INVESTIGATIONAL NEW DRUGS APPLICATION (IND) STUDIES (PART II)
Presented by:
Manashi Karmakar
ADTU/0/2024-26/MPLS/011
M.Pharm, 2nd Semester
Faculty of Pharmaceutical Science
Assam down town University
Shankar Madhab Path, Gandhinagar,
Panikhaiti, Guwahati-781026,
Assam
CONTENTS
• Investigational New Drug Application
• Requirements for IND
• Studies Needed For IND Submission
• IND Contents and Formats
• IND Application Process
• FDA’s IND Review Process
IND (Investigational New Drug Application):
An investigation new drug application (IND) is a submission to food & drug administration (FDA) requesting
permission to initiate the study of new drug product.
FDA's role in the development of a new drug begins when the drug's sponsor has screen new molecule for
pharmacological activity and acute toxicity potential in animals, wants its diagnostic or therapeutic potential in
humans.
The molecule changes its 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 or distributed across state lines.
IND- notice of claimed investigational exemption for a new drug
must be filed with regulatory body.
REQUIREMENTS FOR 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.
Phases Of Investigation
• Phase 2- efficacy and • Phase 3- safety and
• Phase 1-ADME (20-
side effects (several effectiveness (100-1000)
80) healthy subjects
hundred patients) subjects.
• Safety and • Scientific
rights of the evaluation
subject.
General Principle
of IND
• Regulatory • Animal
Compliance toxicological
studies
STUDIES NEEDED FOR IND SUBMISSION:
Application content: The IND application must contain information in three broad
areas:
preclinical data to permit an assessment as to whether the
1. Animal pharmacology and
product is reasonably safe for initial testing in humans.
toxicology studies -
• chemical composition, manufacturing methods, stability,
and controls used for manufacturing the drug substance
and the drug product.
2. Chemistry and manufacturing • The chemical stability and activity of the product must
information studies - 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.
Detailed protocols for proposed clinical
3. Clinical Protocols and studies to assess whether the initial-phase
Investigator Information studies - trials will expose the subjects to unnecessary
risks.
IND CONTENTS AND FORMAT:
1. Tables of Contents
2. General Investigational Plan 3. Investigators Brochure
Should includes –
• Details of section • Sponsors investigational plan • Includes all about the
• Appendices • Provide brief description of investigational drugs
• Attachments drugs • It is a living documents &
• Reports • Layout development plan of must be updated by sponsors.
• It should decrease the the drug
review time
4. Protocols
5. Chemistry, manufacturing
Describes: and control information
• how clinical trials are conducted
• Objective of the study Includes information:
8. Other Relevant Information
• trial design • Quality, Purity & Potency of
• How subjects would be selected? the drug product
• Information specifically
• How the trial is to be conducted? • Manufacture in conformance
requested by FDA
with cGMP
• Financial disclosure
information from each
investigator and sub
investigator
6. Pharmacological & Toxicological • Drug master file (DMF)
Information 7. Previous Human Experience • Reports or journal articles
With The Investigational Drug • IND application is always
Includes: submitted in 1+2 format i.e. 1
• Pharmacological & Toxicological • Summary report of any human original & 2 additional copies
data studies conducted on of each application
• Amount & type of data depends investigational drug
on class of new drugs • Observed adverse events profile
• Duration of proposed clinical trial
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 submission of the initial IND, the sponsor may request a meeting with FDA-review officials
It is to review and reach agreement on the design of animal study needed to initiate human testing
Furter to discuss the scope and design of phase 1 testing, plans for studying the drug product in pediatric
populations, and the best approach for presentation formatting of data in the IND
END-OF-PHASE 1 MEETINGS:
Purpose of meeting is to review and reach agreement on the
design of phase 2 control clinical trials, with the goal that such
When data from phase 1 clinical testing testing will be adequate to provide sufficient data on the drug's
are available, the sponsor may again effectiveness to support a decision on its approvability for
request a meeting reviewing officials. marketing, and to discuss and timing of the drug in pediatric,
as well as the design patients.
END OF PHASE 2 MEETINGS:
It is further
Is to determine the safety of Once the IND is stamped
categorically divided
proceedings to phase-3 as received, it is sent to
into different sections-
CDER for review.
• Medical
• Chemistry
• Pharmacology/toxicology
• Statistics
FDA’s IND REVIEW PROCESS:
1. SAFETY REVIEW:
Following review of an initial IND If the sponsor hears nothing from CDER, then
submission, CDER has 30 calendar days to on day 31 after submission of the IND, the
decide if a clinical hold is necessary. study may proceed as submitted.
2. CLINICAL HOLD DECISION:
A clinical hold is the mechanism that CDER
uses when it does not believe, or cannot If this occurs, the center will contact the
confirm, that the study can be conducted sponsor within the 30-day initial review period to
without unreasonable risk to the stop the clinical trial.
subjects/patients.
CDER may either delay the start of an
early-phase trial on the basis of information
submitted in the IND, or stop an ongoing When a clinical hold is issued, a sponsor must
study based on a review of newly submitted address the issue that is the basis of the hold
clinical protocols, safety reports, protocol before the order is removed
amendments, or other information.
Clinical hold
A clinical hold can be –
“Complete clinical hold” - a delay or suspension of all clinical work requested under IND
submission
“Partial clinical hold”- a delay or suspension of only part of clinical work e.g. Part of protocol
3. NOTIFY SPONSOR:
Once a clinical hold is placed on a commercial
The division is required to send a letter within
IND, the sponsor will be notified immediately by
five working days following the telephone call.
telephone by the division director.
The sponsor may then respond to CDER by sending
an "IND clinical hold response" letter to the division. The letter should describe the reasons for the
To expedite processing, the letter must be clearly clinical hold, and must bear the signature of the
identified as an "IND CLINICAL HOLD RESPONSE" division director (or acting division director).
letter.
If the division does not reply to the clinical hold
response within 30 calendar days, the division
The division then reviews the sponsor's response director will telephone the sponsor and discuss
and decides within 30 days as to whether the hold what is being done to facilitate completion of the
should be lifted. review.
If it is decided that the hold will not be lifted, the The office director must decide within 14
hold decision is automatically sent to the office calendar days whether or not to sustain the
director for review. division's decision to maintain the clinical hold.
The letter will be sent within 5 working days of If the decision is made to lift the hold, the
the telephone call. However, the trial may begin division telephones the sponsor, informs
once the decision has been relayed to the sponsor by them of the decision, and sends a letter
telephone. confirming that the hold has been lifted.
4. SPONSOR NOTIFIED OF DEFICIENCIES:
In either case, the division
If other deficiencies are
informs the sponsor that it may
found in an IND that the
proceed with the planned
review division determines
clinical trials, but that
are not serious enough to
additional information is
justify delaying clinical
necessary to complete or
studies, the division may
correct the IND file, or that
either telephone or forward
there are issues that need to be
a deficiency letter to the
addressed prior to a marketing
sponsor.
application (NDA) submission.
