INVESTIGATIONAL NEW DRUG

APPLICATION

(IND)

PRESENTED BY:

NUTHAN

INTRODUCTION:

DEFINITION OF IND:

An IND is a submission to the food and drug administration (FDA) requesting permission to initiate a clinical study of a new drug product.

The Federal Food , Drug and Cosmetic act requires that drugs have an approved marketing application before they can be shipped in interstate commerce.

The IND application allows a company to initiate and

conduct clinical studies for their new drug products.

The IND application provides the FDA with the data

necessary to decide whether the new drug and the

proposed clinical trial pose a reasonable risk to the

human subjects participating in the study.

WHEN DO WE NEED AN IND :

An IND is required any time when we want to conduct

a clinical trial of an unapproved drug.

An IND would be required to conduct a clinical trail if

the drug is :

A new chemical entity , not approved for the

indication under investigation in a new dosage form.

Being administered at a new dosage level.

In combination with another drug and the combination

is not approved.

All clinical studies where a new drug is administered

to human subjects , regardless of whether the drug

will be commercially developed , require an IND.

WHEN DO WE NEED AN IND : (cont..)

WHEN DO WE DON’T NEED AN IND :

An IND is not required to conduct a study if the drug :

Is not intended for human subjects , but is intended

for in vivo testing or lab research animals (non clinical

studies).

Is an approved drug and the study is within its

approved indication for use.

CATEGORIES OF IND :

COMMERCIAL IND : Goal is to obtain marketing approval for a

new product.

NON-COMMERCIAL IND : It includes :

INVESTIGATOR IND : In this case ,the physician is both the

sponsor and investigator.

EMERGENCY IND : FDA authorize immediate dispensing of a

non-approved drug in a life threatening situation when no standard

acceptable therapy is available.

TREATMENT IND : FDA will permit investigational drug to be

used to treat a serious or life threatening disease or if there is no

comparable alternative drug available.

PRE-IND MEETING :

A meeting between the sponsor and the FDA frequently

is useful in resolving questions and issues raised during

the preparation of an IND.

The FDA encourages such meetings to the extent that :

They aid in the solution of scientific problems and

To the extent that the FDA has available resources.

Most issues and questions are usually related to the

Design of animal studies needed to initiate the clinical

trials.

The scope and design of the initial study in humans.

Meeting should be scheduled to occur within 60 days

of the FDA’s receipt of the written request for the

meeting.

A briefing document is required at least 4 weeks prior

to the meeting.

The briefing document should provide summary of

the information related to the product.

PRE-IND MEETING : (Cont..)

ESSENTIALS OF AN IND :

IND must present adequate information to permit the

FDA to evaluate the drug’s suitability for use in the

proposed clinical study.

The central focus of the initial IND should be the

general investigational plan and the protocol for the 1st

proposed human study.

To assure that the human subjects who participate in

the proposed study will not be exposed to unreasonable

and significant risk.

CONTENT AND FORMAT OF AN IND

APPLICATION :

The content and format of an initial IND is laid out in 21

CFR(code of federal regulations) part 312 .

1. Cover sheet – 312.23(a)(1) FDA form 1571

2. Table of contents – 313.23(a)(2)

3. Introductory statement and general investigational plan –

312.23(a)(3)

4. Investigators brochure – 312.23(a)(5)

5. Clinical protocol – 312.23(a)(6)

6. Chemistry , manufacturing and control data – 312.23(a)(7)

7. Pharmacological and toxicological information –

312.23(a)(18)

8. Previous human exposure – 312.23(a)(9)

9. Additional information – 312.23(a)(10)

10. Relevant information – 312.23(a)(11)

CONTENT AND FORMAT OF AN

IND APPLICATION : (Cont..)

FDA FORM 1571:

1.Name of the sponsor :

He/she is the person who takes responsibility for and initiates a clinical investigation.

May be a pharmaceutical company, a private or academic organization, or an individual.

2.Date of submission :

It is the date when the application is mailed to FDA.

3. Address :

It is the address to which written correspondence from FDA should be directed.

4. Telephone number :

It is the number where the sponsor is usually

available during normal working hours. A

telephone number must be provided.

5. Name(s) of Drug :

List the generic name(s) and trade name, if

available. Also, state the dosage form(s).

FDA FORM 1571: (Cont..)

6. IND Number :

If an emergency IND number was previously assigned by FDA, or the Form FDA 1571 is being included with an amendment to the original IND, then that IND number should be entered here; otherwise, the space should be left blank.

7. Indication.

8. Phase of clinical investigation to be conducted.

9. list number of all investigational new drug application.

10. Serial number.

11. Contents of application.

FDA FORM 1571: (Cont..)

12.Name and title of the person responsible for monitoring

the conduct and progress of clinical investigation

13. Is any part of the clinical study to be conducted by CRO

13. Name and title of the person responsible for review and

evaluation of information relevant to the safety of drug

14. Name of sponsor’s authorized representative

15.Signature

16.Address

17.Telephone no.

18.Date

FDA FORM 1571: (Cont..)

INTRODUCTORY STATEMENT:

Description of the investigational drug

All active ingredients

Drug’s pharmacological classification

Structural formula

Route of administration

Summary of previous human experience

Formulation of dosage forms

Objective and planned duration of proposed clinical investigation.

INVESTIGATIONAL PLAN:

Description of clinical studies planned for the

experimental drug

Purpose of the study

Indication to be studied

Types of trials to be initiated

Number of study subjects

Risks involved

INVESTIGATORS BROCHURE:

Structural formula of drug.

Summary of pharmacological , toxicological ,

pharmacokinetic effects in animals.

Safety and efficacy

Purpose of study

Dose / dose frequency

Monitoring procedures

CLINICAL PROTOCOL:

A clinical protocol describes how a particular clinical

trial is to be conducted.

It describes

the objectives of study

the trial design

how subjects are selected

how the trial is to be carried out

It should contain the following elements:

A statement of the objective and purpose of study.

Name , address and qualification of each investigator

participating in the study.

Name and address of each clinical site.

Study subject inclusion and exclusion criteria.

Estimate of the number of subjects to be enrolled in the

study.

CLINICAL PROTOCOL: (Cont..)

CHEMISTRY, MANUFACTURING AND

CONTROL DATA:

Determines the adequacy of methods used to manufacture and assay investigational compound

Safety concerns

Describe drug substances

Method of preparation

Reagent and solvents

Acceptable limits and analytical methods to ensure quality and purity of drug.

PHARMACOLOGICAL AND

TOXICOLOGICAL DATA:

Pharmacology and drug disposition

Integrated toxicology summary

Previous human exposure :

Marketed (foreign) or previously tested in

humans.

FDA REVIEW OF THE IND:

Once the IND is stamped as received ,it is sent to the review division within CDER(Center for Drug Evaluation and Research).

On arrival at the review division , it is critically evaluated by several

reviewers of

Chemistry

Biopharmaceutics

Medical

Statistics

Microbiology

Pharmacology /toxicology sections

All these areas review the data submitted with the

primary purpose to ensure safety of the individual

enrolled in the study.

Once an IND is submitted, the study can’t be initiated

until a period of 30 days.

If there are any major issues relating to the safety of

the volunteers in the proposed study , the FDA can

institute a clinical hold.

FDA REVIEW OF THE IND:

(Cont..)

IND ANNUAL REPORTS:

Sponsors should submit an annual report that provides

the FDA with a brief update on the progress of all

investigations included in the IND.

It should contain the following:

Individual study information.

Summary of the study.

Listing of any significant foreign marketing

developments with the drug e.g. approval in another

country.