1. GLOBAL SUBMISSION OF IND, NDA,
ANDA
LOKESH THAKRE
M. PHARM (PHARMACEUTICS)
SPER JAMIA HAMDARD New Delhi

2. OUTLINES
1. Investigational new drug application (IND)
▪ Types of IND
▪ General information
▪ Content and format
▪ IND review flow chart
2. New drug application (NDA)
3. Abbreviated new drug application (ANDA)

3. INVESTIGATIONAL NEW DRUG
APPLICATION(IND)
▪ The term Investigational New Drug refers to a drug developed by pharmaceutical or
biotech company or any individual organization that is ready for clinical trial on human.
▪ An Investigational New Drug (defined under 21 CFR part 312.23 as) an application
from a sponsor submitted to Food and Drug Administration requesting the permission
to initiate clinical study of new drug on human being.
▪ After the preclinical trial when the new drug entity screened for pharmacological and
toxicological study the sponsor need the FDA permission to conduct clinical trial on
human.

4. ▪ Once the IND submitted to FDA, the sponsor or clinical investigator must wait for 30
days or a month to initiate clinical trial.
▪ Because in this duration the FDA and local Institutional Review Board (IRB) check and
review the IND application for further approval.
▪ If the FDA accept the NDA request within the 30 days of IND submission, the sponsor
can begin the clinical testing of new drug on human being.
▪ At any time duration FDA can terminate or hold the clinical trial, if data furnished to FDA
indicate any toxicity or not compete with FDA’s benefit-risk assessment.

5. Types of IND
1. Investigator IND:- It is submitted by a physician who initiates and conducts an
investigation, under whose immediate direction the investigational drug is
administered or dispensed.
2. Emergency use IND :- This IND allow FDA to authorize use of experimental drug in
emergency situation.
3. Treatment IND :- It is submitted for experimental drugs showing promise in clinical
testing for serious or immediately life-threatening conditions.

6. Classification of IND
▪ COMMERCIAL IND
This is submitted by company to get market
approval of new drug.
▪ NON COMMERCIAL (RESEARCH) IND
It allow the sponsor to use the drug in
research to obtain advanced scientific
knowledge of new drug.

7. General information for filling
▪ A
InN
imalD
pharmacology and toxicology studies :-the preclinical data helpful in assessing
whether the product safe for initial testing in human.
▪ Manufacturing information:-
Information regarding the composition, manufacturer, stability, and
manufacturing the drug substance and the drug product.
▪ Clinical protocol & Investigator information :-
controls used for
Detailed protocols for proposed clinical studies to asses whether the initial phase trial will
expose subject to unnecessary risk.
It also include the qualification information of clinical investigator professional (physician) to
assess whether they are qualified to fulfil their clinical duties.

8. Resources for IND
▪ Pre – IND consultation program
CDER’s pre- Investigational New Drug Consultation Program fosters early
communication between sponsor and drug review division to provide guidance on the
data necessary to warrant IND submission.

9. Format And Content Of IND
▪ Cover sheet (Form FDA- 1571)
a) Name, address telephone no of sponsor.
b) Identification of phases.
c) Commitment of not to begin the clinical trial until the IND approval
d) Commitment with IRB
e) Commitment to conduct the clinical trials according to applicable regulatory
requirement.
f) Name and address of contract research organization (CRO).
g) Signature of sponsor.

10. ▪ Table of content
▪ Investigators brochure
▪ Protocols
▪ Chemistry, Manufacturing, Control information (CMC)
▪ Pharmacological and toxicological study
▪ Previous experience with Investigational drug
▪ Additional information includes
a) Drug dependency/drug abuse
b) Radioactive drug
c) Paediatric study

12. NEW DRUG APPLICATION
(NDA)

13. NDA
▪ When clinical studies confirm that a new drug is relatively safe and effective, and will
not pose harmful affect to patients, than the manufacturer can files a New Drug
Application (NDA).
▪ NDA is an application submitted to the FDA for permission to market a new drug. To
obtain this permission a sponsor submits preclinical and clinical test data to NDA for
analyzing the drug information and description of manufacturing procedures.
▪ When the NDA received by agency, so it undergoes for technical screening to ensure
that data submitted by sponsor is sufficient for filing application or not.

14. ▪ At the conclusion when FDA complete all review, there are three possible action can
send to sponsor
i. Not approvable
ii. Approvable
iii. Approval

15. NDA Classification Code
▪ CDER classify the new drug application according to types of drug to be submitted and it’s
uses
Type 1 – New Molecular Entity
Type 2- New Active Ingredient
Type 3- New Dosage Form
Type 4- New Combination
Type 5- New Formulation Or Other Differences (eg. New Indication, New Application, Or
New Manufacturer)
Type 6- Previously Marketed But WithoutAn Approved NDA

16. Type 7- Rx to OTC
Type 8- New Indication Or Claim For Existed Marketed Product
Format And Content For Filling NDA
The application is to be submitted in Common Technical document (CTD) Format with following
section-
1. Form FDA- 356h (application to market a new drug, new biologic, or an antibiotic drug for
human use)
2. Form FDA-3397 (user fee cover sheet)
3. Form FDA-3331 new drug application field report)

