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CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 1
Vol Page
Regional Administrative Information .........................................................................................
1
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1.1
1.1.1
1.1.2
1.1.3
1.1.4
1.1.5
1.1.6
Forms .....................................................................................................................................................
FDA Form 1571 .................................................................................................... (not applicable)
FDA Form 356h ..............................................................................................................................
User Fee Cover Sheet (FDA Form 3397) .......................................................................................
Annual Report Transmittal Form (FDA Form 2252) ............................................ (not applicable)
Advertising and Promotional Labelling Form (FDA Form 2253) ......................... (not applicable)
Transmittal of Labels and Circulars (FDA Form 2567) ........................................ (not applicable)
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1.2
-
Cover Letter .........................................................................................................................................
Comprehensive Table of Contents for Modules 1 - 5 ............................................................................
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1.3
1.3.1
1.3.2
1.3.3
1.3.4
1.3.5
1.3.5.1
1.3.5.2
1.3.5.3
Administrative Information ...................................................................................................................
Contact/Sponsor Information ......................................................................................................
Field Copy Certification .................................................................................................................
Debarment Certification .................................................................................................................
Certification: Financial Interests and Arrangements of Clinical Investigators (FDA Form 3454) .
Patent & Exclusivity .......................................................................................................................
Patent Information (FDA Form 3542a) .................................................................................
Patent Certification ................................................................................................................
Statement of Claimed Exclusivity .........................................................................................
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1.4
1.4.1
1.4.2
1.4.3
1.4.4
References .............................................................................................................................................
Letters of Authorization ..................................................................................................................
Statement of Right of Reference ............................................................................ (not applicable)
List of Authorized Persons to Incorporate by Reference ....................................... (not applicable)
Cross Reference to Other Applications & Previously Submitted Information ................................
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1.5
1.5.1
1.5.2
1.5.3
1.5.4
1.5.5
1.5.6
1.5.7
1.5.8
Application Status ..................................................................................................................................
IND Withdrawal Request ................................................................................................................
Inactivation Request .......................................................................................................................
Reactivation Request ......................................................................................................................
Reinstatement Request ....................................................................................................................
Withdrawal of an Unapproved Application ....................................................................................
Withdrawal of a Listed Drug ..........................................................................................................
Request for Withdrawal of Application Approval ..........................................................................
Other Correspondence ....................................................................................................................
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CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 1
Vol Page
Regional Administrative Information (continued) .....................................................................
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1.6
1.6.1
1.6.2
1.6.3
Meetings .................................................................................................................................................
Meeting Request .............................................................................................................................
Meeting Background Materials.......................................................................................................
Correspondence Regarding Meetings .............................................................................................
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1.7
Fast Track ..................................................................................................................... (not applicable)
1.8
Special Protocol Assessment (SAP) Request ................................................................ (not applicable)
1.9
1.9.1
1.9.2
1.9.3
1.9.4
1.9.5
1.9.6
Pediatric Administrative Information .....................................................................................................
Request for Waiver ............................................................................................ (not applicable)
Request for Deferral .......................................................................................... (not applicable)
Request for Pediatric Exclusivity Determination ............................................ (not applicable)
Proposed Pediatric Study Request & Amendments ........................................ (not applicable)
Proposal for Written Agreement ...................................................................... (not applicable)
Other Correspondence Regarding Pediatric Exclusivity or Study Plans .........................................
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1.10
1.10.1
1.10.2
Dispute Resolutions ....................................................................................................... (not applicable)
Request for Dispute Resolution
Correspondence Relating to Dispute Resolution
1.11
1.11.1
1.11.2
1.11.3
Information Amendment (not covered under Modules 2 – 5)........................................ (not applicable)
Quality
Safety
Efficacy
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1.12
Other Correspondence ............................................................................................................................
1.12.1
Pre-IND Correspondence ................................................................................................................
1.12.2
Request to Charge .................................................................................................. (not applicable)
1.12.3
Notification of Charging Under Treatment IND .................................................... (not applicable)
1.12.4
Request for Comments and Advice on an IND ...............................................................................
1.12.5
Request for Waiver ................................................................................................ (not applicable)
1.12.6
Exemption from Informed Consent for Emergency Research ............................... (not applicable)
1.12.7
Public Disclosure Statement for Emergency Care Research .................................. (not applicable)
1.12.8
Correspondence Regarding Emergency Care Research ......................................... (not applicable)
1.12.9
Notification of Discontinuation of Clinical Trial ................................................... (not applicable)
1.12.10
Generic Drug Enforcement Act (GDEA) Statement ..................................................................
