ANDA flowchart, INDA AND NDA REVIEW PROCESS, CASE STUDY, APPLICATION

1. Review Process of 505 b (1),
505 b(2), 505 (j) IN USA
Prepared By: Guided By:
Chandani Tripathi Dr. Gayatri Patel
17MPHRA010 Associate Professor
1

2. TABLE OF CONTENT
 INTRODUCTION
 21 CFR
 Organization of USFDA
 Organization of CDER
 Types of Application
 FDA Meetings
 RA Due Diligence
 PDUFA IN IND AND NDA REVIEW
PROCESS
 INDA AND NDA REVIEW PROCESS
 GDUFA IN ANDA REVIEW PROCESS
 ANDA REVIEW PROCESS
 SUMMARY
 REFERENCES
2

3. 3

4. INTRODUCTION
 Drugs play a vital role in modern day treatment strategies.
 The term ‘drug’ is derived for the French word “Drogue” that means
dry herb.
 FDA provides scientific and regulatory advice needed to bring new
therapies to market.
 Centers for Drug Evaluation and Research (CDER) supports the
pharmaceutical industry at every step in the process of innovation and
development of new drugs.
4
New Drug Approval Process, Richard Gaurino, Marcel Dekker INC, New York, 2nd Edition, Vol.56, 12-20.

5. USFDA
 It is an agency of the united states department of health and human services
(HHS)
 Its headquarter located at White Oak, Maryland
 The agency also has 223 field offices and13 laboratories located throughout
the 50 states of USA.
 FDA started opening office in foreign countries including China ,India , Costa
Rica , Chile , Belgium and UK.
5
Tabor MD E. Review of Pharmaceutical Competitive Intelligence for the Regulatory Affairs Professional. Drug Inf J [Internet].
2012;46(6):745–6.

6. 21 CFR (Code of Federal Regulation)
 USA—CODE OF FEDERAL REGULATIONS
 21---Pharmaceutical Only
 21 CFR Part 11 is the part of Title 21 of the Code of
Federal Regulations
 Establishes the United States Food and Drug
Administration (FDA) regulations on electronic records and
electronic signatures (ERES).
6Development & The US FDA. 2011;

7. 7
Laws, Regulations and Part in Code of Federal regulations
Sr. No. Regulation Part Purpose
1 21 CFR 312
Investigational New Drug
Application
2 21 CFR 314
INDA and NDA Applications for
FDA Approval to Market a New
Drug
3 21 CFR 316 Orphan Drugs
4 21 CFR 58
Good Lab Practice for Nonclinical
Laboratory [Animal] Studies.
7 21 CFR 201 Drug Labeling
9 21 CFR 320
Bioavailability and
Bioequivalence
10 21 CFR 310 New Drugs
New Drug Approval Process, Richard Gaurino, Marcel Dekker INC, New York, 2nd Edition, Vol.56, 189-212.

8. ORGANIZATION OF USFDA
8
Office of Commissioner
Center for Drug
evaluation and
Research
(CDER)
Center for
devices and
Radiological
Health
Center for
Vertinary
medicine
Cenetr for food
safety and
applied
Nutrition
Center for
toxicological
research
Administrative Law
Judge
Office of equal
opportunity and
management
Office of Health and
Science
Office of Regulatory
affairs
Office of
International
Activities
Office of management
www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnew
drugindapplication/default.html (D.O.A: 08-03-18)

9. TYPES OF APPLICATION
9
Investigational New Drug (IND) and New
Drug Application (NDA)
Abbreviated New Drug Application
(ANDA)
Over-the-Counter Drugs (OTC)
Biologic License Application (BLA)
Supplemental New Drug Application
(SNDA)
Services H, Information A, Description P. Food and Drug Administration APPLICATION TO MARKET A NEW OR
ABBREVIATED NEW. (910):7–9.

