Investigational New Drug Application enabling studies.pptx

IND Enabling Studies
Nikita bankoti
M.Pharm 2nd sem.
Pharmacology

Definition Of IND:
An IND (investigational new drug application) is a submission to
food and Drug Administration (FDA) requesting permission to
initiate the study of new drug product on human.
In many ways, the investigational new drug (IND) application is the
result of a successful preclinical development program.
The IND is also the vehicle through which a sponsor advances to the
next stage of drug development known as clinical trials(human trials).

During a new drug’s early preclinical development, the sponsor’s
primary goal is to determine if the product is reasonably safe for
initial use in humans, and if the compound exhibits pharmacological
activity that justify commercial development.
When a product is identified as a viable candidate for further
development, the sponsor then focuses on collecting the data and
information necessary to establish that the product will not expose
humans to unreasonable risks when used in limited, early-stage
clinical studies.

An investigational new drug (IND) application is to provide the data
showing that it is reasonable to begin tests of a new drug on human.
FDA’s role in the development of a new drug begins when the drug’s
sponsor (usually the manufacturer or potential marketer), having
screened the new molecule for pharmacological activity and acute
toxicity potential in animals, wants to test its diagnostic or therapeutic
potential in human.

Drug-discovery And Approval Process:

Two stages of new drug approval for
human use:
Research prior to “approval”
- Requires research permit: e.g., Investigational New Drug
Application (IND)
Marketing after “approval”
- Requires marketing permit: e.g, New Drug Application (NDA)

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 trial 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.

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.

Who can apply for IND?
APPLICANT (Drug sponsor)
An applicant, drug sponsor is the person or entity who assumes
responsibility for the marketing of a new drug, including
responsibility for compliance with applicable provisions of the
Federal Food, Drug, and Cosmetic Act and related regulations.
The “sponsor” is usually an individual, partnership, corporation,
government agency, manufacturer or scientific institution.

The IND application provides FDA with data necessary to decide
whether the new drug and the proposed clinical trial pose a
reasonable risk to human subjects participating in the study.
The IND application allows the company to initiate and conduct the
clinical studies of their new drug product.
The safety of the clinical trial subjects is always the primary concern
of FDA

Classification of IND:
COMMERCIAL
- Permits sponsor to collect data on clinical safety and effectiveness
needed for application for marketing in the form of IND.
RESEARCH (non- commercial)
- Permits the sponsor to use drug in research to obtain advanced
scientific knowledge of new drug, No plan to market the product.

Type’s of IND Applications:
1. Investigator IND application
2. Emergency use IND application
3. Treatment IND application
4. Screening IND application

1. Investigator IND Application
Application is submitted by a physician, who both initiates and
conducts an investigation, under whose immediate direction the
investigational drug is administered or dispensed.
A physician might submit a research IND application to propose
studying of;
An unapproved drug
An approved product for a new indication
An approved product in a new patient population or new dosage level

2. Emergency use IND Application
Application allows the FDA to authorize use of an experimental drug
in an emergency situation that does not allow time for submission of
an IND application, in accordance with 21CFR, Sec.321.23 or Sec
312.20
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.
In such a case, FDA may authorize shipment of the drug for a
specified use in advance of submission of an IND application.

3. Treatment IND application
Application is submitted for experimental drugs showing promise in
clinical testing for serious or immediately life-threatening conditions
while the final clinical work is conducted and the FDA review takes
place.
A drug that is not approved for marketing, may be under clinical
investigation for a serious or immediately life-threatening disease
condition in patients for whom no comparable or satisfactory
alternative drug or other therapy is available.

4. Screening IND Application
Filed for multiple, closely related compounds in order to screen for
the preferred compounds or formulations.
The preferred compound can then be developed under a separate
IND
Used for screening different salts, esters and other drug derivatives
that are chemically different, but pharmacodynamically similar

Importance of IND:
Helps in the result of successful preclinical development program.
IND is also the vehicle through which a sponsor advice the next
stage of drug development i.e. clinical trial.
The preclinical study, helps the sponsor’s primary goal to determine
that the product is reasonably safe for initial use in human.
It is important in the commercial development of compounds if it
exhibit pharmacological activity.
It is important for the company to initiate and conduct the clinical
studies of their new product.

It is important in assuring the marketing of a new drug and
responsibility for compliance of sponsor.
It secure the safety and effectiveness of the clinical trial subjects.
IND can be alternative in a life threatening situation when no
standard acceptable therapy is available.
It gives the pharmacology and toxicology information of new drugs.

