Transcript What Is An IND?

Investigational New Drug
Application (INDA)
PRESENTED
BY:Dillip Kumar Jena
Dept of pharmaceutics & pharmaceutical Technology
LMCP
7/17/2015
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WHAT I WILL TELL
• INTRODUCTION
• REGULATORY ASPECT
• TYPE OF IND
• REQUIERMENT IND
• CONTENT OF IND
• IND AMENDMENT
• ANNUAL REPORT OF IND
• CONCLUSION
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What is INDA
General introduction
this data and information is generated and
gathered from three broad areas:
Animal P’cology & Toxicology studies
Manufacturing information
Clinical Protocols & Investigator
Information
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Regulation
• The regulations in 21 CFR 312 cover
procedures and requirements for
Investigational New Drug Applications
(INDs)
• These regulations define the roles and
responsibilities of FDA reviewers, IND
sponsors, and clinical investigators
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Definitions
Sponsor
• A sponsor is an individual, company,
institution, or organization that takes
responsibility for and initiates a
clinical study (21 CFR 312.3(b),
312.50)
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Sponsor
A sponsor is responsible for:
• Selecting qualified investigators
• Ensuring study monitoring
• Maintaining an effective IND, and
• Ensuring AE risk information is
provided to the FDA and
investigators
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Definitions
Investigator
• An investigator is an individual under
whose immediate direction the study
drug is administered or dispensed. If
a team is involved, the leader is the
investigator; other team members are
sub-investigators
(21 CFR 312(b), 312.60)
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Definitions
Sponsor-Investigator
• A sponsor-investigator is an individual who
both initiates and conducts a study and
under whose immediate direction the study
drug is administered or dispensed. This
person must follow the requirements
pertaining to a sponsor and those pertaining
to an investigator
(21 CFR 312(b))
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IND Requirements
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TYPE OF IND
1. Commercial IND
2. Emergency use IND
3. Treatment IND
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Objective
• To focus FDA’s attention during early phase
of clinical research on assuring the safety of
human test subjects.
• To provide sponsors with a greater measure
of flexibility in conducting Phase 1 trials.
• To facilitate consultation between FDA &
sponsors, especially after there is an
indication that the new drug is safe and
efficacious in humans.
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IND Content Requirements
21 CFR 312.23
• Cover Sheet (Form FDA 1571)
• Table of Contents
• Introductory Statement & General investigational
plan
• Investigator’s Brochure
• Protocols
• Chemistry, Manufacturing & Control Information
• Previous Human Experience with the Investigational
Drug
• Additional Information
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Cover Sheet (form FDA
1571)
• The form is provided for basic information
like name of drug, submission date,
sponsor identification, phase of proposed
clinical investigation, sponsor
commitments, identification of clinical
monitor and safety evaluator, information
regarding transfer of responsibilities to a
contract research organization.
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Table of Contents
Drug Name®
IND table of contents
Item title
volume/page
Introductory statement &
general investigational plan…
(i) Introductory statement….
(ii) summary of previous human experience
with drug…….
(iii) If the drug has been withdrawn from
Investigation/Marketing……
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iv) General Investigational Plan…..
5 Investigator’s Brochure…….
6 Protocol……..
7 Chemistry, Manufacturing & Control
Information…
(a) Drug substance…………
(b) Drug Product…………….
(c) Placebo (if applicable)…
(d) Labeling…………………….
(e) Environmental Analysis ….
8 Pharmacology & Toxicology
Information…….
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9)Previous Human Experience with the
Investigational Drug…….
(i) Summary of Previous Human
Experience….
(ii) If the drug is a combination of drug
previously investigated/marketed…….
(iii) If the drug has been marketed outside
the
United States……
10 Additional Information (as applicable for
radioactive drugs or drugs with
dependence or abuse potential)….
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Introductory Statement &
General Investigational Plan:
It consists of four subsections:
1st subsection: (introductory statement)
• Name of drug
• P’cological Class
• Structural formula
• Route of administration
• Broad objectives
• Planned duration of the proposed clinical
investigation
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2nd subsection:
• Brief summary of any previous human
experience with the drug, including
investigational or marketing experience in
other countries
3rd subsection:
• It is a statement as to whether or not the
drug has been withdrawn from
investigation or marketing in any country
for any reason of safety or efficacy
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4th subsection:
• Brief description of overall
investigational plan for drug during
the following year like: Indications to
be studied, kinds of clinical trials to
be conducted in first year
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Investigator’s Brochure (IB)
• Sponsor must provide to all clinical
investigators, not required for sponsor
investigators (21 CFR 312.55). It must
include:
–
–
–
–
Brief product description
Pharm/tox summaries
Previous human experience
Description of anticipated risk and any special
monitoring needs
– Updates as appropriate
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Drug Name®
Investigator's Brochure
Table of contents
Page
Introduction……………………..
