INVESTIGATIONAL NEW DRUG

APPLICATION- I N D A

Dr. Nithin Manohar R

M.Pharm, PhD, MSc Psychology,
Professor& HOD
Dept Of Pharmacy Practice
Pushpagiri College Of Pharmacy
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 CONTENT

 INTRODUCTION

 NEEDS

 CATEGORIES

 AREAS

 IMPORTANCE

 BASIC COMPONENTS

 UPDATION OF IND

 REVIEW

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 REFERENCE
 INTRODUCTION

Chemical that has not undergone clinical testing

investigational new drug.

An IND application is a submission to the respective

government authority ( FDA ) requesting permission to
start clinical study of a new drug product.

If IND is approved , it is an evidence of safety & efficacy

for proposed human studies.

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 An IND is required whenever a sponsor wants to
conduct a clinical trial of an unapproved drug.

IND also required in cases where composition of

the drug is such that the drug is not recognized as
safe & effective in prescribed , suggested or
recommended the conditions on label.

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 The need of I n d for studies

1. For new chemical entity.

2. For a drug not approved for the indication

under investigation.

3. For a new dosage form.

4. For a new combination to be approved.

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 CATEGORIES OF IND

Investigational
New Drug
Application

NON-
COMMERCIAL
COMMERCIAL

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 Commercial:
Commercial INDs are applications that are
submitted by companies .

whose ultimate goal is to obtain marketing approval

for a new drug.

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 Non commercial:
These mainly includes;

1. Investigator IND

2. Emergency use IND

3. Treatment IND

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 1. Investigator IND
 It is submitted by a physician.

 The physician who both initiates & conducts an

investigation.

 Under whose immediate direction the

investigational drug is administered or dispensed.

 A physician might submit a research IND to

propose studying an unapproved drug or an
approved product for a new indication or in a
new patient population.
9  Sponsor and investigator
 2.Emergency use IND
 It allows the FDA to authorize use of an
experimental drug in an emergency situation that
does not allow time for submission of an IND in
accordance to the regulations.

 It is also used for patients who do not meet the

criteria of an existing study protocol , or if an
approved study protocol does not exist.

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 3. Treatment IND

It is submitted for experimental drugs

showing promise in clinical testing for serious or
immediately conditions while the final clinical
work is conducted & the FDA review takes place.

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 The IND application must contain
information in 3 broad areas;

1. Animal Pharmacology & toxicology studies.

2. Manufacturing information

3. Clinical protocols & investigator information

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 1.Animal pharmacology & toxicology studies

 Preclinical data to permit an assessment as

to whether the product is reasonably safe for
initial testing in human.

 Also included any previous experiences

with the drug in humans ( often of foreign origin ).

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 2. Manufacturing information

 Information pertaining to the composition,

manufacture, stability , & controls used for
manufacturing the drug substance & the drug
product.

 This information is assessed to ensure that

the company can adequately produce & supply
consistent batches of the drug.

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 3. Clinical protocols & investigator information

 Detailed protocols for proposed clinical studies mainly

used to assess whether the initial- phase trials will expose
subjects to unnecessary risks.

 Also , information on the qualifications of clinical

investigators ( generally physician ) who oversee the
administration of the experimental compound, to assess
whether they are qualified to fulfill their clinical trial duties.

 Finally , commitments to obtain informed consent from

the research subjects, to obtain review of the study by an IRB &
15 to adhere to the IND regulations.
 Before conducting clinical studies , the investigator
or sponsor should consult the staff of their regulatory
dept & if required may consult the IRB.

 The IRB is formally designated by an institution to

review & approve the initiation or research involving
human subjects with the primary intention of protecting
rights as well as welfare of human subjects.

 A meeting b/w a sponsor & statutory agency (FDA)

can be very useful to aid solutions of scientific &
technical problems with the help of available resources.

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 Importance of IND
1. Discloses knowledge about the manufacturing ,
pharmacology , & toxicology of the drug to support
its use in human testing.

2. Requires that the clinical investigations be

performed in accordance with good clinical
practice ( GCP).

3. Provides an additional level of protection through

FDA oversight.

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 BASIC COMPONENTS OF IND

1) Detailed cover sheet

2) Table of contents
3) An introductory statement
4) Basic investigational plan
5) Investigator’s brochure
6) Detailed investigation protocols.
7) Actual & proposed chemistry of compound.
8) Pharmacological & toxicological information on the compound.
9) Details of previous human experience with compound ( if any )
10) Any other information asked by FDA.
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 Cover sheet
It provides details of the investigational
new drug application & includes basic information
like ,
 Name of sponsor
 Investigational new drug number.
 Name of drug
 Type of submission
 Serial number
 Content of application.