1.12.11
Basis for Submission Statement ......................................................................................................
1.12.12
Comparison of Generic Drug and Reference Listed Drug (RLD) ...................................................
1.12.13
Request for Waiver of in vivo Studies.............................................................................................
1.12.14
Environmental Impact Analysis Statement .....................................................................................
1.12.15
Request for Waiver of in vivo Bioavailability Studies ................................................................
1.12.16
Field Alert Reports ................................................................................................ (not applicable)
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Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 1
Vol Page
Regional Administrative Information (continued) .....................................................................
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1.14
Labelling .................................................................................................................................................
1.14.1
Draft Labelling................................................................................................................................
1.14.1.1
Draft Carton & Container Labels ...........................................................................................
1.14.1.2
Annotated Draft Labelling Text .........................................................................................
1.14.1.3
Draft Labelling Text ..............................................................................................................
1.14.1.4
Label Comprehension Studies ..................................................................... (not applicable)
1.14.1.5
Labelling History ...................................................................................................................
1.14.2
Final Labelling ................................................................................................................................
1.14.2.1
Final Carton & Container Labels ...........................................................................................
1.14.2.2
Final Package Inserts .............................................................................................................
1.14.2.3
Final Labelling Text ..............................................................................................................
1.14.3
Listed Drug Labelling .....................................................................................................................
1.14.3.1
Annotated Comparison with Listed Drug..........................................................................
1.14.3.2
Approved Labelling Text for Listed Drug .............................................................................
1.14.3.3
Labelling Text for Reference Listed Drug .............................................................................
1.14.4
Investigational Drug Labelling .......................................................................................................
1.14.4.1
Investigator’s Brochure .........................................................................................................
1.14.4.2
Investigational Drug Labelling ..............................................................................................
1.14.4.3
FILL IN ................................................................................................................................
1.14.4.4
FILL IN ................................................................................................................................
1.14.4.5
Foreign Labelling ......................................................................................... (not applicable)
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Promotional Material ..............................................................................................................................
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Risk Management Plans .........................................................................................................................
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Annual Reports .............................................................................................................. (not applicable)
1.13.1
Summary for Non-Clinical Studies
1.13.2
Summary of Clinical Pharmacology Studies
1.13.3
Summary of Safety Information
1.13.4
Summary of Labelling Changes
1.13.5
Summary of Manufacturing Changes
1.13.6
Summary of Microbiological Changes
1.13.7
Summary of Other Significant New Information
1.13.8
Individual Study Information
1.13.9
General Investigational Plan
1.13.10
Foreign Marketing History
1.13.11
Distribution Data
1.13.12
Status of Post-Marketing Commitments
1.13.13
Status of Other Post-Marketing Studies
1.13.14
Log of Outstanding Regulatory Business
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[CLIENT NAME]
NDA [##,###]
[PRODUCT NAME, STRENGTH[
CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 2
Vol Page
Common Technical Document Summaries.................................................................................
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Comprehensive Table of Contents for Module 2 ................................................................................
1
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2.2
Introduction ..........................................................................................................................................
1
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2.3
2.3.S
2.3.S.1
2.3.S.2
2.3.S.3
2.3.S.4
2.3.S.5
2.3.S.6
2.3.S.7
2.3.P
2.3.P.1
2.3.P.2
2.3.P.3
2.3.P.4
2.3.P.5
2.3.P.6
2.3.P.7
2.3.P.8
2.3.A
2.3.A.1
2.3.A.2
2.3.A.3
2.3.R
Quality Summary ....................................................................................................................................
Drug Substance ...............................................................................................................................
General Information...............................................................................................................
Manufacture ...........................................................................................................................
Characterization .....................................................................................................................
Control of Drug Substance ....................................................................................................
Reference Standards or Materials ..........................................................................................
Container/Closure System .....................................................................................................
Stability .................................................................................................................................
Drug Product...................................................................................................................................
Description and Composition of the Drug Product ................................................................
Pharmaceutical Development ................................................................................................
Manufacture ...........................................................................................................................
Control of Excipients .............................................................................................................
Control of Drug Product ........................................................................................................
Reference Standards or Materials ..........................................................................................
Container/Closure System .....................................................................................................
Stability .................................................................................................................................
Appendices .....................................................................................................................................
Facilities and Equipment .......................................................................................................
Adventitious Agents Safety Evaluation .................................................................................
Novel Excipients....................................................................................................................
Regional Information ......................................................................................................................
