agencies, and academia (Bjornsson et al., 2003; Tucker et al., 2001). A detailed
description of GLP can be found on the FDA guidance website, Good
Laboratory Practice for Nonclinical Laboratory (FDA, 2003d) (Table 7.1). On
the contrary, like any clinical study, human ADME studies should follow the
ICH guidance ‘‘Good Clinical Practices’’ (GCP) (ICH, 1997) (Table 7.1). This
document describes the responsibilities and expectations of all participants in
the conduct of clinical trials and covers aspects of monitoring, reporting, and
archiving of clinical trials and incorporating addenda into the essential
documents and into the investigator’s brochure.
7.2.6 Regulatory Submission Format and Content
7.2.6.1 Investigational New Drug Application (IND) The FDA regulations
require a sponsor to submit an IND to the agency before the initiation of
human studies in the United States for an investigational drug. The general
principles underlying the IND submission and the general requirements for
IND content and format are published in the CFR Title 21, Part 312
Investigational New Drug Application (FDA, 2003a). These documents
suggest including a summary of the pharmacological effects and mechanism(s)
of action of the drug in animals, and information on the absorption,
distribution, metabolism, and excretion of the drug, if known, in the section
of pharmacology and drug disposition of IND submission. The FDA guidance
‘‘Content and Format on Investigational New Drug Applications for Phase I
Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-
derived Products’’ (Table 7.1) clarifies requirements for data and data
presentation outlined in 21 CFR 312.22 and 312.23.
7.2.6.2 Investigator’s Brochure (IB) The IB is a collection of the clinical and
nonclinical data on the investigational product that support the rationale for
the proposed clinical trial and the safe use of the product. The IB is provided to
investigators and others involved in clinical trials. As a part of the IND
submission and the clinical trials applications in the European Commission,
the IB is also submitted to regulatory authorities. The IB document should be
updated annually to include new clinical and nonclinical information and
should be presented in the format of summaries. The ICH guidance (E6, Good
Clinical Practice, Table 7.1) (ICH, 1997) describes the content and format of IB
documents. It suggests including a summary of the pharmacokinetics and
product metabolism in animals in the section of Nonclincal Studies, and a
summary of the pharmacokinetics and product metabolism in humans in the
section of Effects in Humans.
7.2.6.3 New Drug Application (NDA) (FDA, 2003b) The FDA document
‘‘Applications for FDA Approval to Market a New Drug’’ (CFR Title 21,
314), sets forth procedures and requirements for the submission to, and the
review by, the FDA of applications to market a new drug. The content and
210 REGULATORY CONSIDERATIONS OF DRUG METABOLISM AND DRUG