 78

5.  Steps For Pharmaceutical Qbd Implementation………………………….. 81

5. ISO 9000 AND ISO 14000……………………………………………………. 84

1. Introduction…………………………………………………………………………………….. 85

2. History And Revisions: Iso 9000:2000, 2008, 2015……………….. 86

3. ISO 9000………………………………………………………………………… 86

• 1 Objectives of ISO 9000…………………………………………………………………. 87
• 2 Benefits of ISO 9000 (Why to adopt ISO 9000?)………………………….. 87
• 3 ISO 9000 Series standards………………………………………………………….. 88

3.4 ISO 9000:2000……………………………………………………………………………… 89

3.5 ISO 9004………………………………………………………………………………………. 89

4.  Elements Of ISO 9000 Quality Management Systems…………….. 90

5.  ISO9000 Principles Of Quality Management……………………………….. 93

6.  Advantages Of ISO 9000…………………………………………………… 94

7.  Disadvantages Of ISO 9000……………………………………………….. 96

8. ISO 14000……………………………………………………………………… 97

9.  Components Of ISO 14000 Series………………………………………. 97

10. Benefits Of ISO 14000 (Why To Adopt The ISO 14000 Standard?)….. 99

11. Registration Process – Steps To Follow……………………………………… 100

6.  NABL ACCREDITATION…………………………………………………….. 103

1.  Introduction………………………………………………………………………………….. 103

2.  Why Laboratory Accreditation?…………………………………………………… 106

2.1  Benefits of Accreditation……………………………………………………………. 106

• 2 Scope of Accreditation……………………………………………………………….. 108

3.  Preparation And Eligibility For Accreditation……………………………. 108

4.  Process Of Accreditation………………………………………………………………. 110

7.  ORGANIZATION AND PERSONNEL………………………………………. 114

1.  Introduction…………………………………………………………………………………… 114

2.  Personnel (Who Guidelines)………………………………………………………….. 116

• 1 Principle…………………………………………………………………………………….. 116
• 2 General requirements………………………………………………………………… 116

2.3  Key personnel…………………………………………………………………………….. 117

3.  Training

• 1 Types of training………………………………………………………………………… 121

3.2  Training as per WHO guidelines………………………………………………… 122

4.  Personal Hygiene (WHO guidelines)…………………………………………….. 123

5.  Personnel Records…………………………………………………………………………. 124

8.  PREMISES………………………………………………………………………. 126

1.  Introduction…………………………………………………………………………………… 126

• 1 Essentials / Elements (General Requirements of Quality Premises)……. 127

2.  Location…………………………………………………………………………………………. 127

3.  Pharmaceutical Plant Layout……………………………………………………….. 128

• 1 What is a pharmaceutical plant layout?……………………………………. 128
• 2 Features of a good pharmaceutical plant layout……………………….. 128
• 3 Advantages of a good pharmaceutical plant layout……………………. 129

4.  Design And Construction……………………………………………………………… 129

• 1 Plan and Layout…………………………………………………………………………. 130
• 2 Design, Construction, And Validation Of Pharmaceutical Facilities…. 132

4.3  Premises…………………………………………………………………………………….. 136

5.  Maintenance………………………………………………………………………………….. 141

6.  Sanitation…………………………………………………………………….. 141

• 1 Requirements as per WHO guidelines…………………………………………. 142
• 2 Sanitation for sterile pharmaceutical products………………………………. 142

7.  Utilities And Sterile Area………………………………………………… 143

• 1 Water systems……………………………………………………………………………. 143
• 2 Compressed gases and vacuum systems………………………………………. 145
• 3 Cooling systems………………………………………………………………………….. 145

8.  Aseptic Area And Parenteral Production…………………………………….. 146

• 1 Areas in parenteral processing……………………………………………………. 146
• 2 Requirements for design of aseptic area………………………………………… 148

9.  Control Of Contamination……………………………………………….. 151

• 1 Sources of Contamination and its Prevention………………………………… 152

10.  Environmental Control…………………………………………………. 154

9.  EQUIPMENT’S AND RAW MATERIALS………………………………….. 157

1.  Introduction………………………………………………………………………………….. 157

2.  Equipment’s…………………………………………………………………. 158

• 1 Types of Equipment’s………………………………………………………………… 159
• 2 Life cycle of an Equipment………………………………………………………… 159
  • 3 Management of Equipment’s in Pharmaceutical Plants as per International GMP
  •  
  • Literature………………………………………………………………………………………… 159

