INVESTIGATIONAL NEW DRUG

• An Investigational New Drug (IND) refers to a pharmaceutical product that is

under investigation for its safety and efficacy in human clinical trials.
• It is a designation given by regulatory authorities, such as the U.S. Food and
Drug Administration (FDA), to a drug that has not yet been approved for
marketing.
• An investigational new drug (IND) application is an application that must be
submitted to the FDA to obtain permission to begin a clinical trial.
• An IND application is submitted by the clinical trial sponsor and must include
documentation of the pharmacology and toxicology studies demonstrating that
the compound has proven safe in animal testing.
• It will also contain manufacturing information, clinical protocols for the proposed
clinical trial, and information on the study investigators and staff. This report
must be submitted to the FDA before human testing may begin.

when we need IND study?

• An IND is required any time 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 under new dosage
form.
• Being administered at a new dosage form
• In combination with another drug and the combination is not approved
 When we do not need an IND?
An IND is not required to conduct a study if the drug:
• It is not intended for human subjects, but is intended for in vivo testing or lab
research animals (non clinical studies).
• It is an approved drug and study is within its approved indication for use.

IND APPLICATION PROCEDURE

When submitting IND applications, applicant have to send their applications in triplicate
(one original and 2 duplicate). Electronic submission should be considered whenever
possible.

Each application should be accompanied by

• Form 1571 (IND application cover)

• Form 1572 (investigators statement)

• Documentation containing chemistry, pharmacological, toxicological, medical,

microbiological, statistical data

• Upon receipt of an IND application, FDA will notify the sponsor of the date it receives
the application through an IND acknowledge letter.

• Then FDA review application for safety of drug for use in humans

• An IND application may go into effect 30 days after FDA receives the application,
unless FDA notifies the sponsor that the investigations described in the application are
subject to a Clinical Hold; or an earlier notification by FDA that the clinical investigations
in the IND begin.

• Once the IND application is an effect, a drug manufacture may ship the investigational
new drug to the investigator.

THE CONTENT AND FORMAT OF IND SUBMISSION

• Cover sheet/ covering letter-Form1571

• Investigator’s statement- Form 1572

• Documents

1 Table of contents

2 Introductory statement and general

3 Investigational plan

4 Investigator’s Broacher
 5 Protocols

6 Product information

7 Pharmacology/toxicology

8 Microbiological

9 Statistical data

10 Previous human experience

11 Additional information

COVER SHEET (FORM FDA 1571)

• Name, address, telephone no. of sponsor, date of application and name of new drug

• Identification of phases

• Commitment not to begin clinical investigations until IND approval

• Commitment by IRB- Form 56

• Commitment for conducting CT- accordance with regulations

• Name, title of person Monitoring the conduct

• Name, title – person(s) for reviewing the conduct

• Name, Address of CRO, if any

• Signature of sponsor

INTRODUCTORY STATEMENT

• Description of the investigational drug

• Details of the active ingredients

• Drug’s pharmacological classification

• Structural formula

• Route of administration

• Formulation of dosage form

• Objective

INVESTIGATIONAL PLAN

• Plan of study

• Duration of proposed clinical investigation.

• 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

INVESTIGATOR’S BROCHURE

• Structural formula of drug.

• Summary of pharmacological, toxicological, pharmacokinetic effects in

animals.

• Safety and efficacy in animals

• Purpose of study

• Dosage regimen [ Dose/Dosing frequency]

• Monitoring procedure

PROTOCOLS

A clinical protocol describes how a particular clinical trial is to be conducted

It includes:

▪ The objectives of study

▪ The study trial design

▪ How subjects are selected

▪ How the trial is to be carried out

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 where study will be carried out.

• Study subject inclusion and exclusion criteria.

• Estimate of the number of subjects to be enrolled in the study.

 PRODUCT CMC INFORMATION

• Describe drug substance

• Determines the methods used to manufacture the investigational drug

• Reagent and solvents

• Acceptable limits and analytical Quality control tests to ensure quality and purity of
drug

• Safety concerns

PHARMACOLOGY/TOXICOLOGY INFORMATION

• Non-clinical study summaries of pharmacological & toxicological effects

PREVIOUS HUMAN EXPERIENCE:

• Data from trials done at any part of the world

• Data from other INDs, NDAs

ADDITIONAL INFORMATION

• Other relevant information

• Summary of FDA meetings

• Copies of referenced materials

• Address issues on possible drug abuse, dependence, radioactivity and other safety
issues.

IND CATEGORIES
TYPES OF IND

➢ 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.

➢ Emergency Use IND allows the FDA to authorize use of an experimental drug in an
emergency situation that does not allow time for submission of an IND.

➢ Treatment IND 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.

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 is exhibit

pharmacological activity.

• It is important for the company to initiate and conduct the clinical studies of their new
product

• It secure safety and effectiveness of the clinical trial subjects

• It give the indication of the new drug.

• Pharmacology and toxicology information of new drug

INDUSTRY PERSPECTIVE
1Regulatory Compliance: Pharmaceutical companies need to ensure that their
studies meet the regulatory requirements set by the relevant authorities, such as the
Food and Drug Administration (FDA) in the United States.

2. Resource Optimization: Industries strive to optimize the allocation of resources,

including time, budget, and personnel, to efficiently conduct IND studies.

This involves planning and managing various aspects such as study timelines, patient
recruitment, data collection, and analysis

3 Commercial Viability: Pharmaceutical companies consider the potential market

value of the drug under investigation. They analyse factors like competitive landscape,
target population size, potential market demand, and pricing strategies to assess the
commercial viability of the drug.
 4.Risk-Benefit Assessment: Industries carefully evaluate the balance between the
risks and benefits associated with the investigational drug.

This includes assessing the potential efficacy, safety profile, and potential side effects
or adverse events to determine if the benefits outweigh the risks.

5.Intellectual Property Protection: Pharmaceutical companies aim to protect their

intellectual property rights during IND studies.

• This includes safeguarding proprietary information, patenting new discoveries, and

ensuring confidentiality

Market Differentiation: Industries may strategically design IND studies to differentiate

their products from existing therapies or competitors.

• This can involve conducting comparative effectiveness studies, exploring new

indications, or targeting specific patient populations.

List of 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 are any previous experience with the drug in humans (often foreign use).

2. Manufacturing Information –
➢ Information pertaining to the composition, manufacturer, stability, and controls used for
manufacturing the drug substance and the drug product.

➢ This information is assessed to ensure that the company can adequately produce and
supply consistent batches of the drug.

3. Clinical Protocols and Investigator Information –

➢ Detailed protocols for proposed clinical studies to assess whether the initial-phase
trials will expose subjects to unnecessary risks.

➢ Also, information on the qualifications of clinical investigators--professionals (generally

physicians) who oversee the administration of the experimental compound--to assess
whether they are qualified to fulfil their clinical trial duties.

Pharmacokinetics

➢ ADME

➢ Absorption
➢ Distribution

➢ Metabolism

➢ Excretion

P450 inhibition/induction

In vitro metabolism

Allometric scaling

Safety pharmacology

Layout chart for IND application