Chemistry……………………….
Physical Properties……
How Supplied…………….
Pharmacology………………….
Specific Effect Studies…
General Studies………….
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Toxicology………………………..
Acute Toxicity…………….
Multidose Toxicity……….
Special Toxicity Studies………
Reproductive Studies……
Mutagenicity Studies…….
Pharmacokinetics………………
Preclinical…………………….
Clinical………………………….
Clinical Trial……………………….
Phase 1…………………………
Phase 2/3… ………………….
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Safety/Efficacy Overview
Safety…………………………..
Efficacy………………………..
Possible Risks and Side Effects…
References………………………….
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5 Protocols
• Phase 1 protocol provides an outline of
investigation by specifying information such
as estimated number of test subjects,
inclusion/exclusion criteria and dosing plan
• Phase 2 and Phase 3 protocols are detailed,
describing all aspects of the studies, such
that any deviation in a design if required, it
can be established in the protocol from the
beginning.
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All the protocols are required to contain the
following elements:
• Statement of the objectives and purpose of
the study
• Patient inclusion/exclusion criteria
• Estimate of number of patients to be studied
• Description of study design
• Dosing information including planned
maximum dosage and duration of individual
patient exposure to the Drug
• Description of the observations and
measurements planned to fulfill the study
objectives
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CMC Information
• Emphasis in Phase I is on identification and control of
raw materials and new drug substance, including
information on any placebo as well
• Even for Phase I, need enough information to assess
safety
• Extent of expected information increases as drug
development proceeds
• Throughout product development, good
documentation of all manufacturing and testing steps
is essential
• Deficiencies in CMC information can result in clinical
hold
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Other IND Items
• Previous human experience needs to
be included (if applicable)
• Additional information such as preIND meeting minutes or critical
references should be included as well
• Serial numbering of pages of an IND
is required (21 CFR 312.23(11)(e))
as this facilitates reference if the FDA
has questions
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IND Protocol Amendments
21 CFR 312.30
• A new protocol
• Safety or design related changes to an
existing protocol
• New investigator (notification is required
within 30 days of being added)
• These should be submitted to the FDA
prior to implementation
• IRB approval is needed prior to
implementation
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IND Information
Amendments
21 CFR 312.31
Information amendments advise the
FDA of:
• New tox, CMC or other technical
information
• Notice of discontinuance of a clinical
study
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IND Safety Reports:
• If a sponsor notify any unexpected
fatal / life threatening experience
associated with the use of the drug
requires to notify the FDA by
telephone no later than 3 working
days after receipt of the information,
followed by a written report within
10 days.
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Annual Reports
21 CFR 312.33
• To be submitted within 60 days of the
anniversary of “in effect” date
• Include enrollment, demographic and
conduct status information for each study
• Adverse event summaries (safety reports,
deaths, dropouts)
• Drug action information
• Preclinical study status information
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Annual Reports (cont’d)
• CMC change information
• Revised/updated investigator
brochure with revisions described
• Foreign marketing experience
• Outstanding business with the FDA
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Withdrawal of an IND
It is option of a sponsor to withdraw
an IND at any time without
prejudice.
On withdrawn, sponsor must notify
the FDA.
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Conclusions
Two major outcomes from the IND discussion
are:
• 30 days after an IND is submitted to the
FDA, if the sponsor has not heard anything
from the FDA it can be assumed that the
drug is not on a clinical hold and clinical
trials may be started
• The Investigator’s Brochure, which will be
used during that important first clinical
study and in every clinical study thereafter,
acts as the approved labeling for the drug
while it is under an IND
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List of references
1.www.fda.gov/cder/about/history/time1.ht
m
2.Remington the science and practice of
pharmacy, 20th edition, Lippincott,Williams
& Wilkins, page no: 930-943
3. New Drug Approval Process: second Edition,
Revised and Expanded, edited by Richard A.
Guarino page no: 39-64, 243-263
4.www.fda.gov/cder/handbook/indbox.htm
5.www.fda.gov/cder/handbook/ndabox.htm
6.www.fda.gov
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