The investigational new drug application

The regulations pertaining to INDs are located in 21 CFR 312 and provide detailed guidance for both content and format. Interestingly, a sponsor does not hear from the FDA if the FDA s review is positive. The FDA reviewers have 30 days to respond to the sponsor following submission of the IND. If the sponsor has not been contacted in that window, they have implied permission to commence the clinical development program described in the IND. 

In scientific terms, the purpose of an IND is to provide detailed documentation that will allow the FDA to conclude that it is reasonable for the sponsor to proceed to clinical trials. Generally, this includes data and information in four broad areas  

Chemists are responsible for reviewing the chemistry and manufacturing control (CMC) sections of the IND. These sections address issues related to drug identity, manufacturing control, and analysis. Drug manufacturing and 

The CDER has several offices, including the Office of Pharmacoepidemiology and Statistical Science. This office contains the Office of Biostatistics. One of the Office of Biostatistics responsibilities is to develop statistical and mathematical methods to enhance the drug review process in various areas, including  

The Office of Biostatistics has taken the lead in the development of several guidance documents on specific topics, including ICH E9, Statistical Principles in Clinical Trials, and ICH E10, Choice of Control Groups in Clinical Trials. It is advisable for sponsors to follow these guidances. 

An investigational new drug is a new chemical-based, biologic or biopharmaceutical substance for which the FDA has given approval to undergo clinical trials. An IND application should contain information detailing preclinical findings, method of product manufacture and proposed protocol for initial clinical trials (Table 4.9). 

In some instances, the FDA and drug sponsor (company/institution submitting the IND) will agree to hold a pre-IND meeting. This aims to acquaint the FDA officials with the background to/content of the IND application, and to get a feel for whether the IND application will be 

Proposed trial detail and protocol (general investigational plan) 

Chemistry (or biology, as appropriate) manufacturing, and control detail Pharmacology and toxicology data 

Any previous human experience regarding the drug substance Any additional information 

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A standard toxicology package was developed for tasidotin for filing the Investigational New Drug Application with the Food and Dmg Administration (FDA). Single-dose studies under the proposed route of administration (IV) were initiated... 

Information provided by the sponsor relating to Item 7 is often incomplete. Provide the Investigational New Drug Application (IND) or New Drug Application/Biologics License Application (NDA/BLA) numbers if they are available to you. 

Guarino, R.A. The investigational new drug application and the investigator s brochure. In New Drug Approval Process, 3rd Ed. Marcel Dekker, Inc. New York, 2000 100, 74-75. 

Before any clinical study can be carried out in the USA, an exemption from the need to hold an NDA must be obtained from the FDA. The detail required on the packaging provided in the Investigational New Drug Application (IND) depends on whether the study is in an early phase (Phase I) of testing or in the late phase (Phase III). It is recognised that at the early phases, an outline of the packaging used and an indication of the appropriate stability studies which have been initiated may well suffice, but at Phase III the information supplied should be directed towards fulfilling the requirements of the full NDA. 

Even a brief description of the regulatory requirements to initiate studies in humans is beyond the scope of this chapter. In the United States, the Investigational New Drug Application (IND) and, if desired, pre-IND meeting represent both the main regulatory barrier to initiate studies in humans and the first opportunity to educate regulators about the drug candidate. 

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