4th Edition

Handbook of Validation in Pharmaceutical Processes, Fourth Edition

    1061 Pages 230 B/W Illustrations
    by CRC Press

    Revised to reflect significant advances in pharmaceutical production and regulatory expectations, Handbook of Validation in Pharmaceutical Processes, Fourth Edition examines and blueprints every step of the validation process needed to remain compliant and competitive. This book blends the use of theoretical knowledge with recent technological advancements to achieve applied practical solutions. As the industry's leading source for validation of sterile pharmaceutical processes for more than 10 years, this greatly expanded work is a comprehensive analysis of all the fundamental elements of pharmaceutical and bio-pharmaceutical production processes. Handbook of Validation in Pharmaceutical Processes, Fourth Edition is essential for all global health care manufacturers and pharmaceutical industry professionals.

    Key Features:

    • Provides an in-depth discussion of recent advances in sterilization
    • Identifies obstacles that may be encountered at any stage of the validation program, and suggests the newest and most advanced solutions
    • Explores distinctive and specific process steps, and identifies critical process control points to reach acceptable results
    • New chapters include disposable systems, combination products, nano-technology, rapid microbial methods, contamination control in non-sterile products, liquid chemical sterilization, and medical device manufacture

    Chapter 1        Why Validation?        

    James Agalloco

    Chapter 2        Facility Design for Validation 

    Phil DeSantis

    Chapter 3        Modular Facilities – Meeting the Need for Flexibility

    Maik Jornitz and Sidney Backstrom

    Chapter 4        Commissioning and Qualification     

    Phil DeSantis and S. Ostrove

    Chapter 5        Design & Quaification of Controlled Environments  

    Franco De Vecchi and Phil DeSantis

    Chapter 6        Validation of Pharmaceutical Water Systems           

    William V. Collentro

    Chapter 7        Validation of Critical Utilities

    David W. Maynard

    Chapter 8        Calibration and Metrology    

    Goran Bringert

    Chapter 9        Risk Management and Thermal Validation   

    Goran Bringert

    Chapter 10      Change Control          

    S. Osgrove and Phil DeSantis


    John Shirtz

    Chapter 12      Biological Indicators  

    Hurt McCauley and Nicole Robichaud

    Chapter 13      Steam Sterilization in Autoclaves      

    Phil DeSantis

    Chapter 14      Validation of Terminal Sterilization   

    Kevin D. Trupp and Thomas J. Berger

    Chapter 15      Steam Sterilization-in-Place Technology and Validation       

    James Agalloco

    Chapter 16      Dry Heat Sterilization 

    George Schaeffer and Kishore Warrier

    Chapter 17      Depyrogenation by Inactivation and Removal          

    Karen Zink McCullough and Allen Burgenson

    Chapter 18      Ethylene Oxide Sterilization   

    James Agalloco

    Chapter 19      Validation of chlorine dioxide Sterilization   

    Mark A. Czarneski and Paul Lorcheim

    Chapter 20      Liquid Phase Sterilization       

    James Agalloco

    Chapter 21      Vapor Sterilization and Decontamination     

    James Agalloco

    Chapter 22      Validation of the Radiation Sterilization of Pharmaceuticals

    Geoffrey P. Jacobs

    Chapter 23      Validation of Sterilizing Grade Filters

    Suraj B. Baloda

    Chapter 24      Disinfecting Agents: The Art of Disinfection  

    Arthur Vellutato Jr

    Chapter 25      Cleaning and Disinfecting Laminar Flow Workstations, Bio Safety Cabinets and Fume Hoods           

    Arthur Vellutato Jr

    Chapter 26      Contamination Control for Component Introduction to Classified Areas    

    Arthur Vellutato Jr

    Chapter 27      Aseptic Processing for Dosage Form Manufacture   

    James Agalloco & James Akers

    Chapter 28      Validation of Manual Aseptic Processes        

    James Agalloco & James Akers

    Chapter 29      Validation of Aseptic Processing for Bulk Pharmaceutical Chemicals          

