INVESTIGATIONAL NEW DRUG (IND)

 INVESTIGATIONAL NEW DRUG (IND)

INTRODUCTION:

Before post-marketing surveillance and after the completion of all the clinical trial phases being completed successfully, the market authorization holder(s) sends a request to Food and Drug Administration (FDA) for an Investigational Drug Application (IND) to begin human clinical trials and to shape the drug experimentally globally for clinical investigation. The Food and Drug Administration (FDA) and European Medicine Agency (EMA) are the regulatory bodies to permit the use of investigational drugs. To permit the use of investigational drugs, documents must be submitted and reviewed by the health authority. In the US the submission is called Investigational New Drug application. To apply INDs regulations are described in 21CFR parts 50,56 and 312.

WHAT IS IND?

                  An Investigational New Drug Application(IND) is a submission to FDA requesting permission to initiate the study of New Drug Product. IND is that the results of a successful preclinical trial. The Sponsor advances to the next stage of drug development (Clinical Trials).

IMPORTANCE OF IND:

• IND helps us to the next stage of drug development i.e clinical trial.

• It plays a vital role in the development of new compounds which exhibit pharmacological activity.

• IND can be an alternative in a life-threatening situation when no standard acceptable therapy is available.

• It helps us to obtain pharmacological and toxicological information on new drugs.

• It helps the sponsor to determine the product is safe for initial use in humans.

CONTENT OF IND:

• Pharmacology and Toxicology Studies- An evaluation to check whether the product is safe for initial testing in humans.

• Manufacturing Information- Name of the manufacturer, Composition, stability used for manufacturing the drug.

• Clinical Protocol and Investigator Information

FORMAT OF IND:

Current regulations containing the overall principles and requirements for the IND submission at 21CFR 312.22 and 312.23. It includes the subsequent sections:

A. Cover Sheet (FDA Form -1571) [21 CFR 312.23(a)(1)

B. Table of Contents( 21 CFR 312.23(a)(2)

C. Introductory Statement and General Investigational Plan (21 CFR 312.23(a)(3))

           This should contain a detailed description of the investigational product ( Name, excipients, dosage form, and route). The regulations described here should be brief. Generally, two to three pages must suffice. When it is for a single trial, the data must be focused on describing and supporting the trial.

D. Investigator’s Brochure (21CFR 312.23(a)(5):

                 All the information regarding the investigational drug should be stated in the investigator's brochure. If any further information is required sponsors are referred with this document.

E. Protocols ( 21CFR 312.23(a)(6):

          Protocol copy should be submitted for the initiation of clinical trials. It states that outline of the Phase 1 trials should be directed and must include the subsequent information:

              i) Number of subjects participating within the trial.

              ii) Inclusion and exclusion criteria.

              iii) Description of Dosing plan ( Dosage, Duration, Method used)

F. Chemistry, Manufacturing and Control Information (21CFR 312.23(a)(7):

       It highlights the graded nature of the CMC of the drug. In every phase of the trial adequate information should be submitted to assure the quality, purity, identification of the drug. Stability data are also submitted to demonstrate the drug has acceptable physio-chemical properties It includes:

         i) Chemistry and Manufacturing

        ii) Drug Substance

        iii) Drug Product

       iv) Placebo used in the proposed clinical trial

       v) Labelling copies should be given to the investigator.

       vi) Claim for categorical exclusion or submission of conservation assessment.

G. Pharmacology and Toxicology Information (21 CFR 312.23 (a)(8):

          The sponsor should submit detailed pharmacological and toxicological information about the drug. It contains the description of the pharmacological effects and MAO of the drug in animals, and information about ADME of the drug, Toxicology information including the in-vivo and invitro should be reported.

H. Previous Human Experience with the Investigational Drug (21 CFR 312.23(a)(9):

        If there is previous human experience, it may be presented in a summary report. Individual study reports should not be routinely submitted.

I. Other Information (21CFR 312.23(a)(10):

            Sponsor-investigator must submit other types of information about the drug dependence, radioactive drug if the investigational drug is not approved.

J. Relevant Information (21 CFR 312.23 (a)(11):

      Relevant information about the investigational drug should be stated on the manufacturer, the model of the device to be employed, and the general description of relevant conditions of use.

 WHO SHOULD FILL THE IND?

         Sponsor-investigator is required to fill the IND form. The sponsor should wait for 30 calendar days after submission to start the trial.

WHEN IT WILL BE SUBMITTED?

An IND application is required to be submitted when the research may be a clinical investigation, and therefore a clinical investigation isn’t exempted from IND regulations. The application should be submitted within 60 days of the annual date.

TO WHOM IND SHOULD BE SUBMITTED?

            IND is submitted to Food and Drug Administration

    After the submission of IND, the FDA has 30 days from the day of IND receipt to decide whether the proposed clinical trial should proceed or not. In this time period, the IND submitted to FDA is assigned to various divisions of the Center for Drug Research and Evaluation of FDA for its review and evaluation.

      If all the necessities for FDA approval are satisfied then IND is granted.

CONCLUSION:

          The sponsor's primary goal is to combine the information obtained from Pharmacology, Pharmacokinetics, Non-clinical Toxicology to evaluate the safety and efficacy of a new drug in humans, taking the required precautions to safeguard the study subject safety. IND information is mandatory to support the initiation of a clinical trial of a new drug in humans. Significant time and resources are required to enable a successful submission and approval.

Written By :

K.Meghana, M.Pharm

ClinoSol Student ID:267/1021

G.Tanushri, B.Pharm

ClinoSol Student ID : 277/102