INDA- Investigation New Drug Application, useful presentation for UG and PG students

1. IND (Investigational New Drug Application)
&
NDA (New Drug Application)
Prepared by
Dr. Jigar Vyas
Professor
Sigma Institute of Pharmacy

2. DRUG DEVELOPMENT
 Development of a new
therapeutic drug is a complex,
lengthy and expensive process
 costs nearly 900 million dollars
and an average of 15 years.

3. THE TWO TRANSLATIONAL
BLOCKS
Basic
Biomedical
Research
Clinical
Science
and
Knowledge
Goal:
Improved
Health
Translation from
basic science to
human studies
Translation of
new knowledge
into clinical practice

4. DRUG DEVELOPMENT PROCESS

5. IND (Investigational New Drug
Application)

6. IND (Investigational New Drug
Application)
 FDA's role in the development of a new drug
begins when the drug's sponsor has screened the
new molecule for pharmacological activity and
acute toxicity potential in animals, wants to test its
diagnostic or therapeutic potential in humans
 The molecule changes in 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

7. TYPES OF IND
 Investigator IND
o Submitted by a physician who both initiates and conducts an
investigation, and under whose immediate direction the
investigational drug is administered or dispensed.
o 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
o Allows FDA to authorize use of an experimental drug in an
emergency situation
o Does not allow time for submission of an IND in accordance
with 21CFR , Sec. 312.23 or Sec. 312.34
 Treatment IND
o 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

8. CLASSIFICATION OF IND
 Commercial
o Permits sponsor to collect data on clinical safety
and effectiveness needed for application for
marketing in the form of NDA
 Research (non-commercial)
o Permits the sponsor to use drug in research to
obtain advanced scientific knowledge of new
drug
o No plan to market the product

9. CONTENT OF IND
In three broad areas:
 Animal Pharmacology and Toxicology Studies –
o An assessment as to whether the product is reasonably safe for
initial testing in humans
o Any previous experience with the drug in humans
 Manufacturing Information
o composition, manufacturer, stability, and controls used for
manufacturing the drug
 Clinical Protocols and Investigator Information
o Commitments to obtain informed consent from the research subjects,
to obtain 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 days before
initiating any clinical trials. 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

10. FORMAT OF IND
A. Cover sheet (Form FDA-1571)
o Name, address, telephone of sponsor
o Identification of phases
o Commitment not to begin CT until IND approval
o Commitment by IRB- Form 56
o Commitment for conducting CT- accordance with regulations
o Name, title – Monitor
o Name, title – person(s) for reviewing
o Name, Address of CRO, if any
o Signature of sponsor
B. Table of contents
C. Introductory statement & general investigational plan
D. Investigators brochure
E. Study protocol
F. Investigator facilities & IRB data
G. Chemistry manufacturing & control data
H. Pharmacology & toxicology data
I. Previous human experience

11. RESOURCES FOR IND
APPLICATIONS
• Pre-Investigational New Drug Application (IND)
Consultation Program
o Offered by CDER (Center for Drug Evaluation and
Research) to foster early communications between
sponsors and new drug review divisions in order to
provide guidance on the data necessary to warrant IND
submission.
• Guidance Documents for INDs
o documents are prepared for FDA review staff and
applicants/sponsors to provide guidelines to the
processing, content, and evaluation/approval of
applications and also to the design, production,
manufacturing, and testing of regulated products

12. GUIDANCE DOCUMENTS
For the complete list of CDER guidance, please see
the Guidance Index
 Safety Reporting Requirements for INDs and BE/BA Studies
 CGMP for Phase 1 Investigational Drugs
 Exploratory IND Studies
 Content and Format of Investigational New Drug Applications (INDs) for
Phase 1 Studies of Drugs, Including Well Characterized, Therapeutic,
Biotechnology-Derived Products
 Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including
Well-Characterized, Therapeutic, Biotechnology-Derived Products
 Bioavailability and Bioequivalence Studies for Orally Administered Drug
Products
 IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products
for the Treatment of Cancer
 Guideline for Drug Master Files
A Drug Master File (DMF) is a submission to the Food and Drug Administration
(FDA) that may be used to provide confidential detailed information about
facilities, processes, or articles used in the manufacturing, processing,
packaging, and storing of one or more human drugs.
 Required Specifications for FDA's IND, NDA, and ANDA Drug Master File
Binders
 Immunotoxicology Evaluation of Investigational New Drugs

13. LAWS,REGULATIONS,
POLICIES, PROCEDURES
 The Federal Food, Drug, and Cosmetic Act is the
basic food and drug law of the U.S The law is
intended to assure consumers that
foods are pure and wholesome, safe to eat, and
produced under sanitary conditions;
drugs and devices are safe and effective for their
intended uses;
cosmetics are safe and made from appropriate
ingredients;
all labeling and packaging is truthful, informative, and
not deceptive.