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2.4
2.4.1
2.4.2
2.4.3
2.4.4
2.4.5
2.4.6
Nonclinical Overview .............................................................................................................................
Overview of the Nonclinical Testing Strategy ................................................................................
Pharmacology .................................................................................................................................
Pharmacokinetics ............................................................................................................................
Toxicology ......................................................................................................................................
Integrated Overview and Conclusions ............................................................................................
List of Literature Citations ..............................................................................................................
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2.5
2.5.1
2.5.2
2.5.3
2.5.4
2.5.5
2.5.6
2.5.7
Clinical Overview .................................................................................................................................
Product Development Rationale .....................................................................................................
Overview of Biopharmaceutics .......................................................................................................
Overview of Clinical Pharmacology ...............................................................................................
Overview of Efficacy ......................................................................................................................
Overview of Safety .........................................................................................................................
Benefits and Risks Conclusions ......................................................................................................
References ......................................................................................................................................
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Module 1 – Overall Table of Contents
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Module Description
Module 2
Vol Page
Common Technical Document Summaries (continued) ............................................................
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2.6
Nonclinical Written and Tabulated Summaries ......................................................................................
2.6.1
Introduction ....................................................................................................................................
2.6.2
Pharmacology Written Summary ....................................................................................................
2.6.2.1
Brief Summary ......................................................................................................................
2.6.2.2
Primary Pharmacodynamics ..................................................................................................
2.6.2.3
Secondary Pharmacodynamics ..............................................................................................
2.6.2.4
Safety Pharmacology .............................................................................................................
2.6.2.5
Pharmacodynamic Drug Interactions .....................................................................................
2.6.2.6
Discussion and Conclusions ..................................................................................................
2.6.2.7
Tables and Figures .................................................................................................................
2.6.3
Pharmacology Tabulated Summary ................................................................................................
2.6.4
Pharmacokinetics Written Summary ..............................................................................................
2.6.4.1
Brief Summary ......................................................................................................................
2.6.4.2
Methods of Analysis ..............................................................................................................
2.6.4.3
Absorption .............................................................................................................................
2.6.4.4
Distribution ............................................................................................................................
2.6.4.5
Metabolism (interspecies comparison) ..................................................................................
2.6.4.6
Excretion ...............................................................................................................................
2.6.4.7
Pharmacokinetic Drug Interactions........................................................................................
2.6.4.8
Other Pharmacokinetic Studies ..............................................................................................
2.6.4.9
Discussion and Conclusions ..................................................................................................
2.6.4.10
Tables and Figures .................................................................................................................
2.6.5
Pharmacokinetics Tabulated Summary ...........................................................................................
2.6.6
Toxicology Written Summary ........................................................................................................
2.6.6.1
Brief Summary ......................................................................................................................
2.6.6.2
Single-Dose Toxicity .............................................................................................................
2.6.6.3
Repeat-Dose Toxicity ............................................................................................................
2.6.6.4
Genotoxicity ..........................................................................................................................
2.6.6.5
Carcinogenicity......................................................................................................................
2.6.6.6
Reproductive and Developmental Toxicity ...........................................................................
2.6.6.7
Local Tolerance .....................................................................................................................
2.6.6.8
Other Toxicity Studies (if available) ......................................................................................
2.6.6.9
Discussion and Conclusions ..................................................................................................
2.6.6.10
References .............................................................................................................................
2.6.7
Toxicology Tabulated Summary .....................................................................................................
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Module 1 – Overall Table of Contents
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Module Description
Module 2
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Common Technical Document Summaries (continued) ............................................................
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Clinical Summary .................................................................................................................................
2.7.1
Summary of Biopharmaceutic and Associated Analytical Methods ...............................................
2.7.1.1
Background and Overview ................................................................................................
2.7.1.2
Summary of Results of Individual Studies ........................................................................
2.7.1.3
Comparison and Analyses of Results Across Studies ........................................................
2.7.1.4
Appendix ...........................................................................................................................
2.7.2
Summary of Clinical Pharmacology Studies ..................................................................................
2.7.2.1
Background and Overview ................................................................................................
2.7.2.2
Summary of Results of Individual Studies ........................................................................
2.7.2.3
Comparison and Analyses of Results Across Studies ........................................................
2.7.2.4
Special Studies...................................................................................................................
2.7.2.5
Appendix ...........................................................................................................................
2.7.3
Summary of Clinical Efficacy ........................................................................................................
2.7.3.1
Background and Overview of Clinical Efficacy ................................................................