3.  Equipment Selection…………………………………………………………………….. 160

• 1 Factors to be considered during equipment selection………………. 160

4.  Purchasing…………………………………………………………………………………….. 162

• 1 Stores and purchase committee……………………………………………….. 162
• 2 Purchase specifications…………………………………………………………….. 163

5.  Maintenance Of Equipment’s………………………………………………………. 164

• 1 Objectives of Maintenance………………………………………………………… 164
• 2 Types of maintenance……………………………………………………………….. 164

6.  Requirements For Equipment As Per Who Guidelines…………… 165

7.  Raw Materials……………………………………………………………….. 166

• 1 Factors to be considered while purchasing the materials…………….. 167
• 2 Purchase specification………………………………………………………………. 167
• 3 General Specifications for Raw Materials (Contents of Raw

material monograph)……………………………………………………………………….. 168

• 4 Steps involved in purchase procedure………………………………………. 169
• 5 Vendor selection and Certification……………………………………………. 169

8.  Maintenance Of Stores…………………………………………………………………. 170

9.   WHO Guidelines For Raw Materials……………………………………. 171

• 1 General requirements……………………………………………………………….. 171
• 2 Starting materials……………………………………………………………………… 172
• 3 Packaging materials………………………………………………………………….. 173
• 4 Finished products……………………………………………………………………… 174

10.  QUALITY CONTROL………………………………………………………… 176

1.  Introduction………………………………………………………………………………….. 176

• 1 Definitions…………………………………………………………………………………. 177

• 2 Types of Package……………………………………………………………………….. 178
• 3 Associated Components……………………………………………………………. 179

2.  Ideal Requirements of Good Package / Container (Hazards Encountered

By Package)…………………………………………………………………………………………. 179

3.  Package Testing Procedure………………………………………………………….. 180

• 1 Testing of material…………………………………………………………………….. 180
• 2 Testing of Packages…………………………………………………………………… 181
• 3 Instrumental Techniques used for Quality control of Packaging

material………………………………………………………………………… 181

4.  Composition Of Package………………………………………………………………. 181

5.  Quality Control of Packaging Components………………………………… 182

• 1 Containers………………………………………………………………………………… 182
• 2 Plastic Containers……………………………………………………………………… 194
• 3 Metal containers……………………………………………………………………….. 198

6.  Closures………………………………………………………………………. 201

• 1 Types of closures……………………………………………………………………….. 201
• 2 Materials used for making closures………………………………………….. 201
• 3 Test for Closures……………………………………………………………………….. 202

7.  Secondary Packaging Components……………………………………………… 204

• 1 Paper, Paperboard and Cardboard……………………………………………. 205
• 2 Evaluation of Secondary Packaging Components……………………… 205

11. GOOD LABORATORY PRACTICES……………………………………… 210

1.  Introduction………………………………………………………………………………….. 211

• 1 Aims / Goals of GLP………………………………………………………………….. 211
• 2 Benefits of GLP………………………………………………………………………….. 212
• 3 Fundamentals of GLP………………………………………………………………… 213
• 4 Definition and Principles of GLP………………………………………………… 213

2.  General Provisions…………………………………………………………. 218

• 1 Scope…………………………………………………………………………………………. 218
• 2 Important Definitions……………………………………………………………….. 218
• 3 Applicability to studies performed under grants and contracts… 220
• 4 Inspection of a testing facility……………………………………………………. 220

3.  Organization And Personnel…………………………………………….. 220

• 1 Personnel…………………………………………………………………………………… 220
• 2 Testing facility management……………………………………………………… 221
• 3 Study director……………………………………………………………………………. 222
• 4 Quality assurance unit……………………………………………………………… 222

4.  Facilities………………………………………………………………………………………… 224

• 1 General………………………………………………………………………………………. 224
• 2 Animal care facilities………………………………………………………………….. 224
• 3 Animal supply facilities……………………………………………………………… 224
• 4 Facilities for handling test and control articles………………………….. 225
• 5 Laboratory operation areas………………………………………………………… 225
• 6 Specimen and data storage facilities………………………………………….. 225

5.  Equipment……………………………………………………………………. 225

• 1 Equipment design………………………………………………………………………. 225
• 2 Maintenance and calibration of equipment……………………………….. 225