    James Agalloco and Phil DeSantis

    Chapter 30      Qualification and Validation of Advanced Aseptic Processing Technologies

    James Agalloco & James Akers

    Chapter 31      Total Particle  Monitoring     

    Mark Hallworth

    Chapter 32      Environmental Monitoring    

    Jeanne Moldenhauer

    Chapter 33      Validation of Container Component Preparation     

    William G. Lindboe

    Chapter 34      Validation of Lyophilization   

    Joseph P. Brower

    Chapter 35      Validation of Packaging Processes for Sterile Products         

    Charles Levine 

    Chapter 36      Validation of Active  Pharmaceutical Ingredients     

    James Agalloco & Phil DeSantis

    Chapter 37      Cell Culture  Process Validation including Cell Bank Qualification   

    Anne B. Tolstrup, Steven I. Max, Denis Drapeau and Timothy S. Charlebois

    Chapter 38      Validation of Recovery and Purification Processes   

    Frank Riske and Howard L. Levine

    Chapter 39      Validation of Process Chromatography         

    Günter Jagschies

    Chapter 40      Single Use Technologies and Systems           

    A. Mark Trotter and Derek Pendlebury

    Chapter 41      Considerations for Process Validation for Cell  and Gene Therapies

    Karen Zink McCullough, Anthony Thatcher and Merrick Endejann

    Chapter 42      Validation of Solid Dosage Forms      

    William G. Lindboe

    Chapter 43      Validation of Validation of Oral / Topical Liquids & Semi-Solids       

    William G. Lindboe

    Chapter 44      Validation of Non-Sterile Packaging Operations       

    William G. Lindboe

    Chapter 45      Validation of Cleaning Processes

    Rebecca Brewer

    Chapter 46      Validation of Training

    Chris Smalley

    Chapter 47      Vendor Qualification and Validation

    Maik Jornitz

    Chapter 48      Validation of Clinical Trial Manufacturing    

    Warren Charlton and Tom Ingallinera

    Chapter 49      Validation of New Products   

    Norman Elder

    Chapter 50      Retrospective / Continuous Process Validation        

    Kevin M Jenkins

    Chapter 51      Validation & 6 Sigma 

    Robert Bottome

    Chapter 52      Validation and Contract Manufacturing        

    Michael C. Beckloff

    Chapter 53      Computerized Systems Validation     

    Saeed Tafreshi

    Chapter 54      Risk Based Validation of Laboratory Information Management Systems     

    RD McDowall and Jeff Eshelman

    Chapter 55      Control Systems Validation   

    Phil DeSantis and Steven Osgrove

    Chapter 56      Process Analytical Technology and Validation          

    Ajaz Hussein

    Chapter 57      Validation of Analytical Procedures and Physical Methods  

    Francis E. Beideman

    Chapter 58      Validation of Microbial Methods       

    Anthony Grilli

    Chapter 59      "Rapid Methods for Aseptic Processing and Their Validation" 

    Jeanne Moldenhauer

    Chapter 60      Extractables and Leachables in Drug Products: An Overview           

    Will Parker and Don DeCou

    Chapter 61      Evolution and Implementation of Validation in the United States   

    James Agalloco and Phil DeSantis

    Chapter 62      Validation in Europe - What are the Differences?    

    Trevor Deeks

    Chapter 63      Japanese Approach to Validation      

    Satoshi Sugimoto, Mitsuo Mori, Kiyoshi Mochizuki, Keisuke Nishikawa, Takuji Ikeda, Yusuke Matsuda, Hiroaki Nakamura

    Chapter 64      Organization of Validation in a MultiNational Pharmaceutical Company    

