Sanjay Garg, PhD, is an associate professor at the School of Pharmacy, University of Auckland, Auckland, New Zealand, and a member of the Pharmaceutical Technology Editorial Advisory Board.

Sanjay Garg, PhD

Most biopharmaceuticals are proteins or protein conjugates that are characterized by unique conformation in solution, which is essential for their function. Protein-conformation studies are valuable tools that help scientists understand the relationship between structure and function. These studies also help scientists evaluate biologicals’ comparability (e.g., in the event of process or formulation changes).The interest in conformational analysis is likely to increase in the near future as more companies develop biosimilars. The results of the analysis will help scientists compare generic biologicals with branded products. Approaches to the Conformational Analysis of Biopharmaceuticals surveys the technologies available for examining biopolymers.

 Approaches to the Conformational Analysis of Biopharmaceuticals, Roger K. Lundblad, Ed., CRC Press, Boca Raton, FL, 2010, 347 pp., ISBN: 9781439807804 

The book’s first two chapters introduce the topics of conformational analysis and the comparability of drug substances or formulations. Tables in Chapter Two summarize studies that evaluate the effect of chemical modifications, pressure, and temperature on protein conformation. They effectively encapsulate useful information about proteins, reagents, reaction conditions, results, and references and are quite useful for readers.Subsequent chapters offer excellent reviews of various instrumental techniques that reveal biomolecular conformation. These techniques include electrophoresis, affinity chromatography, size-exclusion chromatography, ultracentrifugation, differential scanning calorimetry, light scattering, luminescence, near- and mid-infrared spectroscopy, Raman and ultraviolet-visible spectroscopy, optical rotary dispersion, circular dichroism, nuclear magnetic resonance, chemical probes, and hydrogen exchange. Each chapter introduces one technique and enumerates its potential applications. Helpful tables list examples of applications and provide a wealth of references that can serve as good starting points for novices. 

Next, the book discusses chemical modifications of biopolymers. In this process, a chemical reagent is reacted with a protein’s functional groups. The author provides a long list of examples of chemical modifications with references. The chapter also explains the mechanism of action of various compounds.Scientists sometimes use immunological reactivity as a measure of biopolymers’ conformational integrity, and one of the book’s chapters describes this technique. It is essential to ensure that biosimilar products are nonimmunogenic. Likewise, products that have been reformulated or manufactured by modified processes must also be nonimmunogenic. This chapter’s discussion of using the enzyme-linked immunosorbent assay, a technique applied extensively to diagnostic products, to evaluate biopharmaceuticals’ immunological reactivity is particularly informative.

Other chapters explain how techniques such as limited proteolysis, crystallographic analysis, small-angle neutron and X-ray scattering, equilibrium dialysis, and enzyme kinetics can analyze proteins’ conformations. These techniques are not universally applicable. The chapter highlights the fact that they apply to certain cases and provides examples.

Finally, readers gain practical advice about developing an experimental approach for conformational analysis in the last chapter. The author gives practical tips about the need for documentation and about using multiple analytical approaches. A table compares various technological approaches, shows the amount of samples each requires, and indicates each approach’s limitations. The choice of assay is critical and should enable regulatory compliance.Overall, this book is an excellent reference for scientists who must select appropriate methods for conformational analysis. The text provides relatively brief notes about each technique, but supplements them with useful references and presents its explanations in language that is easy to understand. The book provides useful guidance for performing the conformational analysis of biopharmaceuticals, an application which will only become more important as follow-on biologics gain prominence. 

 is deputy head of the School of Pharmacy at the University of Auckland, New Zealand, and a member of 

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A timely new book explains techniques for conformational analysis.

Biopharmaceutical Form and Function

Recent incidents of drug contamination in the global supply chain have highlighted the importance of international quality standards. Information technology (IT) plays a role in ensuring drugs' quality, and common IT standards can be valuable tools. 

International IT Regulations and Compliance 

is a muchneeded addition to the literature about quality management and releated IT systems. The book covers topics ranging from quality standards and management systems, regulatory requirements, organization, audits, validation, laboratory systems, laboratory-information management systems (LIMS), and building-management systems. 

