This document provides an overview of Vineeth Kumar Ekbote's lab presentation on new drug applications (NDAs). The presentation covers what an NDA is, the goals and process of an NDA, the forms and contents required in an NDA submission, guidance documents for NDAs, and how NDAs are reviewed and approved by the FDA. The presentation also describes the various sections required in an NDA, including the application summary, chemistry and manufacturing controls, clinical data, and labeling.

1. LAB PRESENTATION
NEW DRUG APPLICATION
Presented by
Vineeth Kumar Ekbote
M.Pharm. (Ist semester)
Dept. Of Pharmaceutical Technology (Formulations)
NIPER, S.A.S. Nagar, Punjab.
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2. Flow of Presentation
• What is NDA
• Goals of NDA
• When will we go for NDA
• NDA Forms
• Contents of NDA
• Guidance document for submission of NDA
• Submission of NDA
• Review & Approval of NDA
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3. New Drug Application
 Since 1938, every new drug has been the subject of an
approved NDA before U.S. commercialization
 The NDA application is the vehicle through which drug sponsors
formally propose that the FDA approve a new pharmaceutical
for sale and marketing in the U.S.
 The data gathered during the animal studies and human clinical
trials of an Investigational New Drug (IND) become part of the
NDA
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4. Goals of NDA
• Safety and Effectiveness of a new drug in its proposed use(s)
• Whether the drug's proposed labeling (package insert) is appropriate
• Methods used in manufacturing the drug and the controls used to
maintain the drug's quality are adequate to preserve the drug's identity,
strength, quality, and purity
• The benefits of the drug outweigh the risks
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5. NDA
Pre Clinical
Clinical studies Filling
studies
I Phase-I Phase-II Phase-III
Animal N
testing of a D
New drug Safety
F
i Effective R
l ness E Approval
l
V
i
More Info. I
n
E
Short term g
W Disapproval
Long term
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6. NDA Forms & Electronic Submissions
• Form FDA- 356h. Application to market a New drug, biologic or an antibiotic
drug for human use
• Form FDA- 3397. User fee cover sheet
• Form FDA- 3331. New drug application field report
• Guidance documents for electronic submissions
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7. • Submit information regarding distributed Drug products an articles to
FDA, Which contains
(i) Any incident that causes the drug product or it’s labeling to be mistaken
for another article
(ii) Any bacteriological content/ chem. and physical detritioration/ failure to
meet the specification
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8. • The NDA may have as many as 20 different sections in addition to the Form
FDA-356h itself
• The specific contents of the NDA will depend on the Nature of the drug product
and the information available at the time of submission the application
• Form FDA-356h serves as Checklist as well as Certification that, the sponsor
agrees to comply with a range of legal and regulatory requirements
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9. Contd…
NDA Section 1 Index
NDA Section 2 Labeling
NDA Section 3 Application summary
NDA Section 4 Chemistry, Manufacturing, and Controls (CMC)
NDA Section 5
Nonclinical pharmacology and toxicology
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10. Contd…
NDA Section 6 Human pharmacokinetics and bioavailability
NDA Section 7 Clinical microbiology
NDA Section 8 Clinical data
NDA Section 9 Safety update reports
NDA Section 10 Statistics
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11. Contd…
NDA Section 11 Case report tabulations
NDA Section 12 Case Report Forms (CRFs)
NDA Section 13 Patent information
NDA Section 14 Patent certification
NDA Section 15 Establishment description
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12. Contd…
NDA Section 16 Debarment certificate
NDA Section 17 Field copy certification
NDA Section 18 User fee coversheet
NDA Section 19 Financial disclosure
NDA Section 20 Other
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13. Contd…
NDA Section 3: Application Summary :
• This is an abbreviated version of the entire application
• It should give reviewers a clear idea of the drug and its
application
• The summary usually comprises 50 to 200 pages
NDA Section 4: Chemistry, Manufacturing, andControls
(CMC) :
• The first technical section of the NDA It includes information
• The three main elements are
Chemistry, manufacturing and controls information
Samples (Submit only upon FDA’s request)
Methods validation package
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14. Contd…
CMC – Drug Substance
• The description
• The physical and chemical characteristics
• Structural elucidation
• Drug substance manufacturing methods
• Drug substance analytical controls
• Drug substance stability
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15. Contd…
CMC – Drug Product
• List of all components, quantities
• Drug product manufacturing methods
• Drug product packaging
• The drug product stability
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16. Contd…
NDA Section 7: Clinical Microbiology:
• Required for anti infective drug products
• Biochemical basis of the drug’s action on microbial
physiology