    Kevin M Jenkins

    Chapter 65      Validation in a Small Pharmaceutical Company        

    Stephen C. Tarallo

    Chapter 66      Regulatory Aspects of Process Validation in the United States        

    James Agalloco and Robert Mello

    Chapter 67      The Future of Validation        

    James Agalloco and Phil DeSantis


    James Agalloco is President of Agalloco & Associates, a technical service firm to the pharmaceutical and biotechnology industry. He was previously Director, Worldwide Validation and Automated Technology for Bristol-Myers Squibb. He received his BS in Chemical Engineering from Pratt Institute in 1968 and his MS, also in Chemical Engineering from Polytechnic Institute of New York in 1979. He received his MBA in Pharmaceutical Studies from Fairleigh Dickinson University in 1983. He is a past President of the Parenteral Drug Association and served as an Officer or Director from 1982 to 1993. He is a member of USP’s Microbiology and Sterility Assurance Expert Committee for 2005-2015. He is a frequent author and lecturer on sterilization, aseptic processing and process validation.

    This revised and updated fourth edition provides a comprehensive overview of
    validation methodologies applicable in the manufacturing process of various
    pharmaceuticals. This reference may be viewed as a guide to developing rational
    control processes to ensure the quality of pharmaceutical products. This
    edition includes new topics related to biologics and single-use technologies.

    This book aims to offer a comprehensive guide to developing and controlling
    pharmaceutical manufacturing processes to ensure the safety and quality of the
    products. For the past several years, the FDA has been promoting the concept of
    Quality by Design (QBD) to manufacture safe and effective drug products.
    Validation refers to the essential controls or evidence-based documented
    processes that consistently provide a high degree of quality assurance of
    manufacturing quality products. This reference provides a theoretical and
    practical basis for consistently establishing processes to produce products
    with predetermined specifications. Therefore, the objectives of this book are
    valuable to pharmaceutical industry professionals.

    According to the authors, this reference would be helpful to all "industry
    professionals." This reference is a valuable guide to individuals concerned
    about the process validation in pharmaceutical manufacturing. Similar to the
    previous editions, this fourth edition is expected to be well utilized by the
    professionals working in process validation. The authors are reputable industry
    professionals. The contributors are primarily from the industry with relevant

    This book should be considered as a reference guide to pharmaceutical process
    validation. In 67 chapters, this reference presents content related to the
    conceptual framework and the practical aspects of developing and controlling
    pharmaceutical processes to ensure product quality. The fundamental aspects of
    pharmaceutical process validation have been expanded from the previous edition.
    A few new chapters have been added. The new topics include gene therapy and
    single-use technologies. The new chapters on process validation of combination
    products, nanotechnology, disposable system, and medical device manufacturing
    are expected to be informative and valuable to industry professionals. The
    authors' years of industry experience have helped them discuss the challenges
    and opportunities in various stages of a validation program. The authors'
    insight into the solutions for possible challenges in process validation is
    expected to be helpful to the target audience. The chapter on process
    validation for cell and gene therapies succinctly provides insight into the
    complexity of and current trends in process validation of biotechnology-based
    products. The interested audience will well utilize the information to make
    strategic decisions about the validation of bioprocessing. The reference
    provides discussions on Six Sigma approaches toward process validation. In
    addition, discussions on Process Analytical Technology and Validation and
    Computerized Systems Validation are practical from the industry perspective.
    The authors have shared their perspectives on the future of validation in a
    short chapter, which readers are expected to find interesting. There are three
    chapters on approaches to validation in the United States, Europe, and Japan.
    People working in multinational pharmaceutical companies should find those
    chapters handy. The authors have provided sufficient flow charts and diagrams
    to facilitate understanding. The reference has become voluminous to include
    relevant topics. Therefore, it could be developed in two or three volumes. Some
    of the image quality could be improved.

    This reference provides theoretical and practical considerations in identifying
    critical process control issues related to the manufacturing of
    pharmaceuticals. This fourth edition has a few new topics related to emerging
    trends in pharmaceutical preparations. Pharmaceutical scientists,
    manufacturers, engineers, drug quality assurance and regulatory personnel,
    project and program managers, and information system professionals are expected
    to benefit from this reference. A few books are available related to this
    subject matter, but they are not as comprehensive as this one. This book will
    serve its purpose as a reference guide. New chapters have enriched this fourth

    - Rahmat M. Talukder, PhD, RPh (The University of Texas at Tyler)