investigational new drug application

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Investigational New Drug

Application (INDA)

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INTRODUCTION REGULATORY ASPECT TYPE OF IND REQUIERMENT IND CONTENT OF IND IND AMENDMENT ANNUAL REPORT OF IND CONCLUSION

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WHAT I WILL TELL


What is INDA

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General introductionGeneral introduction

this data and information is generated this data and information is generated and gathered from three broad areas:and gathered from three broad areas:

Animal P’cology & Toxicology studiesAnimal P’cology & Toxicology studiesManufacturing informationManufacturing informationClinical Protocols & Investigator Clinical Protocols & Investigator InformationInformation


The regulations in 21 CFR 312 cover

procedures and requirements for Investigational New Drug Applications (INDs)

These regulations define the roles and responsibilities of FDA reviewers, IND sponsors, and clinical investigators

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Regulation


Sponsor A sponsor is an individual, company,

institution, or organization that takes responsibility for and initiates a clinical study (21 CFR 312.3(b), 312.50)

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Definitions


A sponsor is responsible for: Selecting qualified investigators Ensuring study monitoring Maintaining an effective IND, and Ensuring AE risk information is provided to the

FDA and investigators

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Sponsor


Investigator An investigator is an individual under

whose immediate direction the study drug is administered or dispensed. If a team is involved, the leader is the investigator; other team members are sub-investigators (21 CFR 312(b), 312.60)

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Definitions


Sponsor-Investigator A sponsor-investigator is an

individual who both initiates and conducts a study and under whose immediate direction the study drug is administered or dispensed. This person must follow the requirements pertaining to a sponsor and those pertaining to an investigator(21 CFR 312(b))

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Definitions


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IND Requirements


1. Commercial IND2. Emergency use IND 3. Treatment IND

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TYPE OF IND


To focus FDA’s attention during early phase of clinical research on assuring the safety of human test subjects.

To provide sponsors with a greater measure of flexibility in conducting Phase 1 trials.

To facilitate consultation between FDA & sponsors, especially after there is an indication that the new drug is safe and efficacious in humans.

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Objective


Cover Sheet (Form FDA 1571) Table of Contents Introductory Statement & General

investigational plan Investigator’s Brochure Protocols Chemistry, Manufacturing & Control

Information Previous Human Experience with the

Investigational Drug Additional Information

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IND Content Requirements21 CFR 312.23


The form is provided for basic

information like name of drug, submission date, sponsor identification, phase of proposed clinical investigation, sponsor commitments, identification of clinical monitor and safety evaluator, information regarding transfer of responsibilities to a contract research organization.

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Cover Sheet (form FDA 1571)


Drug Name®

IND table of contentsItem title volume/page Introductory statement & general investigational plan… (i) Introductory statement…. (ii) summary of previous human experience with drug……. (iii) If the drug has been withdrawn from Investigation/Marketing……

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Table of Contents


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iv) iv) General Investigational Plan…..General Investigational Plan…..5 Investigator’s Brochure…….5 Investigator’s Brochure…….6 Protocol……..6 Protocol……..7 Chemistry, Manufacturing & 7 Chemistry, Manufacturing & Control Information…Control Information… (a) Drug substance…………(a) Drug substance………… (b) Drug Product…………….(b) Drug Product……………. (c) Placebo (if applicable)…(c) Placebo (if applicable)… (d) Labeling…………………….(d) Labeling……………………. (e) Environmental Analysis ….(e) Environmental Analysis ….8 Pharmacology & Toxicology 8 Pharmacology & Toxicology Information…….Information…….


9)Previous Human Experience with the

Investigational Drug……. (i) Summary of Previous Human

Experience…. (ii) If the drug is a combination of drug previously investigated/marketed……. (iii) If the drug has been marketed outside

the United States……10 Additional Information (as applicable for radioactive drugs or drugs with

dependence or abuse potential)….

