INVESTIGATIONAL NEW DRUG APPLICATION (IND)

Objective
Definition
Types
Review

1. S.GOKULAKRISHNAN
M.Pharm (Pharmaceutics) – I Year,
Mother Theresa Post Graduate and Research Institute of
Health Sciences,
(A Government of Puducherry Institution)
Puducherry.
NON CLINICAL DRUG DEVELOPMENT
GOKULAKRISHNAN NON CLINICAL DRUG DEVELOPMENT 1

2. NON CLINICAL DRUG DEVELOPMENT
In drug development, preclinical development, also
named preclinical studies and nonclinical studies, is a stage of
research that begins before clinical trials (testing in humans) can
begin, and during which important feasibility, iterative testing and
drug safety data are collected.

The main goals of pre-clinical studies are to determine the safe
dose for first-in-man study and assess a product's safety profile.
Products may include new medical devices, drugs, gene therapy
solutions and diagnostic tools.

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3. DRUG DEVELOPMENT

Development of a new therapeutic
drug is a complex, lengthy and
expensive process.


costs nearly huge amount
and an average of 15 years.

.
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4. NON CLINICAL DRUG DEVELOPMENT
GLOBAL SUBMISSION OF
1. INVESTIGATIONAL NEW DRUG APPLICATION (IND)
2.NEW DRUG APPLICATION (NDA)
3.ABBREVIATED NEW DRUG APPLICATION (ANDA)
INVESTICATION OF MEDICINAL PRODUCTS DOSSIER
(IMPD)
INVESTIGATOR BROCHURE

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5. INVESTIGATIONAL NEW DRUG APPLICATION
(IND)
OBJECTIVES
To assure the safety and rights of subjects in all phases of an
investigation.

In phases 2 and 3, to help assure that the quality of the
scientific evaluation of the drug according to the -- (21 CFR
312.22).

Code of Federal Regulations, part 312 (21 CFR
part 312) (the IND regulations).



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6. 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.
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7. 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.

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8. 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.

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

All clinical studies where a new drug is
administered to human subjects , regardless of
whether the drug will be commercially
developed,require an IND.
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10. 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.

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11. 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.


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12. 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 1
st proposed
human study.
To assure that the human subjects who participate in the
proposed study will not be exposed to unreasonable and
significant risk.


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13. GOKULAKRISHNAN NON CLINICAL DRUG DEVELOPMENT 13

14. 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)

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15. CONTENT AND FORMAT OF AN IND APPLICATION
(Cont..)
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)


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16. 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.
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17. FDA FORM 1571 (Cont..)
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).

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18. 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.

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19. 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
14. Name and title of the person responsible for review and
evaluation of information relevant to the safety of drug
15. Name of sponsor’s authorized representative
16.Signature
17.Address
18.Telephone no.
19.Date

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20. 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.

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21. 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

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22. 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

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23. 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

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24. CLINICAL PROTOCOL(Cont..)
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.

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25. 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.
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26. PHARMACOLOGICAL AND TOXICOLOGICAL
DATA
Pharmacology and drug disposition
Integrated toxicology summary
Previous human exposure :
Marketed (foreign) or previously tested in humans.

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27. 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
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28. FDA REVIEW OF THE IND
(Cont..)
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.

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29. 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.

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30. Applicant\Drug Sponsor
IND
Review by CDER
Medicinal chemistry Pharmacological \ Toxicological statistical
Safety Review Sponsor submits new data
Safety acceptable for
Chemical hold decision No Safety acceptable for
study to proceed
Chemical hold decision
Complete reviews Notify Sponsor
Review complete & acceptable? Sponsor notified of deficiencies
No Deficiencies
Study ongoing
No
No
No
Yes
Yes
Yes
Investigational New Drug Application (IND)

31. 10
Investigational New Drug Application (IND) in INDIA

32. REFERENCES
21 CFR.org
 www.Wikipedia.org
www.Cdsco.com
Drug regulatory affairs by thimasetty. Drug regulatory affairs by thimasetty.
19
http://www.medicalnewstoday.com/
artes/172522.php

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