Nonclinical research

Nonclinical safety pharmacology studies submitted to regulatory agencies are outlined in ICH Guidance S7A (2001), and the basic package includes evaluation of a drug candidate s effects on the central nervous system, respiration, and the cardiovascular system. Cardiovascular system evaluation includes assessment of cardiac function and cardiac electrophysiological activity. 

While a nonclinical development program is informative and important, no amount of nonclinical research can predict precisely what will happen once the candidate drug is given to humans. Therefore, a clinical development program is also necessary. The clinical development program builds in many meaningful ways on the results from the nonclinical development program. 

Clinical development programs consist of a variety of preapproval clinical trials, all designed for a specific purpose of revealing particular information concerning the investigational drug s safety and efficacy. 

A common system of categorization for preap-proval clinical trials includes Phase 1, Phase 11, and Phase 111 clinical trials (Phase IV clinical trials are conducted postapproval to collect additional information about a marketed drug). Phase 1, 11, and 111 clinical trials can be summarized as follows  

Chapter 2 The role of clinical trials in new drug development 

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Assay used for basic research Nonclinical research for nondiagnostic purposes Labeling requirements only... 

Nonclinical research provides very useful information and plays a considerable role in the successful development of a new drug. It is also required by current regulatory statutes. Nonetheless, no matter how meticulously, rigorously, and comprehensively nonclinical testing is conducted, no animal model is a perfect model of the drug s actions and effects in humans. Therefore, in addition to an appreciation of the usefulness of nonclinical data, it is valuable to have an appreciation of their limitations and of statistical considerations of particular pertinence to toxicological data. 

As was noted in Chapter 4, pharmacokinetic and pharmacodynamic effects are studied in nonclinical research. These topics are also of critical importance in clinical investigations. A drug s pharmacokinetics and pharmacodynamics are of considerable interest to clinicians who may prescribe the drug to patients once it is approved. Meaningful decisions about a drug s optimal use can only be made with an understanding of the time course of events that occur after the drug s administration, and both pharmacokinetics and pharmacodynamics are concerned with this time course. By consideration of the pharmacokinetic processes of absorption, distribution, metabolism, and excretion (ADME), the... 

In nonclinical research, attention to detail is every bit as important as in clinical development. As Gad (2006) observed, the importance of nonclinical laboratory studies demands that they be conducted according to scientifically sound protocols and with meticulous attention to quality. ... 

After a pharmaceutical or biotechnology company, commonly referred to as the sponsor, has decided to use CROs to support some of the nonclinical research... 

The final strategy, the special study strategy, is used by some sponsoring companies to place single or a few nonclinical research studies with a CRO. If a company s internal resources are usually, but not always, sufficient to meet their nonclinical drug development needs, this strategy provides a means to have a critical study completed to meet the timeline on a drug development plan. How-... 

Descriptive title of the nonclinical research study Purpose of conducting the study Where and by whom the study is to be conducted Company that is sponsoring the study Sponsor s agent who is responsible for monitoring the study CRO senior staff who will be responsible for the various aspects of the study... 

What is the role of nonclinical research in new drug development ... 

For various reasons there are often participants in a trial for whom a complete set of data is not collected. This is the province of missing data. When conducting efficacy analyses we need to address this issue, and the way(s) in which it is addressed can influence the regulatory reviewers interpretation of the analyses presented. The issue of missing data is problematic in clinical research because humans have complex lives. Human participants may choose to leave a study early or be unable to attend a specific visit, both situations leading to missing data. Nonclinical research involves tighter experimental control in which the subjects (animals) do not have the ability voluntarily to leave the study early. 

This chapter describes the biological aspects of the nonclinical research programs of the drug development process. The chapter has been organized along the timeline for the nonclinical drug discovery and development process, with the major subsections being... 

After a pharmaceutical or biotechnology company, commonly referred to as the sponsor, has decided to use CROs to support some or all of the nonclinical research effort in a drug development program, management or the project team responsible for the development of the drug candidate assigns individuals to identify and select the appropriate CROs. The steps in a selection process should include, but are not be limited to ... 

In the preselected strategy, the first choice of many large and midsized pharmaceutical houses, a limited number—usually three to six—of CROs are prequalified to support a company s possible nonclinical drug development needs. The qualification process usually includes a detailed site visit to review the CRO s facilities, staff, and GLP compliance and to determine which types of nonclinical research studies, such as... 

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