Studies Needed For IND Submission:
The IND application must contain information in three broad areas:
1. Animal Pharmacology and Toxicology studies.
-Preclinical data to permit an assessment as to whether the product is
reasonably safe for initial testing in humans. Also included any previous
experience with the drug in human(often foreign use).
2. Chemistry and manufacturing Information studies.
-Information pertaining to the chemical composition, manufacturing
method, stability and controls used for manufacturing the drug substance
and the drug product. The chemical stability and activity of the product
must also have been tested. This information is assessed to ensure that the
company can adequately produce and supply consistent and active batches
of the drug.

3. Clinical Protocols and Investigator Information studies.
-Detailed protocols for proposed clinical studies to assess whether the
initial-phase trials will expose the subjects to unnecessary risks.
Information on the qualifications of clinical investigators-
professionals (generally physicians).
Also, information on the qualifications of clinical investigators who
oversee the administration of the experimental compound to assess
whether they are qualified to fulfil their clinical trials duties.

As per 21CFR part 312:
The content and format of IND application is laid out in 21CFR(code
of federal regulation) 312.

Subpart B: IND Application
312.20 REQUIREMENT OF AN IND
- A sponsor shall submit an IND to FDA who intends to conduct a clinical
investigation.
- Investigation is not supposed to begin without prior written authorization
of FDA.
312.21 PHASES OF INVESTIGATION
PHASE1- ADME (80-100) healthy subjects.
PHASE2- effectiveness in particular indication (several 100-500 patients).
PHASE3- safety and effectiveness (1000-5000) subjects.

312.22 GENERAL PRINCIPLE OF IND
-To assure safety and rights of the subjects
-To assure the scientific quality of investigation will yield data
capable of meeting statutory standards for marketing approval.
-The central focus should be on general investigational plan and
protocol which should be supported by additional information
including animal toxicological studies.

312.23 IND Content and Format:
1. Cover sheet (FORM FDA 1571,1572)
2. Table of contents
3. Introductory statement and a general investigational plan
4.Investigators brochure
5. Protocols
6. Chemistry, manufacturing and control information
7. Pharmacology and Toxicology information
8. Previous human experience with the investigational drug
9. other relevant information like no. of IND submissions, no. of copies to be submitted(1+2)
10. protocol amendments, any changes in the protocol

1.FORM’s
FORM 1571: Sponsor files the IND application in form 1571 to the
FDA for review once successful series of preclinical studies are
completed.
FORM 1572: Along with the IND application, the sponsor submits
the statement of the Investigator (Investigator’s undertaking) in form
1572.

Investigational New Drug Application enabling studies.pptx

2. Table of contents
Comprehensive listing of contents of IND application broken in
volumes and page number.
TOC should include details of:
-sections, appendices, attachments, reports and other reference
material.
A well drafted TOC will facilitate the task of review and decrease the
review time.

3. General Investigational Plan
A brief 3 to 4 pages note on-
- the investigational product
- sponsor’s investigational plan
Goal of the section is to-
- to provide brief description of the drug
- layout development plan of the drug

4. Investigators brochure
Key documents provided to each investigator and IRB(Institutional
Review Board) at each of the clinical site.
It includes-
- all about the investigational drug.
- IB is a living document and must be updated by the sponsor.

5. Protocols
It describes how the clinical trial would be conducted.
- The objective of the study
- The trial design
- How subjects would be selected?
- How the trial is to be conducted?
- All about how the study would be conducted?

6. Chemistry, manufacturing and
control information
CMC information-
-Sufficient detail on QUALITY, IDENITY, PURITY and POTENCY of the drug
product.
-manufactured in conformance with cGMP.
CMC section includes the following-
1. Introduction CMC
2. Summary
3. Information of Placebo, if any
4.Proposed clinical label
5. Categorical exclusion of any environmental assessment

7. Pharmacology and Toxicology
information
Pharmacology and Toxicology data
Non-clinical safety data that sponsor generated to prove that the IP is
safe for clinical study.
The amount and type of data depends on class on new drug
Duration of proposed clinical trial patient population that will be
exposed during the trial

8. Previous human experience with the
investigational drug
- Integrated summary report of any human studies conducted on the
investigational drug
- Relevant to the safety of the investigations to be done- PK studies,
PD studies
- Observed adverse event profile

9. Other relevant information
No. of copies to be submitted (1+2) i.e. one original and 2 additional
copies of each application.
Additional information: special topics like Drug dependence, radioactive
drugs, abuse potential.
Other relevant information-
-Financial disclosure information from each investigator and sub
investigator.
-Drug master file(DMF).
-Reports or journal articles.

IND Review process
Once the IND application is submitted, the sponsor must wait 30
calender days before initiating any clinical trials.
If the sponsor hears nothing from CDER (center for drug evaluation
and research), then on Day 31 after submission of IND application,
the study may proceed as submitted.
The CDER is a division of the FDA that review INDA to ensure that
the drug are safe and effective

Investigational New Drug Application enabling studies.pptx

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