Ind Studies by Sejal Khuman

IND STUDIES
PREPARED BY : MS SEJAL.M.KHUMAN
M.PHARM 2ND SEM PHARMACOLOGY
SUBJECT : PTSM
GUIDE BY : Dr.PRAVIN.TIRGAR
CONTENT
1. Introduction of IND 9. Protocol amendments

(INVESTIGATIONAL NEW
10. Information amendments.
DRUG )
2. When we need IND and when we 11. IND safety reporting
don’t need IND 12. Annual reports.
3. Type of IND
13. Withdrawal of an IND
4. Resources for IND Applications
14. References
5. Requirement for an IND
6. Phases of an investigation. 15. Gtu questions
7. General principles of the IND

submission
8. IND content and format
2 Sejal Khuman 10/02/2021

1. INTRODUCTION
Definition
The Code of Federal Regulations (CFR) defines an investigational
new drug as:
"...a new drug or biological drug that is used in a clinical
investigation."
In the U.S. Food and Drug Administration (FDA) regulations, an
investigational new drug is any substance (such as a drug,
vaccine or other biological product) for which FDA approval is
being sought.
This may include a marketed product that is being used in a different
form than the one it was approved for, if a change is proposed in its
use, formulation, and route of administration.
Continue …….
 For new drugs and even most follow-on products (besides

generics), the results of certain nonclinical studies, known as IND-
enabling studies, must be submitted with the IND to support
investigational drug use in humans. IND-enabling studies help:
1) Predict potential safety concerns
2) Allow estimation of safe starting doses and dose ranges for

clinical trials
3) Identify key parameters for monitoring

2. WHEN WE NEED IND AND WHEN
WE DON’T NEED IND
When we need IND When we don’t need IND
• New drug or biologic product • Drugs and biologics
• New use of an approved • Study of placebo

drug or biologic
• Study of approved drug or
• New use of a combination of biologic used under the
an approved drugs or approved label
biologics
• Combination products in
which the components are
physically, chemically or
otherwise combined and the
primary mode of action is
due to the drug or biologic
3. TYPES OF IND
IND TYPES
NON
COMMERCIAL
COMMERCIAL
IND
IND
INVESTIGATOR EMERGENCY TREATMENT

IND IND IND

Continue….
(A)COMMERCIAL IND: Goal is to obtain marketing approval for a new

product.
(B) NON-COMMERCIAL IND : It includes :

1. INVESTIGATOR IND : In this case ,the physician is both the sponsor
and investigator.
2. EMERGENCY IND : FDA authorize immediate dispensing of a non-

approved drug in a life threatening situation when no standard
acceptable therapy is available.
3. 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.

The IND application must contain information in
three broad areas:
1. Animal Pharmacology and Toxicology Studies
2. Manufacturing Information
3. Clinical Protocols and Investigator Information

4. RESOURCES FOR IND APPLICATIONS
Pre-IND Consultation Program
I. Guidance Documents for INDs
II. Laws, Regulations, Policies and Procedures
III. Code of Federal Regulations (CFR)
IV. Manual of Policies and Procedures (MaPPs)
V. Emergency Use of an Investigational Drug or Biologic

Code of Federal Regulations
(CFR)
• The following regulations apply to the IND application process:
Number Regulation
21CFR Part 201 Drug Labeling
21CFR Part 54 Financial Disclosure by Clinical Investigators
21CFR Part 58 Good Lab Practice for Nonclinical Laboratory [A

nimal] Studies
21CFR Part 314 INDA and NDA Applications for FDA Approval to
Market a New Drug (New Drug Approval)
21CFR Part 56 Institutional Review Boards
21CFR Part 312 Investigational New Drug Application
21CFR Part 316 Orphan Drugs
21CFR Part 50 Protection of Human Subjects

5. REQUIREMENT FOR AN IND.
a) A sponsor shall submit an IND to FDA if the sponsor intends to conduct

a clinical investigation with an investigational new drug that is subject to
312.2(a).
b) A sponsor shall not begin a clinical investigation subject to 312.2(a) until

the investigation is subject to an IND which is in effect in accordance
with 312.40.
c) A sponsor shall submit a separate IND for any clinical

investigation involving an exception from informed consent Such
a clinical investigation is not permitted to proceed without the prior written
authorization from FDA. FDA shall provide a written determination 30
days after FDA receives the IND or earlier.

6. PHASES OF AN INVESTIGATION.
A. Phase 1.
 initial introduction of an investigational new drug into humans.
 conducted in patients or normal volunteer subjects
 designed to determine the metabolism and pharmacologic actions

of the drug in humans, the side effects associated with increasing
doses, and, if possible, to gain early evidence on effectiveness.
 The total number of subjects and patients included in Phase 1

studies varies with the drug, but is generally in the range of 20 to
80.