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 COMMITMENT OF SPONSOR

1 . The sponsor should not initiate clinical study until 30 days

after the FDA receives the IND.

2. The sponsor should not start clinical study if so notified by

the FDA or when placed on clinical hold.

3. The sponsor shall ensure that IRB grants the initial

approval of each study & undertakes to perform periodic
reviews of the studies.

4. The sponsor should conduct the investigation in

accordance with all other applicable regulatory
requirements.
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  Content of IND

 introductory statement;

 this provide an overview of the investigational

drug & the plan of investigation.

 It should begin with a description of the drug & the

indications to be studied, followed by structure,
pharmacological class , dosage form , route of
administration etc

 Protocol of the clinical study

 Protocol gives all the information regarding the

conduct of the proposed clinical study including,
21 objectives, trial design, selection of subjects etc.
  Investigator’s brochure

 Minimum required information in investigator’s brochure;

1. Physical, chemical, & pharmaceutical properties of the drug.

2. Supply, storage, & handling information on the drug.

3. Chemical name & chemical structure of the drug.

4. Summarized relevant information about non- clinical

pharmacology.

5. Summary of safety & efficacy profile of the drug.

6. Guidelines regarding management of subject participating in

the trial.
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 Essential content of the protocol

1. Name , address & qualification of each investigator & co- investigator.

2. Name & address of each clinical site.

3. Name & address of each institutional review broad.

4. Copies of each report form.

5. Inclusion & exclusion criteria of subjects.

6. Estimate of the number of subjects to be enrolled.

7. Study design, methods employed to minimize bias on the part of subjects & investigators.

8. Maximum proposed dose & duration of exposure of the subjects.

9. Methods of measurement & observations to be made.

10. Clinical procedure & laboratory tests planned to monitor the effects of drug in the subjects.
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11. Methods to be used to determine the doses to be administered.
 Updation of the IND

 Clinical development of drug is a long term process

which usually takes 10- 12 years .

 It is necessary to update the investigational new drug

application.

 The updation continuously may be in the form of new

information or new protocols as the drug moves from
one phase to another.

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 THE VARIOUS COMMON TYPES OF AMENDMENTS & REPORTS ARE ;

1. The IND safety report

The sponsor of IND shall continuously review the safety of IDs

obtained from various sources like,

 Preclinical studies
 Clinical investigations
 Scientific journals
 Marketing feed backs etc

 The regulations discuss 2 types of safety reports;

1. 15 day report – it is a report of serious & unexpected events with the use of ID
that should be submitted to FDA in the prescribed form within 15 days of their
occurrence.

2. 7 day report – it is more urgent report where in serious & unexpected events are
25 noted with the use of a drug. In this case it is mandatory to inform to the FDA
by telephone followed by submission within the 7 calendar days.
 2. Protocol amendments

 A protocol amendment is submitted to initiate a new

clinical study that is either not described in the existing
IND or if the sponsor has made some changes to the
original IND.

 A protocol amendment includes copy of new protocol &

brief summary of difference b/w old & new protocol.

3. Information amendment

 This is the process of submission of important information to

the IND that is not with the scope of a protocol amendment.

 This may consist of information related toxicology,

pharmacology, chemistry manufacturing, discontinuation of
clinical study etc
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 Review of IND application
As per GCP guidelines ,FDA conducts review of the
IND application with the focus on

 safety for human research subjects &

 ensuring that the studies will produce useful

information to assess safety & efficacy of the test
product.

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  The reviews are conducted by a team of experts which
includes

1. Medical officer

2. Consumer safety officer / project manager

3. Statistician

4. Chemist

5. Pharmacologist

6. Human bio pharmaceutics expert

28 7. microbiologist
 once IND is submitted, the sponsor must wait 30
calendar days before initiating any clinical trials.
During this time , FDA has an opportunity to
review the IND for safety ,to assure that research
subjects will not be subjected to any unreasonable
risk.

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 APPLICANT ( DRUG SPONSOR)

IND

REVIEW BY CDER

MEDICAL CHEMISTRY PHARMACOLO STATISTICAL

GY &
TOXICOLOGY
SAFETY REVIEW SPONSOR SUBMITS NEW DATA

SAFETY ACCEPTABLE FOR COMPLETE THE

STUDY TO PROCEEDS ? REVIEW

REVIEW
ACCEPTABLE

30 STUDY ON GOING*
 Reference
Essentials of clinical research by Dr. Ravindra B
Ghooi, Sachin C Itkar, page no. 15.1- 15.10

Drug regulatory affairs ( clinical trials) for

professional diploma in clinical research , module 3 ,
page no. 4- 6.

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 THANK YOU

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