6.  Testing Facilities Operation…………………………………………………………. 226

• 1 Standard operating procedures…………………………………………………. 226
• 2 Reagents and solutions……………………………………………………………… 227
• 3 Animal care………………………………………………………………………………… 227

7.  Test And Control Articles…………………………………………………………….. 228

• 1 Test and control article characterization……………………………………. 228
• 2 Test and control article handling……………………………………………….. 229
• 3 Mixtures of articles with carriers……………………………………………….. 229

8. Protocol For Conduct Of A Nonclinical Laboratory Study………….. 230

• 1 Protocol………………………………………………………………………………………. 230
• 2 Conduct of a nonclinical laboratory study…………………………………. 231

9. Records And Reports…………………………………………………………………….. 231

• 1 Reporting of nonclinical laboratory study results……………………… 231
• 2 Storage and retrieval of records and data………………………………….. 233
• 3 Retention of records…………………………………………………………………… 233

10.  Disqualification Of Testing Facilities………………………………………… 235

• 1 Purpose……………………………………………………………………………………. 235
• 2 Grounds for disqualification…………………………………………………….. 235
• 3 Notice of and opportunity for hearing on proposed disqualification…. 235
• 4 Final order on disqualification…………………………………………………. 236
• 5 Actions upon disqualification…………………………………………………… 236
• 6 Public disclosure of information regarding disqualification…….. 237
• 7 Alternative or additional actions to disqualification………………… 237
• 8 Suspension or termination of a testing facility by a sponsor…… 238
• 9 Reinstatement of a disqualified testing facility………………………… 238

12. COMPLAINT, RETURN GOODS, RECALL AND WASTE DISPOSAL…… 240

1.  Introduction…………………………………………………………………………………… 240

2.  Complaint…………………………………………………………………….. 242

• 1 Need for Complaint Handling System………………………………………… 242
• 2 Types of complaint encountered………………………………………………… 242

3.  Complaint Handling / Evaluation……………………………………… 243

• 1 Evaluation of Complaint…………………………………………………………….. 244
• 2 Standard operating procedure for handling complaint……………… 245
• 3 WHO Guidelines for Review of Complaint………………………………….. 246

4.  Handling Of Return Goods……………………………………………….. 247

• 1 Classification of returned goods………………………………………………… 248
• 2 Record of return goods………………………………………………………………. 248

5.  Product Recall / Withdrawal………………………………………………………… 248

• 1 Definitions………………………………………………………………………………….. 248
• 2 Reasons for Recall / withdrawal of Product………………………………. 249
• 3 Recall Classification…………………………………………………………………… 249
• 4 Basic information required for recall…………………………………………. 249
• 5 Stages of recall procedure……………………………………………… 250
• 6 Implementation of recall communication…………………………………… 251
• 7 Contents of recall communication……………………………………. 251
• 8 WHO guidelines for Recall…………………………………………………………. 251

6.  Waste Disposal………………………………………………………………. 252

• 1 Procedure for disposal of pharmaceutical waste………………………… 252

13. DOCUMENT MAINTENANCE IN PHARMACEUTICAL INDUSTRY….. 256

1.  Introduction………………………………………………………………………………….. 257

• 1 Purpose of Documentation………………………………………………………… 257

2.  General Requirements About Documentation (As

Per WHO Guidelines)…………………………………………………………………………. 258

3.  Batch Formula Record (BFR) / Batch Production Record (BPR)

/ Batch Processing And Control Records (BPCR) /

Batch Manufacturing Record (BMR)………………………………………………… 259

4.  Mater Formula Record (MFR) / Master Production

Instructions / Master Production And Control Records

(MPCR) / Master Formula Card (MFC)……………………………………………… 262

5.  Standard Operating Procedure (SOP) And Other Documents……. 263

6.  Quality Audit………………………………………………………………… 266

• 1 Reasons for auditing………………………………………………………………….. 267
• 2 Types of Audit…………………………………………………………………………….. 267

6.3  Procedure for conducting an audit…………………………………………….. 267

• 4 Audit preparation………………………………………………………………………. 268
• 5 Conducting of audit…………………………………………………………………… 268
• 6 Completing and follow up of audit…………………………………………….. 269