Continue……
B. Phase 2.
 Includes the controlled clinical studies conducted to evaluate the

effectiveness of the drug for a particular indication or indications in patients
with the disease .
 Determine the common short-term side effects and risks associated with the
drug.
 Conducted in a relatively small number of patients, usually involving no

more than several hundred subjects.
C. Phase 3.
 Expanded controlled and uncontrolled trials.
 Intended to gather the additional information about effectiveness and safety

that is needed to evaluate the overall benefit-risk relationship
 Phase 3 studies usually include from several hundred to several thousand

subjects.
7. GENERAL PRINCIPLES OF THE IND
SUBMISSION.
a) FDA's primary objectives in reviewing an IND are, in all phases of the
investigation, to assure the safety and rights of subjects, and, in phase 2
and 3, to help assure that the quality of the scientific evaluation of drugs
is adequate to permit an evaluation of the drug's effectiveness and
safety.
b) The amount of information on a particular drug that must be submitted in

an ind to assure the accomplishment of the objectives described in
paragraph (a).
 This section depends upon such factors as the novelty of the drug, the
extent to which it has been studied previously, the known or suspected
risks, and the developmental phase of the drug.
a) The central focus of the initial ind submission should be on the general

investigational plan and the protocols for specific human studies.
b)14 The ind format
Sejal Khuman
set forth in 312.23 should be followed routinely by 10/02/2021
sponsors in the interest of fostering an efficient review of applications
REVIEW OF INDA :

8. IND CONTENT AND FORMAT
A sponsor who intends to conduct a clinical investigation subject to this part shall submit

an “Investigational New Drug Application” (IND) including, in the following order:
1) Cover sheet (form FDA 1571)
2) Table of contents
3) Introductory statement & General investigational plan
4) Investigator’s Brochure
5) Protocols
6) Chemistry, Manufacturing & Control Information
7) Pharmacology and toxicology information
8) Previous Human Experience with the Investigational Drug
9) Additional Information
10) Relevant information.
(1) Cover sheet (Form FDA-1571)
A cover sheet for the application containing the following:
i. Name of drug
ii. Submission date
iii. Sponsor identification
iv. Phase of proposed clinical investigation
v. Sponsor commitments
vi. Identification of clinical monitor and safety evaluator
vii. Information regarding transfer of responsibilities to a contract research

organization.

(2) A table of contents

(3) Introductory statement and general investigational plan.

(4) Investigator's brochure
• If required under 312.55, a copy of the investigator's brochure, containing the
following information:
i. A brief description of the drug substance and the formulation, including the
structural formula, if known.
ii. A summary of the pharmacological and toxicological effects of the drug in

animals and, to the extent known, in humans.
iii. A summary of the pharmacokinetics and biological disposition of the drug in

animals and, if known, in humans.
iv. A summary of information relating to safety and effectiveness in humans

obtained from prior clinical studies. (Reprints of published articles on such
studies may be appended when useful.)
v. A description of possible risks and side effects to be anticipated on the basis

of prior experience with the drug under investigation or with related drugs,
and of precautions or special monitoring to be done as part of the
investigational use of the drug.
(5) Protocols.
• Clinical investigations are conducted according to protocols included in

the IND application
• New studies may begin when the sponsor has submitted the change to
FDA for its review and the new protocol or changes to the existing
protocol have been approved by the institutional review board (IRB) with
the responsibility for review and approval of the studies.

(6) Chemistry, manufacturing, and
control information.
Drug Substance:
Description of the Information regarding the :
• Physical ,Chemical or Biological characteristics of the drug substance, along
with the name and address of the manufacturer.
• General method of preparation
• identification of the analytical methods and
• acceptable limits used to assure the identity, purity and strength of the drug
substance.
 Drug Product:
• Information regarding the manufacturing facility,
• manufacturing and packaging procedure description,
• Identification of analytical methods,
• acceptable limits used to assure identity, purity, and strength of components
and finished products.
(7) Pharmacology and toxicology
information
• (i) Pharmacology and drug disposition.
• (ii) Toxicology.
(8) Previous human experience with

the investigational drug.
A summary of previous human experience known to the applicant, if any,

with the investigational drug

(9) Additional information
• (i) Drug dependence and abuse potential. If the drug is a psychotropic

substance or otherwise has abuse potential, a section describing relevant
clinical studies and experience and studies in test animals.
• (ii) Radioactive drugs. If the drug is a radioactive drug, sufficient data from

animal or human studies to allow a reasonable calculation of radiation-
absorbed dose to the whole body and critical organs upon administration to a
human subject. Phase 1 studies of radioactive drugs must include studies
which will obtain sufficient data for dosimetry calculations.
• (iii) Pediatric studies. Plans for assessing pediatric safety and

effectiveness.
• (iv) Other information. A brief statement of any other information that would

aid evaluation of the proposed clinical investigations with respect to their
safety or their design and potential as controlled clinical trials to support
marketing of the drug.
(10) Relevant information
a) Information previously submitted
b) Material in a foreign language
c) Number of copies
d) Numbering of IND submissions
e) Identification of exception from informed consent