10. TYPES OF MEETING
1) Type A Meeting :
 Always within 30 days of a written meeting request.
 Is a meeting required to help an otherwise stalled product development
 E.g: To discuss clinical holds in which a response to hold issues has been
submitted.
2) Type B Meeting :
 within 60 days
 For concurrent development of a product for unrelated claims.
 E.g: (pre-IND) meetings (21 CFR 312.82)
 Certain end-of-phase 1 meetings (21 CFR 312.82)
10

11. 3) Type C Meeting :
 within 75 days
 Is a meeting between CBER or CDER and a sponsor or applicant regarding the
development and review of a product.
11
FDA. Guidance for Industry: Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants (draft).
2013;(910):1–14.

12. RA DUE DILIGENCE
 The process of investigating an investment or partnering opportunity to
mitigate risk is called as Due Diligence.
 The probability of success and a forecast of sales.
WHEN????
Performed prior to investing money in a deal or getting involved in a partnership
arrangement.
Special key team member-----To identify potential weaknesses that might
develop into deal-breaking problems.
12Ebel A. Due diligence of R&D Projects - a guideline for evaluating regulatory aspects. 2009;

13. Steps in RA Due Diligence:
1) Identify potential partner
2) Preliminary DD team members develop a forecast to generate discussion
around deal terms.
3) Agreement on the outline deal terms.
4) An information requirement list is sent to the potential partner.
5) A core due diligence team is assembled (external consultants can be utilized,
if necessary).
13

14. PDUFA (Prescription Drug User Fee Act )
 Passed in 1992
 To meet urgent patient demands for more timely approvals of life-saving
treatments and cures.
 To protect and promote the public health.
 PDUFA works to make review process easier more efficient.
ROLE ?????
 Enhanced the FDA’s access to tools, processes and expertise, with the latest
scientific advances.
 Helps in the development of new medicines to patients by providing scientific
and regulatory predictability.
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Services H, Information A, Description P. Food and Drug Administration APPLICATION TO MARKET A NEW OR ABBREVIATED
NEW. (910):7–9.

15. Bio pharmaceutical companies pay three different user fees under PDUFA:
15
Application fees: The initial fee when a
sponsor submits a New Drug Application (NDA)
or Biologics License Application (BLA) for the
first time.
Product fees: Annual fee for marketed drugs
for which no generic versions are approved.
Establishment fees: Final fee for each
manufacturing site that manufactures at least
one approved prescription drug for which no
generic versions are approved.
Services H, Information A, Description P. Food and Drug Administration APPLICATION TO MARKET A NEW OR ABBREVIATED
NEW. (910):7–9.

16. 505 b (1) & 505 b (2) Review Process
 505 b (1) is specially for ‘Investigational New Drug’ under 21 CFR
312.3 (b) (US FDA)
 After IND submission----- the sponsor must wait 30 days before
initiating any clinical trials.
 The studies in human can begin only after an IND is reviewed by the
FDA and “Local Institution Review Board” (IRB).
Review Team: The team composed of members of different
disciplines
(e.g., Medical Officer, Project manager,
Chemist, Pharmacologist,
Microbiologist Biopharmaceutical,
Statistician
16
Kaur J. Research Article US FDA Drug Approval Strategies for Pharmaceutical Industry. 2014;25(24):137–46.

17. 17
Applicant
Form---1571
IND
CDER REVIEW
Safety Review
Review Complete and
acceptable
No deficiences
Study Continue
NDAApplication
Notify deficiency to
applicant
Safety acceptable
to proceed
Chemical Hold
Decision
Notify applicant
Medicinal Chemistry
Pharmacological/
Toxicological
Statistical
NO
YES
NO
YES
NO

18. 18
Applicant
Form---356 h
NDA
Application Fillable
CDER REVIEW
Review complete and
acceptable
Labelling review
acceptable
Inspection of site
acceptable
Request for additional
information or revision
Acceptable
Further
Discussion for
Approval
satisfactory
results
pending
NDA
Approved
Medicinal Biopharmaceutical
Pharmacological/
Toxicological
Chemistry
Microbiological Statistical
Advisory Committee Meeting with
sponser
Refuse to
file the NDA
NO
YES
NO
YES
YES
NO
NO

19. The review copy is divided into six technical sections (“review sections”)
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Chemistry, Manufacturing and Controls (CMC) – RED.
Nonclinical Pharmacology and Toxicology – YELLOW.
Human Pharmacokinetics and Bioavailability – ORANGE.
Microbiology (if required) – WHITE.
Clinical Data –LIGHT BROWN.
Statistical – GREEN
Kaur J. Research Article US FDA Drug Approval Strategies for Pharmaceutical Industry. 2014;25(24):137–46.