• The drug’s antimicrobial spectrum
• Mechanisms of resistance to the drug
• Clinical microbiology laboratory methods
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17. Contd…
NDA Section 11: Case Report Tabulations:
• Complete tabulations for each patient from Phase II and Phase
III efficacy study
• Phase I clinical pharmacology study
• Safety data from all clinical studies
NDA Section 12: Case Report Forms (CRFs):
• CRF for each patient who died during a clinical study
• Patients who were dropped from the study
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18. Guidance Documents for NDAs
• These documents are prepared for FDA review staff and applicants/sponsors
to provide guidelines to the processing, content, and evaluation/approval of
applications
• CDER gives guidance documents to help prepare NDAs
• CDER - Centre for Drug Evaluation and Research
Drug Registraion & Licensing System
ICSR-Individual Case Safety system Reporting
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19. Guidance Documents for NDAs
Contd…
• Bioavailability and bioequivalence studies for Orally administered drug products-
General considerations
• Formatting, assembling and sumitting new drug and antibiotic application
• Format and content of Chemistry, Manufacturing and Control section of an
application
• Format and content of Microbiology section of an application
• Format and content of Clinical and Statistical section of an application
• Container closure system for packing human drugs and biologics
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20. Guidance Documents for NDAs
Contd…
• Submitting documentation for the Stability of human drugs and biologics
• Format and content of human pharmacokinetics and bioavailability section of an
application
• Providing clinical evidence of effectiveness for human drug and biological
products
• NDAs- Impurities in drug substanses
• Drug Master Files (DMF)
• Required specifications for FDA’s IND, NDA and ANDA drug master file binders
• Refusal to file
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21. Common Technical Document
• In 1997 the FDA’s CDER, Published guidelines that allow sponsors to
submit NDAs electronically instead of on paper
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22. Specifications for FDA’s DMF binders
Polyethylene binders :
• Front- 248 X 292 mm
• Back- 248 X 305 mm
• Must be withstand at temp. of 150 degree C
• Ink colour must be BLACK
• FDA Form 2626 - Blue - NDA archival binder
• FDA Form 2675 - Red - IND archival binder
• FDA Form 3316 - Red - Drug master file binder
• FDA Form 3316a - Blue - Drug master file archival binder
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23. Specifications for FDA’s DMF binders
Paper binder :
• Front 267 X 292 mm
• Back 267 X 305 mm
• Ink colour must be BLCK, Maroon colour binder ink must be WHITE
• FDA Form 2626a - Red - NDA Chemistry binder
• FDA Form 2626b - Yellow - NDA Pharmacology binder
• FDA Form 2626c - Orange - NDA Pharmacokinetic binder
• FDA Form 2626d - White - NDA Microbiology binder
• FDA Form 2626e - Tan - NDA Clinical data binder
• FDA Form 2626f - Green - NDA Statistics binder
• FDA Form 2626h - Maroon - NDA Field submission chemistry binder
• FDA Form 2675a - Green - IND Chemistry binder
• FDA Form 2675b - Orange - IND Microbiology binder
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24. Assembling Applications for
Submission
The Review
The Archival Copy
Copy
FDA
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25. Archival Copy
• The cover letter
• Form FDA- 356h
• The Administrative sections
• Comprehensive NDA index
• Four copies of labeling section
• Three copies of CMC, Methods validation package
• Case report tabulations & Case report forms
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26. • The cover letter
• Form FDA- 356h
• The Administrative section
• Comprehensive NDA- index
• The labeling section
• The applicantion summary
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27. Applica
Applicant NDA -tion
Filable
No
Yes
Refuse to File
Letter is Issued Review by CDER
Medical Statistical
Biopharmaceutical Chemistry
Pharmacology Microbiology
Dis approval Approval
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28. FDA
Fast Track Approval Priority Review
Accelerated Approval
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29. Fast Track Approval
Drugs For
• Serious diseases
• Fill an unmet medical need
• Must be requested by the drug company
.
• FDA- 60 Days-Review- Decision
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30. Accelerated Approval
• In 1992 FDA instituted the Accelerated Approval regulation
• Based on a Surrogate endpoint, not on clinical outcome
• A surrogate endpoint is a marker- a laboratory measurement, or
physical sign - that is used in clinical trials as an indirect or substitute
measurement that represents a clinically meaningful outcome, such
as survival or symptom improvement
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31. • A Priority Review designation is given to drugs that offer major advances
in treatment
• The goal for completing a Priority Review is six months
• It can given for Drugs use to Serious/ Nonserious diseases
• Standard Review is applied to a drug that offers a most, only minor
improvement over existing marketed therapies (Ten months for Approval)
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