7.  Product Quality Review………………………………………………………………… 269

8.  Quality Documentation………………………………………………………………… 270

9.  Reports And Documents………………………………………………………………. 271

10.  Distribution Records…………………………………………………………………… 272

14. CALIBRATION AND VALIDATION

1.  Introduction…………………………………………………………………………………… 276

2.  Important Definitions…………………………………………………………………… 276

3.  Qualification Process……………………………………………………………………. 277

• 1 Qualification stages……………………………………………………………………. 278

4.  What Is Equipment Calibration?…………………………………………………. 281

• 1 Scope/ Purpose of Calibration…………………………………………………… 281
• 2 When to perform Calibration?……………………………………………………. 282
• 3 Types of Calibration…………………………………………………………………… 282

5.  Validation of Equipment…………………………………………………. 284

• 1 Need of Equipment Validation……………………………………………………. 284

6.  Validation…………………………………………………………………….. 285

• 1 Various Definitions of Validation……………………………………………….. 285
• 2 Reasons for Validation……………………………………………………………….. 285
• 3 Scope of Validation…………………………………………………………………….. 286
• 4 Types of Validation…………………………………………………………………….. 287
• 5 Validation Protocol…………………………………………………………………….. 289
• 6 Validation Master Plan (VMP) / Master Validation Plans (MVP)……. 290

7.  Calibration of PH Meter…………………………………………………… 293

• 1 Construction of pH meter…………………………………………………………… 293
• 2 Calibration Procedure………………………………………………………………… 294

8.  Qualification Of UV-Visible Spectrophotometers……………………….. 295

• 1 Installation Qualification……………………………………………………………. 296
• 2 Operational Qualification…………………………………………………………… 296
• 3 Calibration of UV-VIS spectrophotometer………………………………….. 297
• 4 Performance Qualification………………………………………………………….. 299

9.  General Principles Of Analytical Method Validation…………………. 301

• 1 Principle…………………………………………………………………………………….. 301
• 2 General requirements………………………………………………………………… 302
• 3 Analytical Method Validation…………………………………………………….. 303

15. WAREHOUSING AND MATERIALS MANAGEMENT…………………. 312

1.  Introduction…………………………………………………………………………………… 312

2.  Role / Functions of Warehousing………………………………………………… 313

3.  Types of Warehouses………………………………………………………. 314

4.  Warehouse Location……………………………………………………………………… 315

5.  Why is Good Warehouse Practices (GWP) Important?……………….. 315

6.  Good Warehouse Practices (GWP)………………………………………………… 316

• 1 Premises…………………………………………………………………………………….. 316
• 2 Security……………………………………………………………………………………… 316
• 3 Temperature and Humidity Control…………………………………………… 317
• 4 Equipment’s……………………………………………………………………………….. 317
• 5 Personnel……………………………………………………………………………………. 317
• 6 Sanitation…………………………………………………………………………………… 318
• 7 Receipt of incoming goods………………………………………………………….. 318
• 8 Assembling orders and issuing goods………………………………………… 318
• 9 Packing for transportation…………………………………………………………. 319
• 10 Transport…………………………………………………………………………………. 319
• 11 Records…………………………………………………………………………………….. 320

7. Material Management…………………………………………………………………. 321

7.1  Objectives…………………………………………………………………………………… 322

7.2  Functions of Material Management……………………………………………. 322

7.3  Purchasing…………………………………………………………………………………. 322

7.4  Stores Management……………………………………………………………………. 325

• 5 Salvaging and disposal of scrap and surplus…………………………….. 326

8.  Materials Management for API (As per US FDA – Q7A –

GMP guidance for API)………………………………………………………………………. 326

8.1  General Controls………………………………………………………………………… 326

8.2  Receipt and Quarantine…………………………………………………………….. 326

8.3  Sampling and Testing of Incoming Production Materials…………… 327

8.4  Storage……………………………………………………………………………………….. 328

• 5 Re-evaluation…………………………………………………………………………….. 328

ANNEXURES………………………………………………………………………. 330

MODEL QUESTION PAPERS…………………………………………………… 403

BIBLIOGRAPHY…………………………………………………………………… 404

KEY WORD INDEX……………………………………………………………….. 408

Publishers Note:

Everest’s New Arrival for Semester VI B.Pharm All India Colleges

A Textbook of Pharmaceutical Quality Assurance 

by

Dr. Harshal Ashok Pawar

As per PCI Syllabus Guidelines

The Book has been foreworded and recommended by Shri Jagannath Shinde who is the President, Chairman, MD of a number of Chemists, Druggists & Distributors Associations of India, member of various Regulatory Bodies of India such as PCI, Maharashtra State Pharmacy Council etc.  as well as Member of Maharashtra Legislative Council.

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