2.7.3.2
Summary of Results of Individual Studies ........................................................................
2.7.3.3
Comparison and Analyses of Results Across Studies ........................................................
2.7.3.3.1
Study Populations ......................................................................................................
2.7.3.3.2
Comparison of Efficacy Results Across All Studies .................................................
2.7.3.3.3
Comparison of Results in Sub-Populations ...............................................................
2.7.3.4
Analysis of Clinical Information Relevant to Dosing Recommendations .........................
2.7.3.5
Persistence of Efficacy and/or Tolerance Effects ..............................................................
2.7.3.6
Appendix ...........................................................................................................................
2.7.4
Summary of Clinical Safety ............................................................................................................
2.7.4.1
Exposure to the Drug .........................................................................................................
2.7.4.1.1
Overall Safety Evaluation Plan and Narratives of Safety Studies .............................
2.7.4.1.2
Overall Extent of Exposure .......................................................................................
2.7.4.1.3
Demographic and Other Characteristics of Study Population ...................................
2.7.4.2
Adverse Events ..................................................................................................................
2.7.4.2.1
Analysis of Adverse Events by Organ System or Syndrome .....................................
2.7.4.2.2
Narratives ..................................................................................................................
2.7.4.2.3
Deaths........................................................................................................................
2.7.4.2.4
Other Serious Adverse Events ...................................................................................
2.7.4.3
Clinical Laboratory Evaluations ........................................................................................
2.7.4.4
Vital Signs, Physical Findings, Observations Related to Safety ........................................
2.7.4.5
Safety in Special Groups and Situations ............................................................................
2.7.4.5.1
Intrinsic Factors .........................................................................................................
2.7.4.5.2
Extrinsic Factors ........................................................................................................
2.7.4.5.3
Drug Interactions .......................................................................................................
2.7.4.5.4
Use in Pregnancy and Lactation ................................................................................
2.7.4.5.5
Overdose ...................................................................................................................
2.7.4.5.6
Drug Abuse ...............................................................................................................
2.7.4.5.7
Withdrawal and Rebound ..........................................................................................
2.7.4.5.8
Effects on Ability to Drive or Operate Machinery or Impairment of Mental Ability
2.7.4.6
Post-Marketing Data ..........................................................................................................
2.7.4.7
Appendix ...........................................................................................................................
2.7.5
References ......................................................................................................................................
2.7.6
Synopses of Individual Studies .......................................................................................................
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CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 3
Vol Page
Quality ...........................................................................................................................................
2
x
3.1
Comprehensive Table of Contents for Module 3 ...................................................................................
3.2
Drug Substance ......................................................................................................................................
3.2.S.1
General Information .......................................................................................................................
3.2.S.1.1
Nomenclature ....................................................................................................................
3.2.S.1.2
Structure ............................................................................................................................
3.2.S.1.3
General Properties .............................................................................................................
3.2.S.2
Manufacture ...................................................................................................................................
3.2.S.2.1
Manufacturer(s) .................................................................................................................
3.2.S.2.2
Description of Process and Process Controls .....................................................................
3.2.S.2.3
Control of Materials...........................................................................................................
3.2.S.2.4
Control of Critical Steps and Intermediates .......................................................................
3.2.S.2.5
Process Validation and/or Evaluation ................................................................................
3.2.S.3
Characterization .............................................................................................................................
3.2.S.3.1
Elucidation of Structure and Other Characteristics ............................................................
3.2.S.3.2
Impurities...........................................................................................................................
3.2.S.4
Control of Drug Substance.............................................................................................................
3.2.S.4.1
Specifications ....................................................................................................................
3.2.S.4.2
Analytical Procedures ........................................................................................................
3.2.S.4.3
Validation of Analytical Procedures ..................................................................................
3.2.S.4.4
Batch Analyses ..................................................................................................................
3.2.S.4.5
Justification of Specification .............................................................................................
3.2.S.5
Reference Standards or Materials ..................................................................................................
3.2.S.6
Container/Closure Systems ............................................................................................................
3.2.S.7
Stability..........................................................................................................................................
3.2.S.7.1
Stability Summary and Conclusions ..................................................................................
3.2.S.7.2
Post-approval Stability Protocol and Commitment............................................................
3.2.S.7.3
Stability Data .....................................................................................................................
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3.2.P
Drug Product ..........................................................................................................................................
3.2.P.1
Description and Composition of the Drug Product ........................................................................
3.2.P.2
Pharmaceutical Development ........................................................................................................