 International IT Regulations and Compliance, Siri H. Segalstad, Wiley, Hoboken, NJ, 2008, 338 pp., ISBN: 978-0-470-75882-3			

The first chapter describes quality standards and draws links between IT, quality, and best practices such as good manufacturing practice (GMP), good laboratory practice, and good clinical practice. Because these best practices require good process control, the IT systems that direct the processes also must be understood and controlled. The regulatory requirements for IT systems (e.g., 21 

Part 11 and EU GMP Part 11) are described in Chapter 2. 

The book's discussion of electronic records and signatures helps guide readers in developing these systems in the organization. Another chapter shows how IT security policy (e.g., the basic measures to protect data storage and transmission) helps mitigate threats. Although the discussion is informative, an appendix offering a general template for security policy could have been useful. 

Quality management systems (QMS) can help document processes, rather than having the knowledge stored in employees minds. Chapter 4 provides valuable information about creating QMS levels and assigning roles and responsibilities. The author explains QMS clearly in terms of a quality policy, manual, and standard operating procedures (SOPs), which helps the reader understand the big picture. SOPs are the basis for integrating an IT system with QMS, and Chapter 5 examines the details of generic and procedure-specific SOPs. 

Another chapter describes how the suppliers of a computerized system (e.g., software) must track their system-development life cycle within their quality system. The book clearly explains that pharmaceutical companies' IT departments are responsible for keeping the infrastructure, servers, clients, and hardware working. These departments must bear in mind the legal implications of IT systems for pharmaceutical, financial, patent, and human-resources applications. 

An organization's most important IT systems tend to be audited, and Chapter 10 examines audit types and  procedures. Table 10.1 provides a useful audit checklist that compares ISO 90003:2004 with Good Automated Manufacturing Practice (GAMP) 4 standards. Critical IT systems must be validated, and GAMP 4 is the only guideline that explains how to validate computerized systems. Table 11.2 is particularly useful because it summarizes common problems and explains how to handle errors during qualifications. 

Chapters 13–16 provide an excellent explanation of the qualification of IT systems. The process starts with the user requirement specification, which is the organization's view of the functions the new system should have. The IT department is responsible for operational and performance qualification, while end users are responsible for performance qualification alone.  

Chapters 17 and 18 deal with laboratory instrument and recording systems. It is vital to secure electronic laboratory notebooks for patent protection, among other reasons. The author offers practical information about securing LIMS and describes topics such as evaluating whether to build or buy a LIMS. 

Overall, this book is a good reference for everyone dealing with IT systems in a regulated environment. The style and content are targeted to entry- and middle-level professionals. The author  provides readers with a broad picture and strong overall understanding of IT systems.  

 is an associate professor and deputy head of the School of Pharmacy at the University of Auckland, New Zealand, and a member of 

's Editorial Advisory Board, tel. +64 9 373 7599 ext. 82836, 

A book guides readers through the regulatory requirements for computerized quality systems.

Quality in, Quality Out

To ensure drug purity and shield patients from harmful substances such as contaminated heparin, manufacturers and regulators rely on applied analytical science. Chemical metrology is the quantitative measurement of trace amounts of known, specific chemical compounds in complex matrices such as drugs, metabolites, and contaminants. The science's long history includes the invention of mass spectrometry in 1897, the separation of ions with different mass-to-charge ratios, and the development of the high resolution mass spectrometer. 

Trace Quantitative Analysis by Mass Spectrometry 

is an excellent contribution to chemical metrology because the authors draw on historical data, pictures, and stories to provide background for each chapter. This supplemental information makes for absorbing reading. 

Chapters 2 through 8 are appropriately labeled "Tools of the Trade," referring to practical aspects of mass spectrometry in a logical fashion. Chapter 2, "The Classical Tool," offers an excellent review of analytical and internal standards, balance, measurements, solutions, and calibration. 

 Trace Quantitative Analysis by Mass Spectrometry,  Robert K. Boyd, Cecilia Basic, and Robert A. Bethem, Eds., Wiley, Hoboken, NJ, 2008, 748 pp., ISBN: 978-0470057711			

Chapter 3 discusses the theories, basics, and advanced approaches of chromatography, presented in a way that is easy for novices to understand. The author brings the subject to life with pictures and the story of A.J.P. Martin and R.L.M. Synge, who won the Nobel Prize in chemistry in 1952 for inventing partition chromatography. 

The next chapter turns from theory to practice and describes immediate concerns about separation, details about sample-extraction methods, and chromatographic hardware. Perhaps to prepare readers for the frustrations of sample purification and extraction, the chapter is introduced by a quote about the nonreciprocal laws of expectations: "Negative expectations yield negative results, positive expectations yield negative results." 