17. 4. Index
the archival copy of NDA contains comprehensive index by volume number and page
number
5. Summary
the summary contain following information –
a) Text of the labeling
b) Pharmacological class of drug
c) Brief information of marketed history (if any)

18. 6. chemistry, manufacturing and control data
7. Non clinical pharmacological and toxicological section
8. Microbiological (for anti microbial drug)
9. human pharmacokinetic and bioavailability section
10. Statistical data( eg. Method and analysis of clinical data)
11. Sampling and labeling
12. Pediatric use section
13. Patent information and certification
14. Case report form and tabulation

19. Format of original NDA
It is submitted in two copies –
1. Archival copy
▪ The applicant must submit a complete archival copy of the NDA that contains the
complete information and serve as permanent record.
▪ FDA will maintain the archival copy during the review of the NDA to
permit individual reviewers to refer the information that is not contained in their
particular technical sections of the NDA.
2. Review copy - it is divided in 6 technical section
▪ CMC

20. ▪ Non clinical pharmacological and toxicological
▪ Human pharmacokinetic and bioavailability
▪ Clinical data
▪ Microbiological data
▪ Statistical study (if any)

22. Abbreviated New
Drug Application

23. ANDA
▪ It’s an application made for approval of Generic Drugs, In this application the sponsor
is not required to reproduce the clinical and preclinical studies that were done for
brand name product, but the sponsor or generic drug manufacturer must demonstrate
that the drug has same bioequivalent to previously approved branded drug.
▪ The ANDA is submitted to Food and drug administration (FDA) for review and
potential approval of generic drug product.
▪ Once the drug approved, the applicant may manufacture and market the product to
provide safe, effective and low cost medicine alternate to brand name drug.
▪ Once the generic drug approved, it is listed in FDA’s Approved drug product with
Therapeutic Equivalence Evaluations (Orange book).

24. ▪ The generic drug termed “Abbreviated” because there is no requirement to submit
clinical (human) and preclinical(animal) data to establish safety and effectiveness.
▪ The bioequivalence study plays a major role in the approval of generic drug, it should
have same bioequivalence data when compare with Innovator drug (branded drug).
▪ According to Drug price competition and patent term restoration act (Hatch – Waxman
Amendments) bioequivalence study is base for approving generic copy of drug
product.
▪ TheseAmendments permit FDA to approve applications to market generic versions of
brand-name drugs without repeating costly and duplicative clinical trials to establish
safety and efficacy.

25. ▪ In addition, this amendment also give right toANDA applicant to challenge the patent in
court prior to marketing as well as 180 days generic drug exclusivity.
ANDA Forms
1. Form FDA- 356h (application to market a new or abbreviated drug, biologic for human
use)
2. Form FDA- 3794 (Generic drug user fee cover sheet)
3. Form FDA- 3674 (certification of compliance)
4. Drug Master Files

26. Under the section
314.94 (a) (12), a
patent certification
must contain one of
the following –
Paragraph 1
certification
Paragraph 2
certification
Paragraph 3
certification
Paragraph 4
certification

27. ▪ A para IV filling is subset of ANDA application, where the generic applicant is claiming
that the patent they are targeting is unenforceable either due to –
➢Invalid or
➢Not infringed
➢Or both Invalid and non infringed by their product.
▪ The applicant must notify to the patent holder about the submission of ANDA. If the
patent holder files an infringement sue against the generic applicant within 45 days of
theANDA notification,
▪ So the FDA postponed the market approval of generic drug for 30 month unless or
before that time patent is expire or judged as invalid or not infringed
▪ This 30-month postponement allows the patent holder time to assert its patent rights
in court before a generic competitor is permitted to enter.

28. Electronic Submission
▪ The FDA do not accept paperANDA’s. all ANDA submission must be in eCTD format.
▪ If the eCTD format is less than 10 GB so must use FDA electronic submission
gateway (ESG).
▪ if the eCTD format is greater than 10 GB, it may be submitted via physical media
(DVD/USB drive).to the CDER document room or via ESG.

29. ▪ The CTD format is comprises of following modules-
✓ Module 1 : Administrative information and Prescribing information
✓ Module 2 : Summaries
✓ Module 3 : Quality
✓ Module 4 : Nonclinical
✓ Module 5 : Clinical

34. ANDA Flow
Chart

35. 1. https://www.fda.gov/drugs/abbreviated-new-drug-application-
anda/abbreviated-new-drug-application-anda-forms-and-submission-
requirements.
2. https://www.law.cornell.edu/cfr/text/21/314.50
3. https://www.fda.gov/drugs/types-applications/investigational-new-drug-
ind-application
4. https://www.slideshare.net.
5. Understanding FDA Regulatory Requirements for Investigational New
Drug Applications for Sponsor-Investigators.
6. Guarino Richard, A., (2009), “New Drug Approval Process” New York,
NY: Informa healthcare.
7. A Review On Drug Approval Process For US, Europe And India by
Vishal Prajapati, Rahulgiri Goswami.