Abstract
This book is intended to “introduce the concepts and processes from drug discovery to marketing approval by regulatory authorities.” Although a rather ambitious goal, the author succeeds in providing a very broad overview of the drug development process. The text is generally written on a very basic level (eg, it explains what a drug is, what a receptor is) and therefore is probably best suited for undergraduates who want a bird's-eye view of the drug development process.
The order of presentation of the various chapters is logical in that it generally follows the drug discovery/drug development timeline. Chapter 1 sets the stage for the rest of the book by defining some basic terms (eg, What is a drug? What is a patent?), outlining the drug development process, and introducing the reader to the pharmaceutical industry and the high cost of drug development. Chapter 2 describes receptors as drug targets within the context of how drug companies may identify potential disease targets and then pursue potential mediators (inhibitors or agonists) to interact with these targets. The remaining chapters then cover topics such as drug discovery for small and large molecules (Chapters 3 and 4), preclinical studies (Chapter 5), clinical studies (Chapter 6), regulatory authorities (Chapter 7), regulatory applications (Chapter 8), Good Manufacturing Practices: requirements and drug manufacturing (Chapters 9 and 10), and future perspectives (Chapter 11). The book also contains 4 appendices involving the history of drug discovery and development; a brief primer on cells, nucleic acids, genes, and proteins; selected drugs and their mechanisms of action; and an outline of the Food and Drug Administration's (FDA's) proposed organization of pharmacology/toxicology reviews. Also included is a list of acronyms and a glossary.
Throughout the book, the author makes liberal use of “exhibits,” or sidebars, to elaborate on or provide examples of issues discussed in the text. In many cases, these exhibits serve a good purpose in offering an easy explanation of a topic, but in other cases, the information in the exhibit is probably too technical to be useful to the reader (eg, Exhibit 3.6 provides mathematical equations to describe X-ray crystallography). Sometimes, it is not clear why a topic is covered in an exhibit (eg, Exhibit 5.6 discusses the Ames test, but no rationale is provided for selecting this assay over other preclinical assays for further explanation).
The most important caveat with this textbook is that it contains a number of errors and omissions, some of which are relatively minor and inconsequential, but others that have more impact. Minor errors include referring to cimetidine as Zantac (rather than Tagamet), stating that drug-receptor interactions are specific and reversible (yet, many interactions are nonspecific and some are irreversible), and referring to anti-obesity and anti-smoking drugs as “lifestyle” drugs. Anti-obesity and anti-smoking agents target conditions that are associated with significant morbidity and mortality and, in my opinion, should not be grouped with anti-wrinkle creams or hair loss therapy as lifestyle drugs.
Examples of more significant errors include stating that a positive response from the FDA is required before clinical trials may begin (Chapter 6). Clinical trials may commence 30 days after an investigational new drug (IND) application is filed with the FDA; a response from the FDA is not required. Chapter 8 notes that an IND is filed for each phase of clinical trials (Phases I, II, III); however, these phases of drug development are conducted under a single IND.
In several places, the text is incomplete in its presentation. For example, the toxicology section of Chapter 5 outlines many of the required preclinical tests in drug development, but it does not mention preclinical testing for potential adverse drug effects on QT intervals, an increasingly important consideration in preclinical studies. Also, preclinical testing for photosensitivity potential is not mentioned. In Chapter 6, Exhibit 6.8 is supposed to “summarize the required information for a [clinical] protocol,” but it omits many of the key required elements (eg, study objectives, statistical analysis plans). Finally, the text does not mention risk management plans, a concept that must be addressed in essentially all new drug applications (NDAs) to the FDA. Omissions such as these are significant detractors to the value of this book.
One other important item deserves comment: the common technical document (CTD). The CTD represents an agreement between the US, European, and Japanese regulatory agencies to accept marketing applications (ie, NDAs in the US) in a single format or structure. Previously, each regulatory agency required different formats for marketing applications. Given the tremendous size of a typical marketing application, this meant that companies had to expend significant resources and time rewriting and repackaging the same data into different formats for each country's application. Therefore, the CTD represents an attempt to streamline the work required to submit marketing applications to different countries. Although the CTD is described very briefly in Chapter 7, in Chapter 8 the author inexplicably outlines the obsolete formats for NDAs and European applications. This may be confusing or misleading to those unfamiliar with current regulations.
I have pointed out a number of shortcomings in this text, but I should also note that the author has done an admirable job of outlining the many processes involved in bringing a compound from discovery through animal testing, human clinical trials, and, finally, to regulatory application. A significant challenge in writing a textbook such as this one is the relatively rapid changes that occur in the regulatory environment and in the tools used in drug development. However, each chapter has a list of suggested additional readings, many of which are Web sites. This would allow the interested reader to gain further details on the many topics covered in this text.
As previously stated, this book is probably best suited for undergraduates who are interested in a very broad introduction to the drug development process. However, due to the various errors and omissions, it would not be appropriate for those who work in the industry or as a textbook for training those interested in a career in industry.