INVESTIGATIONAL NEW DRUG [IND] APPLICATION SUBMISSION (1).pdf

IND Application is an important stage of Drug development before clinical trials. This ppt contains an outline of IND submission to the FDA.

1. Drug
Approval INVESTIGATIONAL NEW DRUG [IND]
APPLICATION SUBMISSION
AMEENA KADAR K A
FIRST SEM M PHARM
PHARMACY PRACTICE
SANJO COLLEGE OF PHARMACEUTICAL STUDIES

2. CONTENTS
DEFINITION
INTRODUCTION
CONTENTS OF IND APPLICATION
TYPES OF IND
RESOURCES OF IND APPLICATION
GUIDANCE DOCUMENTS FOR IND
CODE OF FEDERAL REGULATIONS
MANUAL OF POLICIES AND PROCEDURES
EMERGENCY USE OF AN INVESTIGATIONAL DRUG OR BIOLOGIC
THE IND PROCESS AND REVIEW PROCEDURES
REFERENCES

3. What is IND?
An IND is a submission to the FDA requesting permission to
initiate a clinical study of a new drug product.
The Federal Food, Drugs, and Cosmetic Act require that all
drugs have an approved marketing application before they can be
shipped to the commercial industry.

4. New drug
The proposed trial, and the
The entire clinical development plan described in the IND is
designed to minimize risk to the trial subjects.
When preparing an IND, and throughout the drug development
process, the primary goal of the sponsor should be to demonstrate
to the FDA that the

5. A new chemical entity not approved for the indication is
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.
An IND would be required to conduct a clinical trial if the drug
is:
All clinical studies where a new drug is administered to human
subjects require an IND.

6. IND Application accompanied by
IND application cover
Investigator’s statement
Certification requirement & mandatory registration and
reporting of results for applicable clinical trials

8. 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
on earlier notification by FDA that the clinical investigations
in the IND may begin.
INDA is reviewed to ensure the protection of rights and safety
of human subjects
The sponsor may begin clinical trail 30 days after submission.
An IND application may go into effect:

9. Name, address, telephone. no of the sponsor of the drug
Name, the title of the person responsible For monitoring the
conduct and progression of the investigation
Investigator’s brochure
Name and address of any CRO involved in the study
Name of the drug
Drug structure formula
Route of administration
USFDA REQUIREMENTS
Introductory statement and general investigational plan:

10. Indication of drug
Types of studies
Estimated number of subjects
A complete description of the drug
Method of preparation
Analytical methods
Description of the investigational plan :
Chemistry and manufacturing:
Mechanism of action of the drug
Drug absorption, distribution, etc
Pharmacology and toxicology :

11. FORMAT OF IND
Name, address, and telephone of the sponsor
Identification of phases
Commitment not to begin CT until IND approval
Commitment by IRB- Form 56
Commitment to conducting CT- in accordance with regulations
Name, title – Monitor
Name, title – person(s) for reviewing
Name, Address of CRO, if any
Signature of sponsor
Cover sheet (Form FDA-1571)

12. Table of contents
Introductory statement & general investigational
plan
Investigators brochure
Study protocol
Investigator facilities & IRB data
Chemistry manufacturing & control data
Pharmacology & toxicology data
Previous human experience

13. CONTENTS OF IND APPLICATION

14. Animal Pharmacology and Toxicology Studies:
Preclinical data permits an assessment as to whether the
product is reasonably safe for initial testing in humans.
Also included is any previous experience with the drug in
humans (often foreign use).
CONTENTS OF IND
The IND application must contain information in three broad
areas:
1.

15. 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.

16. 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 fulfill their clinical trial duties.
Finally, commitments to obtain informed consent from the
research subjects, to obtain a review of the study by an
institutional review board (IRB), and to adhere to the
investigational new drug regulations.
Once the IND is submitted, the sponsor must wait 30
calendar days before initiating any clinical trials.

17. During this time, FDA has an opportunity to review the
IND for safety to assure that research subjects will not be
subjected to unreasonable risk.
TYPES OF IND
Investigator IND
Emergency Use IND
Treatment IND

18. An 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. A physician might submit a research IND to propose
studying an unapproved drug, or an approved product for a new
indication or in a new patient population.
Emergency Use IND allows the FDA to authorize the use of an
experimental drug in an emergency that does not allow time for
submission of an IND. It is also used for patients who do not meet
the criteria of an existing study protocol, or if an approved study
protocol does not exist.