3.2.P.2.1
Composition of Drug Product ............................................................................................
3.2.P.2.2
Formulation, Overages, Properties ....................................................................................
3.2.P.2.3
Manufacturing Process Development ................................................................................
3.2.P.2.4
Container/Closure System .................................................................................................
3.2.P.2.5
Microbiological Attributes.................................................................................................
3.2.P.2.6
Compatibility .....................................................................................................................
3.2.P.3
Manufacture ...................................................................................................................................
3.2.P.3.1
Manufacturer(s) .................................................................................................................
3.2.P.3.2
Batch Formula ...................................................................................................................
3.2.P.3.3
Description of Manufacturing Process and Process Controls ............................................
3.2.P.3.4
Controls of Critical Steps and Intermediates .....................................................................
3.2.P.3.5
Process Validation and/or Evaluation ................................................................................
3.2.P.4
Control of Excipients .....................................................................................................................
3.2.P.4.1
Specifications ....................................................................................................................
3.2.P.4.2
Analytical Procedures ........................................................................................................
3.2.P.4.3
Validation of Analytical Procedures ..................................................................................
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Overall CTD Table of Contents
Module Description
3.2.P.4.4
3.2.P.4.5
3.2.P.4.6
3.2.P.5
3.2.P.5.1
3.2.P.5.2
3.2.P.5.3
3.2.P.5.4
3.2.P.5.5
3.2.P.5.6
3.2.P.6
3.2.P.7
3.2.P.8
3.2.P.8.1
3.2.P.8.2
3.2.P.8.3
Vol Page
Justification of Specifications ............................................................................................
Excipients of Human or Animal Origin .............................................................................
Novel Excipients ...............................................................................................................
Control of Drug Product ................................................................................................................
Specifications ....................................................................................................................
Analytical Procedures ........................................................................................................
Validation of Analytical Procedures ..................................................................................
Batch Analyses ..................................................................................................................
Characterization of Impurities ...........................................................................................
Justification of Specifications ............................................................................................
Reference Standards or Materials ..................................................................................................
Container/Closure System .............................................................................................................
Stability..........................................................................................................................................
Stability Summary and Conclusions ..................................................................................
Post-Approval Stability Protocol and Stability Commitments ...........................................
Stability Data .....................................................................................................................
3
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3.2.A
3.2.A.1
3.2.A.2
3.2.A.3
Appendices.............................................................................................................................................
Facilities and Equipment................................................................................................................
Adventitious Agents Safety Evaluation .........................................................................................
Novel Excipients ............................................................................................................................
4
4
4
4
x
x
x
x
3.2.R
3.2.R.1
4
x
3.2.R.2
Regional Information .............................................................................................................................
Batch Records
Lot #### (STRENGTH) ...............................................................................................................
Lot #### (STRENGTH) ...............................................................................................................
Methods Validation Packet ............................................................................................................
4
5
5
x
x
x
3.3
Key Literature References ......................................................................................................................
5
x
8
[CLIENT NAME]
NDA [##,###]
[PRODUCT NAME, STRENGTH[
CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 4
Vol Page
Non-Clinical Study Reports .........................................................................................................
6
x
4.1
Comprehensive Table of Contents for Module 4 ....................................................................................
4.2
Study Reports .........................................................................................................................................
4.2.1
Pharmacology .................................................................................................................................
4.2.1.1
Primary Pharmacodynamics ..................................................................................................
4.2.1.2
Secondary Pharmacodynamics ..............................................................................................
4.2.1.3
Safety Pharmacology .............................................................................................................
4.2.1.4
Pharmacodynamic Drug Interactions .....................................................................................
4.2.2
Pharmacokinetics ............................................................................................................................
4.2.2.1
Analytical Methods and Validation Reports ..........................................................................
4.2.2.2
Absorption .............................................................................................................................
4.2.2.3
Distribution ............................................................................................................................
4.2.2.4
Metabolism ............................................................................................................................
4.2.2.5
Excretion ...............................................................................................................................
4.2.2.6
Pharmacokinetic Drug Interactions........................................................................................
4.2.2.7
Other Pharmacokinetic Studies ..............................................................................................
4.2.3
Toxicology ......................................................................................................................................
4.2.3.1
Single-Dose Toxicity .............................................................................................................
4.2.3.2
Repeat-Dose Toxicity ............................................................................................................
4.2.3.3
Genotoxicity ..........................................................................................................................
4.2.3.3.1
In vitro Studies ..........................................................................................................
