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U.S. Department of Health and Human Services

Drugs

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IND Applications for Clinical Investigations: Non-clinical Components

The non-clinical components of an IND application include Chemistry, Manufacturing, and Control (CMC) information for the investigational new drug and Pharmacology and Toxicology (PT) information (i.e., animal toxicology studies) conducted with the investigational new drug.

To avoid duplicating efforts, the existing information already submitted to FDA as part of previous Investigational New Drug applications or New Drug Applications may be referenced by new IND applicants (e.g., investigators-sponsors of subsequent IND applications with the same investigational drug). The existing information most frequently referenced by IND applicants includes available CMC information and information from animal toxicology studies conducted to date. Other materials such as Investigator’s Brochure, Environmental Assessment, Previous Human Experience, or other relevant information may also be referenced.

The two most common situations when IND sponsors choose to reference data from other applications include circumstances when: (a) the proposed investigational drug is the subject of another already existing IND application and (b) the proposed investigational drug is a marketed product.


a) IND application with an investigational new drug or biological product that is the subject of another existing IND application:

In order to refer to the existing information about an investigational drug submitted under another IND application, the investigator-sponsor may obtain a Letter of Authorization from the existing IND application’s sponsor (e.g., product’s manufacturer). Such Letter of Authorization will grant a right of reference to the existing information which, in essence, will result in two permissions:

  1. For the current IND applicant: to refer in their current IND application to the proprietary information about the investigational new drug already submitted to FDA under the previously submitted existing IND application, and

  2. For FDA: to review the information already submitted to FDA under the existing IND application and, without disclosing this information to the current IND applicant, to determine whether the referenced information is sufficient to address the needs of the current IND application. 

    For example, if an investigator submitting an IND application plans to conduct a clinical study with an investigational product which they intend to obtain from the product’s manufacturer, then the CMC and/or PT information of the investigator’s IND application may be referenced to the existing manufacturer’s IND application, provided that the Letter of Authorization has been obtained. A need for additional non-clinical studies may be obviated if the animal toxicology studies already submitted to FDA satisfactorily address all potential safety concerns and the safety margin for the dose, route, frequency of dosing and duration of treatment proposed in the investigator’s intended clinical study.  

     

b) IND application with an approved marketed drug or biological product:

With regard to referencing the available information previously submitted and reviewed by FDA as part of a marketing application, two examples may be considered:

  • Example 1 (applies to both CMC and Pharmacology and Toxicology): The proposed investigation may rely on previous FDA’s findings of acceptability of CMC and Pharmacology and Toxicology information for the approved product. If the proposed dose, route, frequency of dosing and duration of therapy do not exceed the approved labeled dosing regimen, the investigator-sponsor may provide the product’s labeling information and state in the non-clinical section of the application that they believe their IND application may rely on the previous FDA’s acceptance of the CMC and/or Pharmacology and Toxicology information related to the approved marketed drug intended for this investigation. FDA will then determine during the review of the IND application (30 days) whether additional information is needed.

  • Example 2 (applies to CMC): The proposed investigation may rely partially on the information available from the manufacturer’s Drug Master File (DMF). The investigator-sponsor of the IND application may obtain a Letter of Authorization from the current manufacturer of the marketed product permitting to reference the manufacturer’s DMF. FDA will then review the referenced DMF and determine whether additional information is needed.