Contents Of An Initial

The standard contents of an initial IND is described specifically in the regulations in Part 312. These contents are also listed in the FDA standard covering form for INDs, i.e., Form FDA 1571. Further explanatory guidance on the content and format of INDs can be found in regulatory documents (1,2).

The standard contents of an initial IND are listed in Table 1. The concept underlying this contents of an initial IND can be readily understood if you con-

Table 1 Standard Contents of an Initial IND

Item number Contents of section

Item 1 Form FDA 1571

Item 2 Table of Contents

Item 3 Introductory Statement & General Investigational Plan a. Introductory Statement b. Summary of Previous Human Experience c. Withdrawal from Investigation or Marketing d. Overall Plan for Investigations Item 4 Reserved

Item 5 Investigator's Brochure

Item 6 Protocol

Item 7 Chemistry, Manufacturing and Control Data a. Drug Substance b. Drug Product c. Description of Placebo d. Labeling e. Environmental Assessment Item 8 Pharmacology and Toxicology Data a. Pharmacology b. Toxicology

Item 9 Previous Human Experience

Item 10 Additional Information a. Drug Dependence and Abuse Potential b. Radioactive Drugs c. Other Information sider the contents within the six technical sections that comprise all regulatory submissions. The six technical sections of U.S. drug regulatory applications (i.e., Pharmacology & Toxicology, CMC, Clinical, Microbiology, Statistics, and Human Pharmacokinetics & Bioavailability) are illustrated in Fig. 1. In Fig. 2, the items in an initial IND are shown within the technical sections. This information and its associated documentation can be extensive. In the 1980s and 1990s, until 1996, initial INDs for new chemical entities presented this information in sufficiently complete detail to enable a comprehensive review, including review of raw data, not simply summaries of data. Typically, an initial IND would comprise 4000-6000 pages (e.g., 10 to 15 volumes of 400 pages per volume). For such initial INDs, the nonclinical pharmacology and toxicology information typically comprised the largest portion of the IND.

Regulatory reform efforts in the 1990s led to the FDA's issuance of its guidance (in November 1995) regarding streamlining the contents of an initial IND to specifically support an initial Phase I study (2). FDA's guidance states that ''if the guidance specified in this document is followed, IND submissions for Phase 1 studies should usually not be larger than 2 to 3, three inch, three-ring binders'' (i.e., approximately 1200-1800 pages). Obviously, successful implementation of this guidance could lead to substantial reduction in documenta-

Drug Regulatory Applications
Figure 1 Six technical disciplines that comprise all drug regulatory applications in the United States.
Figure 2 Diagrammatic representation of each item in an initial IND.

tion needed for an initial IND. Given the youth of this new guidance, its implementation bears close observation.

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