4.2.3.3.2
In vivo Studies ...........................................................................................................
4.2.3.4
Carcinogenicity......................................................................................................................
4.2.3.5
Reproductive and Development Toxicity ..............................................................................
4.2.3.5.1
Fertility and Embryonic Development ......................................................................
4.2.3.5.2
Embryo-Fetal Development ......................................................................................
4.2.3.5.3
Pre- and Post-natal Development & Maternal Function ............................................
4.2.3.5.4
Offspring, Juvenile, Second & Third-Generation Studies .........................................
4.2.3.6
Local Tolerance .....................................................................................................................
4.2.3.7
Other Toxicity Studies ...........................................................................................................
4.2.3.7.1
Antigenicity ...............................................................................................................
4.2.3.7.2
Immunogenicity ........................................................................................................
4.2.3.7.3
Mechanistic Studies (not included elsewhere) ...........................................................
4.2.3.7.4
Dependence ...............................................................................................................
4.2.3.7.5
Metabolites ................................................................................................................
4.2.3.7.6
Impurities ..................................................................................................................
4.2.3.7.7
Other..........................................................................................................................
4.3
Literature References ..............................................................................................................................
6
6
6
6
6
6
6
6
6
6
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9
[CLIENT NAME]
NDA [##,###]
[PRODUCT NAME, STRENGTH[
CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Module 5
Vol Page
Clinical Study Reports ..................................................................................................................
7
x
5.1
Comprehensive Table of Contents for Module 5 ....................................................................................
7
x
5.2
Tabular Listing of All Clinical Studies ...................................................................................................
7
x
5.2.1
CLIENT Studies ............................................................................................................................
7
x
5.2.2
Tabular Listing of Clinical Investigators ........................................................................................
7
x
Clinical Study Reports ............................................................................................................................
7
x
Reports of Biopharmaceutic Studies ...............................................................................................
7
x
Bioavailability (BA) Study Reports .......................................................................................
7
x
CLIENT Studies .......................................................................................................
7
x
 Protocol #### (Food-Effect) ............................................................................
7
x
 Protocol #### (Food-Effect) (continued) .........................................................
8
x
 Protocol #### (Food-Effect) (continued) .........................................................
9
x
 Protocol #### (Food-Effect) (continued) .........................................................
10
x
REFERENCE LISTED DRUG SPONSOR STUDIES.........................................
10
x
5.3
5.3.1
5.3.1.1
5.3.1.1.1
5.3.1.1.2
 Fill in data from NDA Summary Basis of Approval Review ......................
.................................................................................................................. 10
.................................................................................................................... x
5.3.1.1.3
Published Studies ......................................................................................................
10
x
5.3.1.1.4
Summary ...................................................................................................................
10
x
Comparative BA & BE Study Reports ..................................................................................
11
x
CLIENT Studies .......................................................................................................
11
1
 Protocol #### ..................................................................................................
11
8
 Appendices 16.0 ................................................................................................
11
40
 Appendices 16.1 – Study Information ...............................................................
11
40
 Appendices 16.1.1 – Protocol & IRB Approval ................................................
11
40
 Appendices 16.1.2 – Sample Case Report Form (CRF) ....................................
11
58
 Appendices 16.1.3 – IRB Membership Roster ..................................................
11
69
 Appendices 16.1.4 – List of Investigators .........................................................
11
78
 Appendices 16.1.5 – Signature Page .................................................................
11
113
 Appendices 16.1.6 – Table of Dosing Dates and Times ....................................
11
114
 Appendices 16.1.7 – Randomization Scheme and Codes ..................................
11
123
 Appendices 16.1.8 – Audit Certificate ..............................................................
11
124
 Appendices 16.1.9 – Statistical Report..............................................................
11
125
 Protocol #### (continued) ..............................................................................
12
 Appendices 16.1.9 – Statistical Report (continued) ..........................................
12
1
 Appendices 16.1.10 – Analytical Report ...........................................................
12
132
 Addendum to Method Validation Report ..........................................................
12
200
5.3.1.2
5.3.1.2.1
10
[CLIENT NAME]
NDA [##,###]
[PRODUCT NAME, STRENGTH[
CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Vol Page
 Protocol #### (continued) ..............................................................................
13
 Appendices 16.1.10 – Analytical Report (continued)........................................
13
1
 Appendix 16.1.11 – Publications Based on this Study (NA) .............................
13
-
 Appendix 16.1.12 – Publications Referenced in Report (NA) ..........................
13
-
 Appendix 16.2 – Subject Data Listings .............................................................