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It consists of four subsections:1st subsection: (introductory statement) Name of drug P’cological Class Structural formula Route of administration Broad objectives Planned duration of the proposed clinical

investigation04/12/23 20

Introductory Statement & General Investigational Plan:


2nd subsection: Brief summary of any previous human

experience with the drug, including investigational or marketing experience in other countries

3rd subsection: It is a statement as to whether or not the

drug has been withdrawn from investigation or marketing in any country for any reason of safety or efficacy


4th subsection: Brief description of overall investigational plan

for drug during the following year like: Indications to be studied, kinds of clinical trials to be conducted in first year


Sponsor must provide to all clinical

investigators, not required for sponsor investigators (21 CFR 312.55). It must include: Brief product description Pharm/tox summaries Previous human experience Description of anticipated risk and any special

monitoring needs Updates as appropriate

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Investigator’s Brochure (IB)


Drug Name®Investigator's Brochure

Table of contentsPage Introduction……………………..Chemistry………………………. Physical Properties…… How Supplied……………. Pharmacology…………………. Specific Effect Studies… General Studies………….


Toxicology……………………….. Acute Toxicity……………. Multidose Toxicity………. Special Toxicity Studies………Reproductive Studies…… Mutagenicity Studies…….Pharmacokinetics……………… Preclinical……………………. Clinical………………………….Clinical Trial………………………. Phase 1………………………… Phase 2/3… ………………….


Safety/Efficacy Overview Safety………………………….. Efficacy………………………..Possible Risks and Side Effects…References………………………….


Phase 1 protocol provides an outline of

investigation by specifying information such as estimated number of test subjects, inclusion/exclusion criteria and dosing plan

Phase 2 and Phase 3 protocols are detailed, describing all aspects of the studies, such that any deviation in a design if required, it can be established in the protocol from the beginning.

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5 Protocols


All the protocols are required to contain the following elements:

Statement of the objectives and purpose of the study

Patient inclusion/exclusion criteria Estimate of number of patients to be

studied Description of study design Dosing information including planned

maximum dosage and duration of individual patient exposure to the Drug

Description of the observations and measurements planned to fulfill the study objectives


Emphasis in Phase I is on identification and control

of raw materials and new drug substance, including information on any placebo as well

Even for Phase I, need enough information to assess safety

Extent of expected information increases as drug development proceeds

Throughout product development, good documentation of all manufacturing and testing steps is essential

Deficiencies in CMC information can result in clinical hold

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CMC Information


Previous human experience needs to be

included (if applicable) Additional information such as pre-IND

meeting minutes or critical references should be included as well

Serial numbering of pages of an IND is required (21 CFR 312.23(11)(e)) as this facilitates reference if the FDA has questions

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Other IND Items


21 CFR 312.30

A new protocol Safety or design related changes to an

existing protocol New investigator (notification is required

within 30 days of being added) These should be submitted to the FDA prior

to implementation IRB approval is needed prior to

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IND Protocol Amendments


21 CFR 312.31

Information amendments advise the FDA of: New tox, CMC or other technical information Notice of discontinuance of a clinical study

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IND Information Amendments


If a sponsor notify any unexpected fatal / life

threatening experience associated with the use of the drug requires to notify the FDA by telephone no later than 3 working days after receipt of the information, followed by a written report within 10 days.

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IND Safety Reports:


21 CFR 312.33

To be submitted within 60 days of the anniversary of “in effect” date

Include enrollment, demographic and conduct status information for each study

Adverse event summaries (safety reports, deaths, dropouts)

Drug action information Preclinical study status information

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Annual Reports


CMC change information Revised/updated investigator brochure with

revisions described Foreign marketing experience Outstanding business with the FDA

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Annual Reports (cont’d)


It is option of a sponsor to withdraw an IND at

any time without prejudice.On withdrawn, sponsor must notify the FDA.

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Withdrawal of an IND


Two major outcomes from the IND discussion are: 30 days after an IND is submitted to the FDA,

if the sponsor has not heard anything from the FDA it can be assumed that the drug is not on a clinical hold and clinical trials may be started

The Investigator’s Brochure, which will be used during that important first clinical study and in every clinical study thereafter, acts as the approved labeling for the drug while it is under an IND

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Conclusions


1.www.fda.gov/cder/about/history/time1.htm2.Remington the science and practice of

pharmacy, 20th edition, Lippincott,Williams & Wilkins, page no: 930-943

3. New Drug Approval Process: second Edition, Revised and Expanded, edited by Richard A. Guarino page no: 39-64, 243-263

4.www.fda.gov/cder/handbook/indbox.htm5.www.fda.gov/cder/handbook/ndabox.htm6.www.fda.gov

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List of references


investigational new drug application

Documents

study drug

combination of drug

ind requirements

ind sponsors

effective ind

treatment ind

commercial ind

clinical investigators