Transcript INDA - PharmaQuesT

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What is INDA ?
Types of INDAs
Objectives of INDAs
Format & Contents of an INDA
IND Safety reports
IND Annual Reports
IND Review Process
Withdrawal of an IND
Inactive Status
References
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What is INDA ?
(Fig. Flow chart
illustrating the various
steps in preclinical and
clinical development of
pharmaceutical Products)
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INDA is a vehicle through which a sponsor advances to the next
stage of drug product development known as clinical trials (human
trials) .
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It includes data and information in three broad areas:
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Animal Pharmacology and Toxicology Studies
Manufacturing Information
Clinical Protocols and Investigator Information
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The regulations in 21 CFR 312 cover procedures and requirements for
Investigational New Drug Applications (INDAs) .
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These regulations define the roles and responsibilities of FDA
reviewers, IND sponsors, and clinical investigators .
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Sponsor
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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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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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Investigator
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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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An investigator is responsible for :
Ensuring the study is conducted according to the plan
Protecting the rights, safety and welfare of subjects, and
Control of drug under investigation
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Sponsor-Investigator
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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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1.
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Commercial INDs
Emergency use INDs
Treatment INDs
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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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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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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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Drug Name®
IND table of contents
Item Title
volume/page
3 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…
iv) General Investigational Plan…..
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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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It consists of four subsections:
1st subsection: (Introductory statement)
 Name of drug
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P’cological Class
 Structural formula
 Route of administration
 Broad objectives
 Planned duration of the proposed clinical investigation
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2nd subsection:
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Brief summary of any previous human experience with the
drug, including investigational or marketing experience in
other countries .
3rd subsection:
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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:
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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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Sponsor must provide to all clinical investigators, not
required for sponsor investigators (21 CFR 312.55).
It must include:
Brief product description
 Pharmacology/toxicology 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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Phase 1 protocol provides an outline of investigation by
specifying information such as estimated number of test
subjects, inclusion/exclusion criteria and dosing plan.
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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:
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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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Drug Substance
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Physical, chemical or biological characteristics of the drug substance,
along with the name and address of the manufacturer
Description of the general method of preparation, identification of the
analytical methods and acceptable limits used to assure the identity,
purity and strength of the drug substance
Stability data must be sufficient to support the stability of drug
substance throughout the preclinical and proposed clinical studies
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Drug Product
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Qualitative & Quantitative compositions
Manufacturing facility, manufacturing and packaging procedure,
identification of analytical methods, acceptable limits used to assure
identity, purity, and strength of components and finished products
Stability data to support duration of proposed clinical studies.
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Labeling
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A copy of all labels and labeling to be provided to each clinical
investigations must be submitted.
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Environmental Analysis
Identification and quantities of any chemical substances emitted
during the manufacture of the product, use of resources and energy,
etc.
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Previous Human Experiences with the
Investigational Drug
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Such findings if available must be submitted whether drug is
marketed in U.S. or other foreign country.
Additional Information
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Any information that sponsor believes will aid in the evaluation of
the application.
IND Amendments:
Protocol Amendments
Information Amendments
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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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(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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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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On sponsor’s request FDA may place an IND on inactive status if no
subjects have entered clinical studies for at least two years or if the
IND has been on clinical hold for at least one year.
After remaining on inactive status for five years, the FDA may
terminate an IND.
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1.www.fda.gov/cder/about/history/time1.htm
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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Thanks to All