13
419
 Appendix 16.2.1 – Discontinued Subjects.........................................................
13
419
 Appendix 16.2.2 – Protocol Deviations (none) .................................................
13
-
 Appendix 16.2.3 – Concomitant Medications ...................................................
13
421
 Appendix 16.2.4 – Subject Demographics ........................................................
13
422
 Appendix 16.2.5 – Table of Deviations from Scheduled Collections................
13
425
 Appendix 16.2.6 – Individual Efficacy Response (NA) ....................................
13
-
 Appendix 16.2.7 – Adverse Event Listings .......................................................
13
426
 Appendix 16.2.8 – Listing of Individual Lab Measurements ((NA)..................
13
-
 Appendix 16.3 – Case Report Forms (CRF) (Subjects 1 – 44)..........................
13
-
 Appendix 16.3.1 – CRFs for Deaths, Serious AE, & Discontinuations.............
17
XX
 Appendix 16.3.2 – Other CRFs Submitted (NA) ..............................................
13
-
 Appendix 16.4 – Individual Patient Listings .....................................................
17
XX
 Protocol #### .................................................................................................
14
 Protocol #### ..................................................................................................
14
1
 Appendices 16.0 ................................................................................................
14
80
 Appendices 16.1 – Study Information ...............................................................
14
80
 Appendices 16.1.1 – Protocol & Protocol Amendments ...................................
14
81
 Appendices 16.1.2 – Sample Case Report Form (CRF) ....................................
14
187
 Appendices 16.1.3 – IRB Membership & Sample Informed Consent ...............
14
219
 Appendices 16.1.4 – List of Investigators .........................................................
14
270
 Appendices 16.1.5 – Signature Page .................................................................
14
278
Multiple Batches (NA) ......................................................................................
14
-
 Appendices 16.1.7 – Randomization Scheme and Codes ..................................
14
281
 Appendices 16.1.8 – Audit Certificate (NA) .....................................................
14
-
14
285
Standardization Methods and QA Procedures ...................................................
14
304
 Appendix 16.1.11 – Publications Based on this Study (NA) .............................
14
320
 Appendix 16.1.12 – Publications Referenced in Report (NA) ..........................
14
321
 Appendices 16.1.6 – List of Subjects Receiving Test Drugs from
 Appendices 16.1.9 – Documentation of Pharmacokinetic and
Statistical Methods ............................................................................................
 Appendices 16.1.10 – Documentation of Inter-Laboratory
11
[CLIENT NAME]
NDA [##,###]
[PRODUCT NAME, STRENGTH[
CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
Vol Page
 Protocol #### (continued) ..............................................................................
15
 Appendix 16.2 – Subject Data Listings .............................................................
15
2
 Appendix 16.2.1 – Discontinued Subjects (none) .............................................
15
3
 Appendix 16.2.2 – Protocol Deviations – Blood Samples.................................
15
5
 Appendix 16.2.3 – Subjects Excluded from Analysis (none) ............................
15
7
 Appendix 16.2.4 – Demographic Data & Baseline Characteristics ...................
15
9
 Appendix 16.2.5 – Drug Concentration Data ....................................................
15
12
 Appendix 16.2.6 – Individual Data ...................................................................
15
48
 Appendix 16.2.7 – Adverse Event Listings .......................................................
15
93
 Appendix 16.2.8 – Listing of Individual Lab Measurements ............................
15
103
 Appendix 16.2.9 – Statistical Analysis..............................................................
15
177
 Appendix 16.3 – Case Report Forms (CRF) .....................................................
15
196
Withdrawals for AE (none) ...............................................................................
15
196
 Appendix 16.3.2 – Other CRFs Submitted (NA) ..............................................
15
198
 Appendix 16.4 – Individual Subject Data Listings ............................................
15
199
 Appendix 16.5 – Analytical Report ...................................................................
15
200
 Appendix 16.6 – Validation Report ..................................................................
15
365
REFERENCE LISTED DRUG SPONSOR STUDIES.........................................
16
x
 FILL IN AS NEEDED: Summary Basis of Approval Review .......................
16
x
 FILL IN AS NEEDED: Summary Basis of Approval Review .......................
16
x
 Appendix 16.3.1 – CRFs for Deaths, Other Serious Adverse Events, &
5.3.1.2.2
 FILL IN AS NEEDED: Summary Basis of Approval Review .......................
16
x
5.3.1.2.3
Published Studies ......................................................................................................
16
x
5.3.1.2.4
Summary ...................................................................................................................