14. LAWS,REGULATIONS,
POLICIES, PROCEDURES
Cont…..
 Code Of Federal Regulations (CFR)
o The final regulations published in the Federal Register (daily published
record of proposed rules, final rules, meeting notices, etc.) are collected in
the CFR.
o The CFR is divided into 50 titles that represent broad areas subject to
Federal regulations.
o The FDA's portion of the CFR interprets the The Federal Food, Drug, and
Cosmetic Act and related statutes. Section 21 of the CFR contains most
regulations pertaining to food and drugs.
21CFR Part 312 Investigational New Drug Application
21CFR Part 314
INDA and NDA Applications for FDA Approval to
Market a New Drug (New Drug Approval)
21CFR Part 316 Orphan Drugs
21CFR Part 58 Good Lab Practice for Nonclinical Laboratory
[Animal] Studies
21CFR Part 50 Protection of Human Subjects
21CFR Part 56 Institutional Review Boards
21CFR Part 201 Drug Labeling
21CFR Part 54 Financial Disclosure by Clinical Investigators

15. LAWS,REGULATIONS,
POLICIES, PROCEDURES
Cont…..
 CDER's Manual of Policies and
Procedures (MaPPs)
MaPPS are approved instructions for
internal practices and procedures
followed by CDER staff to help
standardize the new drug review
process and other activities.

16. IND REVIEW PROCESS

17. Guidance for preparation of IND
Reference to document:
http://www.fda.gov/cder/regulatory/appli
cations/ind_page_1.htm

18. NDA (NEW DRUG APPLICATION)

19. NDA (New Drug Application)
 The vehicle through which drug sponsors
formally propose that the regulatory body
approve a new pharmaceutical for sale and
marketing.
 Form 44
 The data gathered during the animal
studies and human clinical trials of an
Investigational new product become part of
the NDA.

20. GOAL OF NDA
Provide enough information to permit FDA reviewers to
establish the following:
 Safety & effectiveness of drug?
 Benefits overweigh risks?
 Is the drug’s proposed labelling (package insert)
appropriate, and what should it contain?
 Are the methods used in manufacturing (Good
Manufacturing Practice, GMP) the drug and the
controls used to maintain the drug’s quality adequate
to preserve the drug’s identity, strength, quality, and
purity?
Risk Benefit

21. NDA CONTENTS
1. Introduction
o Brief description of the drug and the therapeutic class to which
it belongs
2. Chemical and
pharmaceutical information
3. Animal Pharmacology
4. Animal Toxicology
5. Human/Clinical Pharmacology phase I
6. Therapeutic exploratory trials (Phase II)
7. Therapeutic confirmatory trials (Phase III)
8. Special Studies
o Geriatrics, pediatrics, pregnant or nursing women
9. Regulatory status in other countries
10. Prescribing information
11. Samples and Testing Protocol/s

22.  Once the application is submitted, the FDA has 60
days to conduct a preliminary review which will
assess whether the NDA is "sufficiently complete to
permit a substantive review”
 If everything is found to be acceptable, the FDA will
decide if the NDA will get a standard or accelerated
review and communicate the acceptance of the
application and their review choice in another
communication known as the 74-day letter
 A standard review implies an FDA decision within
about 10 months

23. CONTENTS OF ANDA
Data for a drug already approved in the country
1. Introduction
2. Chemical and pharmaceutical information
3. Marketing information
4. Special studies conducted with approval
of Licensing Authority

24. REQUIREMENTS FOR SIMILAR
PRODUCTS
GENERIC DRUGS
 Drug product that is comparable to any innovator
drug product in dosage form, strength, route of
administration, quality, performance characteristics
and intended use but is produced & distributed
without patent application.
 This drug have already been approved via an NDA
submitted by another maker are approved via an
Abbreviated New Drug Application (ANDA), which
does not require all of the clinical trials normally
required for a new drug in an NDA
o No need for preclinical and clinical data
o Bioequivalence

25. REQUIREMENTS FOR SIMILAR
PRODUCTS Cont….
BIOLOGICS
 Biologics such as vaccines and many recombinant
proteins used in medical treatments are generally
approved by FDA via a Biologic License Application
(BLA), rather than an NDA.
 Manufacture of biologics is considered to differ
fundamentally from that of less complex chemicals,
requiring a somewhat different approval process.

26. REQUIREMENTS FOR SIMILAR
PRODUCTS Cont….
MEDICAL DEVICES
 Medical devices are approved by a variety of methods
depending on the class of the device
 Class I: Devices that do not require premarket approval
Eg; Dental floss
 A Pre-market Application (PMA) largely equivalent to an
NDA is required for class III devices.These tend to be
devices that are permanently implanted into a human body
or may be necessary to sustain life.
Eg; artificial heart
 510(k) approval that shows the device is equal to or better
than a predicate device already on the market is required for
class II devices.
Eg;Diagnostic tests, cardiac catheters, and amalgam
alloys used to fill cavities, hearing aids

27. REQUIREMENTS FOR SIMILAR
PRODUCTS Cont….
Drugs for life threatening/serious
disease/relevance to India
Clinical and toxicological data may be
abbreviated, deferred or omitted as per the
licensing authority

28. NDA REVIEW PROCESS

29. REFERENCES
 http://www.hhs.gov
 http://www.fda.gov/regulatoryinformation/leg
islation/federalfooddrugandcosmeticactfdca
ct
 Gupta S. K; Basic principles of clinical
research and methodology.

30. QUESTIONS???

31. THANK YOU