9. PROTOCOL AMENDMENTS
Once an IND is in effect, a sponsor shall amend it as needed to

ensure that the clinical investigations are conducted according
to protocols included in the application
(a) New protocol.
(b) Changes in a protocol.
(c) New investigator.
(d) Content and format
(e) When submitted

10. INFORMATION AMENDMENTS
• Requirement for information amendment
• Content and format of an information amendment
• When submitted

11. IND SAFETY REPORTING
(a) Definitions
Adverse event
Life-threatening adverse event
Serious adverse event
Suspected adverse reaction
Unexpected adverse event
(b) Review of safety information

12. ANNUAL REPORTS
• A sponsor shall within 60 days of the anniversary date that the IND

went into effect, submit a brief report of the progress of the
investigation that includes
Individual study information
Summary information

13. WITHDRAWAL OF AN IND
a) At any time a sponsor may withdraw an effective IND without

prejudice.
b) If an IND is withdrawn, FDA shall be so notified, all clinical

investigations conducted under the IND shall be ended, all
current investigators notified, and all stocks of the drug returned
to the sponsor or otherwise disposed of at the request of the
sponsor in accordance with 312.59.
c) If an IND is withdrawn because of a safety reason, the sponsor

shall promptly so inform FDA, all participating investigators, and
all reviewing Institutional Review Boards, together with the
reasons for such withdrawal.

14. REFERENCES
1. https://www.fda.gov/drugs/types-applications/investigational-n
ew-drug-ind-application
2. https://www.law.cornell.edu/cfr/text/21/part-312/subpart-B
3. https://www.nuventra.com/resources/blog/ind-enabling-studie
s/

15. GTU QUESTIONS
1. Write about IND application form (W-2019)
2. Explain the type of IND. Write the details of IND application form .
(S-2018)(W-2018)


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IND STUDIES

1. Introduction of IND 9. Protocol amendments

7. General principles of the IND

2 Sejal Khuman 10/02/2021

 For new drugs and even most follow-on products (besides

1) Predict potential safety concerns

2) Allow estimation of safe starting doses and dose ranges for

3) Identify key parameters for monitoring

4 Sejal Khuman 10/02/2021

• New use of an approved • Study of placebo

INVESTIGATOR EMERGENCY TREATMENT

6 Sejal Khuman 10/02/2021

(A)COMMERCIAL IND: Goal is to obtain marketing approval for a new

(B) NON-COMMERCIAL IND : It includes :

2. EMERGENCY IND : FDA authorize immediate dispensing of a non-

3. TREATMENT IND : FDA will permit investigational drug to be used to

7 Sejal Khuman 10/02/2021

1. Animal Pharmacology and Toxicology Studies

3. Clinical Protocols and Investigator Information

8 Sejal Khuman 10/02/2021

Pre-IND Consultation Program

I. Guidance Documents for INDs

II. Laws, Regulations, Policies and Procedures

III. Code of Federal Regulations (CFR)

IV. Manual of Policies and Procedures (MaPPs)

V. Emergency Use of an Investigational Drug or Biologic

9 Sejal Khuman 10/02/2021

21CFR Part 54 Financial Disclosure by Clinical Investigators

21CFR Part 58 Good Lab Practice for Nonclinical Laboratory [A

21CFR Part 312 Investigational New Drug Application

21CFR Part 316 Orphan Drugs

21CFR Part 50 Protection of Human Subjects

10 Sejal Khuman 10/02/2021

a) A sponsor shall submit an IND to FDA if the sponsor intends to conduct

b) A sponsor shall not begin a clinical investigation subject to 312.2(a) until

c) A sponsor shall submit a separate IND for any clinical

11 Sejal Khuman 10/02/2021

 initial introduction of an investigational new drug into humans.

 conducted in patients or normal volunteer subjects

 designed to determine the metabolism and pharmacologic actions

 The total number of subjects and patients included in Phase 1

12 Sejal Khuman 10/02/2021

 Includes the controlled clinical studies conducted to evaluate the

 Conducted in a relatively small number of patients, usually involving no

 Expanded controlled and uncontrolled trials.

 Intended to gather the additional information about effectiveness and safety

 Phase 3 studies usually include from several hundred to several thousand

b) The amount of information on a particular drug that must be submitted in

a) The central focus of the initial ind submission should be on the general

15 Sejal Khuman 10/02/2021

A sponsor who intends to conduct a clinical investigation subject to this part shall submit

1) Cover sheet (form FDA 1571)

3) Introductory statement & General investigational plan

6) Chemistry, Manufacturing & Control Information

7) Pharmacology and toxicology information

8) Previous Human Experience with the Investigational Drug

A cover sheet for the application containing the following:

ii. Submission date