16
x
5.3.1.3
In vitro/In vivo Correlation (IV/IVC).....................................................................................
16
x
5.3.1.4
Bioanalytical and Analytical Methods ...................................................................................
16
x
5.3.2
Reports of Studies Pertinent to Human PK .....................................................................................
16
x
5.3.2.1
Plasma Protein Binding Study Reports ..................................................................................
16
x
5.3.2.2
Hepatic Metabolism/Drug Interactions ..................................................................................
16
x
5.3.2.3
Studies Using other Human Materials ...................................................................................
16
x
Reports of Human PK Studies ........................................................................................................
16
x
5.3.3.1
Healthy Subject PK and Tolerability .....................................................................................
16
x
5.3.3.2
Patient PK and Initial Tolerability .........................................................................................
16
x
5.3.3.3
Intrinsic Factor PK.................................................................................................................
16
x
5.3.3.4
Extrinsic Factor PK ...............................................................................................................
16
x
5.3.3
5.3.3.5
Population PK ........................................................................................................................
16
x
Reports of Human PD Studies .......................................................................................................
16
x
5.3.4.1
Healthy Subject PD and PK/PD Studies ................................................................................
16
x
5.3.4.2
Patient PD and PK/PD ...........................................................................................................
16
x
5.3.4
12
[CLIENT NAME]
NDA [##,###]
[PRODUCT NAME, STRENGTH[
CONFIDENTIAL
Module 1 – Overall Table of Contents
Overall CTD Table of Contents
Module Description
5.3.5
Vol Page
Reports of Efficacy and Safety Studies ...........................................................................................
16
x
Controlled Clinical Studies on Indication ..............................................................................
16
x
INDICATION # 1 .....................................................................................................
16
x
5.3.5.1.A.1
CLIENT Studies...............................................................................................
16
x
5.3.5.1.A.2
NDA ##,### Sponsor Studies ...........................................................................
16
x
5.3.5.1.A.3
Published Studies ..............................................................................................
16
x
5.3.5.1.A.4
Summary ...........................................................................................................
16
x
5.3.5.3.1.B
INDICATION # 2 .....................................................................................................
16
x
5.3.5.1.B.1
CLIENT Studies...............................................................................................
16
x
5.3.5.1.B.2
NDA ##,### Sponsor Studies ...........................................................................
16
x
5.3.5.1.B.3
Published Studies ..............................................................................................
16
x
5.3.5.1
5.3.5.1.A
5.3.5.1.B.4
Summary ...........................................................................................................
16
x
Uncontrolled Clinical Studies ................................................................................................
16
x
5.3.5.2.1
CLIENT Studies .......................................................................................................
16
x
5.3.5.2.2
NDA ##,### Sponsor Studies....................................................................................
16
x
 Summary Basis of Approval: Clinical Review .................................................
16
x
5.3.5.2.3
Published Studies ......................................................................................................
16
x
5.3.5.2.4
Summary ...................................................................................................................
16
x
Reports of Analyses of Data from More than One Study ......................................................
16
x
5.3.5.3.1
Integrated Summary of Safety ...................................................................................
16
x
5.3.5.3.1.A
INDICATION # 1 .....................................................................................................
16
x
5.3.5.3.1.B
INDICATION # 2 .....................................................................................................
16
x
5.3.5.3.2
Integrated Summary of Efficacy................................................................................
16
x
 INDICATION # 1 .............................................................................................
16
x
 INDICATION # 2 .............................................................................................
16
x
Other Clinical Study Reports .................................................................................................
17
x
Reports of Post-Marketing Experience ...........................................................................................
17
x
5.3.6.1
Regulatory History of NDA ##,### .......................................................................................
17
x
5.3.6.2
Generic Approvals .................................................................................................................
17
x
5.3.6.3
Safety Data from Post-Marketing Surveillance .....................................................................
17
x
5.3.6.3.1
Foreign Marketing Data in Support of the Original NDA .........................................
17
x
5.3.6.3.2
US Post-Marketing Surveillance Data .......................................................................
17
x
5.3.5.2
5.3.5.3
5.3.5.4
5.3.6
5.3.7
Case Report Forms (CRF)/Individual Patient Listings ...................................................................
17
x
5.3.7.1
Protocol ##### – BE Study ...................................................................................................
17
x
5.3.7.2
Protocol ##### – Food-Effect Study .....................................................................................
17
x
Literature References ..............................................................................................................................
18
x
Literature References (continued) ..........................................................................................................
19
x
5.4
13