A high level of confidence in identification and the peak purity of the analyte of interest are critical for quantitative analysis. Addressing these concerns, Chapter 4 talks about interfaces and ion sources for chromatography –mass spectrometry, including derivatization. The section offers an uncomplicated explanation of electron ionization, chemical ionization, matrix-assisted laser desorption and ionization, electospray ionization, and related techniques. These options support peak-purification identification with different analytes 

Chapter 6 examines mass analyzers and separation techniques such as tandem mass spectrometry and quadrupole instruments, which are critical for evaluation of trace metabolites. Chapter 7 is devoted to ion detection and data processing. The majority of current mass spectrometers detect and count ions using the electron-multiplier concept. This section explains the concept, which is the underlying principle for data integration. 

The chapters that follow the "Tools of the Trade" sections are devoted to practical aspects of method development. Chapter 9 explains fitting a method to a purpose and refers to the legal aspects of providing evidence for results when needed. Passages address issues such as balancing analytical thoroughness, available time and resources, analytical objectives, and requirements. 

The chapter about method validation and sample analysis in a controlled laboratory environment provides an algorithm that includes decision points that span from initial contact with a client to conducting the analysis. The section explains the details required for validation, followed by bioanalysis and documentation. 

is a wonderful book for beginner and intermediate students, analysts, and scientists keen on learning more about mass spectrometry. The authors' discussions of history and the evolution of relevant science make the text lively and engaging, no small achievement for a book about analytical science.  

 is associate professor and deputy head of the School of Pharmacy at the University of Auckland, Building 504, 85 Park Road, Grafton, Auckland, NZ, tel. +64 9 373 7599 ext. 82836, fax +64 9 367 7192, 

A book about pharmaceutical analysis engages the reader with history and unexpected asides.

A Peak in Mass-Spectrometry Literature

 helps analytical chemists understand the challenges and techniques related to the accurate identification and measurement of impurities in drug products. Eight of the book's chapters were contributed by experts from Big Pharma and the US Food and Drug Administration. 

The first two chapters provide solid introductions to the origin, control, and measurement of impurities in drug substances and products. 

A particularly interesting chapter covers the low-level measurement of potent toxins. The author describes the significant challenge involved in the analysis of these typically low- or sub-ppm-level impurities. The chapter explains gas chromatography (GC), high-performance liquid chromatography (HPLC), thin-layer chromatography, and other analytical techniques. He offers specific examples and reviews the available options.  

Contributing author Gary E. Martin offers a helpful algorithm for impurity identification in Chapter 5. His discussion of analytical techniques emphasizes the characterization of impurities. 

Chapter 6 discusses chromatography and on-line structure elucidation using spectroscopy. Its section about LC–mass spectrometry (MS), LC–nuclear magnetic resonance (NMR), and other related techniques is easy to understand, provides helpful examples, and describes many practical issues. 

An interesting map in Chapter 7 provides instructions for the preparative isolation of impurities. Impressive flow diagrams present information about impurity isolation, identification, work flow, method development scouting, and task performance. The diagrams help the reader put various tasks and operations in perspective. 

Chapter 8 examines the differences between analytical strategies for batch versus continuous processing with reference to techniques such as infrared, near infrared, NMR, and MS. 

Analysis of Drug Impurities, Richard J. Smith and Michael L. Webb, Eds., Blackwell Publishing, Oxford, UK, 2007, 288 pp., ISBN 978-1-4051-3358-6 

The book would have benefited from a full chapter each about the regulatory issues involved in the treatment of impurities and one about simple techniques such as HPLC. Overall, 

 is a strongly recommended reference for any laboratory that handles impurities.  

 Editorial Advisory Board, tel. 164 9 373 7599 ext. 82836, 

Regulators and industry professionals provide a guide for identifying and measuring impurities.

Charting a Path to Purity

The authors review patent literature that describes new developments in osmotic drug delivery such as pulsatile, delayed, and volume amplifier delivery devices.

An Update on Osmotic Drug Delivery

Evolution of an existing drug molecule from a conventional form to a novel delivery system can significantly improve its performance in terms of patient compliance, safety, and efficacy. These days,drug delivery companies are engaged in the development of multiple platform technologies to get competitive advantage, extend patent life, and increase market share of their products.