19. 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.
Commercial
Research (non-commercial)
There are two IND categories:
1.
2.

20. Commercial IND: Permits the sponsor to collect data on clinical
safety and effectiveness needed for application for marketing in
form of NDA.
Non-Commercial IND: Permit sponsor to use the drug in
research of early clinical investigations to obtain advanced
scientific knowledge of new drugs. No plan to market the
product

21. Resources for IND Applications
Pre-IND Consultation Program
CDER's Pre-Investigational New Drug Application (IND)
Consultation Program fosters early communications between
sponsors and new drug review divisions to provide guidance on
the data necessary to warrant IND submission.
The review divisions are organized generally along therapeutic
classes and can each be contacted using the designated Pre-
IND Consultation List.

22. Guidance documents represent the Agency's current thinking
on a particular subject. These documents provide FDA
review staff and applicants/sponsors with guidelines to the
processing, content, and evaluation/approval of applications
and also to the design, production, manufacturing, and
testing of regulated products. They also establish policies
intended to achieve consistency in the Agency's regulatory
approach and establish inspection and enforcement
procedures.
Guidance Documents for INDs

23. Because guidances are not regulations or laws, they are not
enforceable, either through administrative actions or through the
courts. An alternative approach may be used if it satisfies the
requirements of the applicable statute, regulations, or both.
Code of Federal Regulations (CFR)
The final regulations published in the Federal Register (daily
the published record of proposed rules, final rules, meeting
notices, etc.) are collected in the Code Of Federal Regulations
(CFR).

24. The CFR is divided into 50 titles that represent broad areas
subject to Federal regulations.
The FDA's portion of the CFR interprets the Federal Food,
Drug, and Cosmetic Act and related statutes.
Section 21 of the CFR contains most regulations pertaining
to food and drugs.
The regulations document all actions of all drug sponsors
thatare required under Federal law.

25. Manual of Policies and Procedures (MaPPs)
CDER's Manual of Policies and Procedures (MaPPs) are
approved instructions for internal practices and procedures
followed by CDER staff to help standardize the new drug
review process and other activities. All MAPPs are available for
the public to review for a better understanding of office policies,
definitions, staff responsibilities, and procedures.

26. Emergency Use of an Investigational Drug or Biologic-
Information Sheet
The Guidance for Institutional Review Boards and Clinical
Investigators contains information on Obtaining an
Emergency IND, Emergency Exemption from Prospective
IRB, Approval Exception from Informed Consent, and
Requirement Planned Emergency Research, Informed
Consent Exception.
Emergency Use of an Investigational Drug or Biologic

27. Physician Request for a Single Patient IND for
Compassionate or Emergency Use.
Instructions for Sponsors of Emergency Investigational New
Drug (EIND) Applications for Antimicrobial Products. From
the Office of Antimicrobial Products, Division of Antiviral
Products

28. THE IND PROCESS AND REVIEW PROCEDURES

30. Once the IND is stamped as received, it is sent to the review
division within CDER.
• On arrival at the review division, it is critically evaluated by
several reviewers of
o Chemistry
o Biopharmaceutics
o Medical
o Statistics
o Microbiology
o Pharmacology /toxicology sections

31. All these areas review the data submitted with the primary
purpose to ensure the safety of the individual enrolled in the
study.
Once an IND is submitted, the study can’t be initiated until a
period of 30 days.
If there are any major issues relating to the safety of the
volunteers in the proposed study, the FDA can institute a
clinical hold.
Sponsors should submit an annual report that provides the
FDA with a brief update on the progress of all investigations
included in the IND.

32. It should contain the following:
• Individual study information.
• Summary of the study.
• Listing of any significant foreign marketing developments
with the drug e.g. approval in another country.

33. IND Annual Reports
Individual study information
Summary Information
The general investigational plan for the coming year.
If the investigator brochure was modified during the year, a list of the
changes along with a copy of the new brochure.
A listing of any significant foreign marketing developments with the drug,
e.g., approval in another country or withdrawal or suspension of marketing
approval.
The IND regulations require IND sponsors to submit an annual report that
provides the FDA with a brief update on the progress of all investigations
included in the IND. The annual report must contain the following information:

35. REFERENCES
Investigational New Drug Applications Prepared and Submitted by Sponsor-Investigators
Guidance for Industry; U.S. Department of Health and Human Services Food and Drug
Administration Center for Drug Evaluation and Research (CDER) Center for Biologics
Evaluation and Research (CBER)