Investigational new drug

1. Presented by
Mr. Sunil Balasaheb Sitaphale
Roll number:- 15
Department of Pharmacology
IPER Wardha
IND Enabling Studies
A Seminar presentation on topic
INSTITUTE OF PHARMACEUTICAL EDUCATION AND
RESEARCH, WARDHA
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CONTENTS
Definition of IND
Importance of IND
Industry perspective
Studies needed for IND submission
Safety pharmacology studies- Objective
HERG Assay
Reference

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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 on humans.
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 products.
The IND application provides the FDA with the data necessary to decide whether the new drug the
proposed clinical trial pose a reasonable risk to the human subjects participating in the study.

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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.

5. TYPES OF IND STUDIES
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All clinical studies where a new drug is administered to human subjects, regardless of whether the drug
will be commercially developed ,require an IND.
1. Investigator IND is submitted by a physician who both initiates and conducts an investigation,
and under whose immediate direction the investigational drug is administered or dispensed.
2. Emergency IND All the FDA to authorize use of an experimental drug in an emergency
situation.
3. Treatment IND is submitted for experimental drugs showing promise in clinical testing
serious or immediately life-threatening conditions while the final clinical work is conducted
and the FDA review takes place.

6. Classification of IND
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Commercial: permits sponsor to collect data on clinical safety and effectiveness needed for
application for marketing in the form of NDA.
Research (non-commercial) : permits the sponsor to use drug in research to obtain advanced
scientific knowledge of new drug o no plan to market the product.

7. IMPORTANCE OF IND
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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 in assuring the marketing of a new drug and responsibility for compliance of sponsor.
It is important for the company to initiate and conduct the clinical studies of their new product.
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 indication of new drugs.
Pharmacology and toxicology information of new drugs.

8. Studies needed for IND submission
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The IND application must contain information in three broad areas: 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 are any previous experience with the drug in
humans (often foreign use).
Application content: The IND application must contain information in three broad areas:
• 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 are any previous
experience with the drug in humans (often foreign use).

9. Classification of Retroviral Drugs
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Chemistry and manufacturing information studies - information pertaining to
is chemical composition, manufacturing methods, 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.
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).

10. IND (Investigational New Drug Application)
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An investigation new drug application (IND) is a submission to food & drug administration
(FDA) requesting permission to initiate the study of new drug product
FDAs role in the development of a new drug begins when the drug's sponsor has screened the
new molecule for pharmacological activity and acute toxicity potential in animals, wants to
test its diagnostic or therapeutic potential in humans.
The molecule changes in legal status under the federal food, drug, and cosmetic act and
becomes a new drug subject to specific requirements of the drug regulatory system.
Drug is to be the subjected to an approved marketing application before it is transported
distributed across state lines.
IND- notice of claimed investigational exemption for a new drug must be filed with
regulatory body

11. REQUIREMENTS FOR IND
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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.
Phases Of Investigation
Phase 1 - ADME (20- 80) healthy subjects
Phase 2 - effectiveness in particular indication (several hundred patients)
Phase 3 - safety and effectiveness (100-1000) subjects.
General Principle Of IND
To assure safety and rights of the subject.
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 & protocol which should be supported
by additional information
Including animal toxicological studies

12. IND CONTENT & FORMAT
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1. Cover sheet (FORM FDA 1571)
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.

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2.TABLE OF CONTENTS
Comprehensive listing of contents of IND application broken in volumes & page number.
Toc should include details of sections, appendices, attachments, reports & other reference material
A well drafted TOC will facilitate the task of review & decrease the review time.
3. GENERAL INVESTIGATIONAL PLAN –
A brief 3 to 4 pages note on - the investigational product
Sponsors 'investigational plan
Goal of the section is to -
To provide brief description of the drug
Layout development plan of the drug

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4. INVESTIGATORS BROCHURE
Key document provided to each investigator & IRB at each of the clinical site.
Includes
1. All about the investigational drug
2. IB is a living document & must be updated by the sponsor.
5.PROTOCOLS
Describes how the clinical trial would be conducted.
It describes -
the objective of the study
The trial design
How subjects would be selected?
How the trail is to be conducted?
All about the how the study would be conducted?

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6. CHEMISTRY, MANUFACTURING AND CONTROL INFORMATION
CMC information Sufficient detail on QUALITY, IDE
NITY, PURITY & 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

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7. PHARMACOLOGY AND TOXICOLOGY INFORMATION
Pharmacology & toxicology data.
Non-clinical safety data that sponsor generated to prove that the IP is safe for clinical study.
The amount & type of data depends on class of 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.

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IND APPLICATION PROCESS
EARLY CONSULTATION
Sponsors may request to meet with FDA reviewing
Officials early in the drug development process to review and reach agreement on the design of necessary
preclinical and clinical studies.
Pre-investigational new drug (IND) meetings:
Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing
officials.
The primary purpose of this meeting is to review and reach agreement on the design of animal studies
needed to initiate human testing.
The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans
for studying the drug product in pediatric populations, and the best approach for presentation and
formatting of data in the IND

18. SAFETY PHARMOCOLOGY STUDIES
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Safety pharmacology is an essential part of the drug development process that aims to identify and
predict adverse effects prior to clinical trials. SP studies are described in the international conference
on harmonization (ICH) s7a and s7b guidelines.
The supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated
therapeutic and supra-therapeutic exposures on major organ systems. This outlines the current practices
and use of non-standard species, biomarkers, and combining toxicology. The core battery SP studies,
performed according to good laboratory practice (GLP) standards as per the ich guidelines, involves
the investigation of the major vital organ systems including :-
Cardiovascular system (CVS)
Central nervous system (CNS)
Respiratory system
Renal system
Gastrointestinal system

19. ОВJЕСTIVE OF SAFETY PHARMACOLOGY
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According to ICH S7А:-
To identify undesirable pharmacodynamic properties of a substances.
To evaluate adverse pharmacodynamic and pathophysiological effect of a substance.
To investigate the mechanism of action of a adverse pharmacodynamic effect.

20. HERG ASSAY
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(HUMAN ETHER RELATED GENE)
The alpha subunit of a potassium ion channels in the heart that codes for a protein known as k,11.1
Ion channel proteins (the 'rapid' delayed rectifier current (i)) that conducts potassium (K+)
ions out of the muscle cells of the heart
Inhibition of the herg current causes QT interval prolongation resulting in potentially fatal
ventricular tachyarrhythmia called torsade de pointes.

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22. Reference
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