20. GDUFA (Generic Drug User Fee Act)
 Law designed to speed access to safe and effective generic drugs to the
public, and reduce costs to industry.
 GDUFA is needed for the growth in generic drug applications
GDUF will focuses on three key aims:
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Access
Transparency
Safety
http://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM525236.pdf (D.O.A: 05-03-18)

21.  To keep coordination and integrity of the products.
 GDUFA applies for four types of fees:
21
1
•Application Fees: This is the first time fee, it is to be provided when
applying for the generic drug for the very first time to the FDA.
2
•DMF Fees: A DMF a one- time fee. The first time ANDA or DMF filled
after October 1, 2012, whether or not the DMF were reviewed prior to
GDUFA implementation.
3
•New ANDA Filing Fees: New application of ANDA filling after October 1,
2012.
4
•Backlog Fees: A one-time application fee for ANDAs that were pending
and had not received tentative approval prior to October 1, 2012.
Services H. ANDA Submissions – Prior Approval Supplements Under GDUFA Guidance for Industry ANDA Submissions — Prior Approval
Supplements Under GDUFA Guidance for Industry. 2017;(October).

22. 505 (j) Review Process
 505 (j) stands for Generic Drugs.
 Also known as “Abbreviated New Drug Application” (ANDA)
 It was introduced in 1984.
 On Friday, January 16, 2009, “Final rule” on the requirements for submission
of Bioequivalence Data was published in the Federal Register.
 21CFR Part 320 Bioavailability and Bioequivalence Requirements.
ANDA aims on the three areas:
1)Formulations and manufacturing,
2)container integrity and packaging, and
3) stability and expiration.
22
www.fda.gov/ForIndustry/UserFees/GenericDrugUserFees/default.htm (D.O.A: 09-03- 2018)

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Applicant
Form---
ANDA
Application Fillable
OGD/ CDER
REVIEW
Review complete of each
data
Bioequivalence
acceptable
Bioequivalence
deficiency letter
Chemical/Microbiological
results acceptable
Not approved
deficiency letter
Pre-approval
Inspection
Pending
Satisfactory
ResultsANDA
Approved
Bioequivalence
Review
Chemistry/Microbiological
Review
Pharmacological/
Toxicological Statistical
Advisory Committee Meeting with sponsor
Refuse to file the
NDA
NO
YES
YES
NONO
YES
NO
YES

24. SUMMARY
 The USFDA Drug Approval Strategies for Pharmaceutical Industries
communicate about the approval for drug products.
 It is necessary to understand the various steps for drug approval.
 FDA provides scientific and regulatory advice needed to bring new therapies
to market.
24

25. REFERENCES
 New Drug Approval Process, Richard Gaurino, Marcel Dekker INC, New York, 2nd
Edition, Vol.56, 189-212.
 www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandappro
ved/approvalapplications/abbreviatednewdrugapplicationandagenerics/default.ht
m(D.O.A:13-03-2018)
 www.fda.gov/ForIndustry/UserFees/GenericDrugUserFees/default.htm (D.O.A: 09-
03- 2018)
 Kaur J. Research Article US FDA Drug Approval Strategies for Pharmaceutical
Industry. 2014;25(24):137–46.
 FDA. Guidance for Industry: Formal Meetings Between the FDA and Biosimilar
Biological Product Sponsors or Applicants (draft). 2013;(910):1–14.
 Ebel A. Due deligence of R&D Projects - a guideline for evaluating regulatory
aspects. 2009;
 Services H. ANDA Submissions – Prior Approval Supplements Under GDUFA Guidance
for Industry ANDA Submissions — Prior Approval Supplements Under GDUFA
Guidance for Industry. 2017;(October).
 Services H, Information A, Description P. Food and Drug Administration
APPLICATION TO MARKET A NEW OR ABBREVIATED NEW. (910):7–9.
25

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