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The Comprehensive Table of Contents Headings and Hierarchy
Revision History
Date Version Summary of Changes 2004-07 1.0 Original version 2005-06-16 1.1 Corrections and additions to the mapping tables 2005-07-06 1.2 Corrections to the headings 2012-06-01 2.0 Corrections and additions to the mapping tables based on major update to Module 1 specifications (Summary of Changes in Section C of Appendix 2) 2012-11-01 2.1 Modified the heading for 1.16 and added REMS and non-REMS sub-headings (Summary of Changes in Section B of Appendix 2) 2013-08-23 2.2 Added two new attributes for 1.15.2.1 (Summary of Changes in Section A of Appendix 2) 2014-02-07 2.3 Modified the heading for 1.15.1.5 (Summary of Changes in Section A of Appendix 2) 2017-04-17 2.3.1 Updated heading names under sections 4.2.1.1, 5.3.1.1, 5.3.5.3 to align with file tags in ICH valid values version 3.0. 2018-11-01 2.3.2 Fixed page numbering and updated content under sections 5.3.5. and 5.3.5. 2020-11-09 2.3.3 Added file tags under sections 4.2.1.1, 5.3.1.1, and 5.3.5.4 to align with file tags in ICH valid values version 5.0.
Version 2.3. 3 ii
- The Comprehensive Table of Contents Headings and Hierarchy Table of Contents
- Module 1 Administrative information
- Module 2 Summaries
- Module 3 Quality
- Module 4 Nonclinical Study Reports
- Module 5 Clinical Study Reports
- Appendix 1 – Mapping Section...................................................................................................
- Appendix 2 – Module 1 Summary of Changes .............................................................................
- A. Module 1 Summary of Changes (02/07/2014, version 2.3).........................................................
- B. Module 1 Summary of Changes (08/23/2013, version 2.2).........................................................
- C. Module 1 Summary of Changes (11/1/2012, version 2.1)...........................................................
- D. Module 1 Summary of Changes (6/1/2012, version 2.0) ............................................................
1.8 Special protocol assessment request 1.8.1 Clinical study 1.8.2 Carcinogenicity study 1.8.3 Stability study 1.8.4 Animal efficacy study for approval under the animal rule 1.9 Pediatric administrative information 1.9.1 Request for waiver of pediatric studies 1.9.2 Request for deferral of pediatric studies 1.9.3 Request for pediatric exclusivity determination 1.9.4 Proposed pediatric study request and amendments 1.9.5 Proposal for written agreement ( no longer applicable ) 1.9.6 Other correspondence regarding pediatric exclusivity or study plans 1.10 Dispute resolution 1.10.1 Request for dispute resolution 1.10.2 Correspondence related to dispute resolution 1.11 Information amendment: Information not covered under modules 2 to 5 1.11.1 Quality information amendment 1.11.2 Nonclinical information amendment 1.11.3 Clinical information amendment 1.11.4 Multiple module information amendment 1.12 Other correspondence 1.12.1 Pre IND correspondence 1.12.2 Request to charge for clinical trial 1.12.3 Request to charge for expanded access 1.12.4 Request for comments and advice 1.12.5 Request for a waiver 1.12.6 Exception from informed consent for emergency research 1.12.7 Public disclosure statement for exception from informed consent for emergency research 1.12.8 Correspondence regarding exception from informed consent for emergency research 1.12.9 Notification of discontinuation of clinical trial 1.12.10 Generic drug enforcement act statement 1.12.11 ANDA basis for submission statement 1.12.12 Comparison of generic drug and reference listed drug 1.12.13 Request for waiver for in vivo studies 1.12.14 Environmental analysis 1.12.15 Request for waiver of in vivo bioavailability studies 1.12.16 Field alert reports 1.12.17 Orphan drug designation 1.13 Annual report 1.13.1 Summary for nonclinical studies 1.13.2 Summary of clinical pharmacology information 1.13.3 Summary of safety information 1.13.4 Summary of labeling 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 1.13.11 Distribution data 1.13.12 Status of postmarketing study commitments and requirements 1.13.13 Status of other postmarketing studies and requirements 1.13.14 Log of outstanding regulatory business 1.13.15 Development safety update report (DSUR) 1.14 Labeling 1.14.1 Draft labeling 1.14.1.1 Draft carton and container labels 1.14.1.2 Annotated draft labeling text 1.14.1.3 Draft labeling text 1.14.1.4 Label comprehension studies 1.14.1.5 Labeling history 1.14.2 Final labeling 1.14.2.1 Final carton or container labels 1.14.2.2 Final package insert (package inserts, patient information, medication guides) 1.14.2.3 Final labeling text 1.14.3 Listed drug labeling 1.14.3.1 Annotated comparison with listed drug 1.14.3.2 Approved labeling text for listed drug 1.14.3.3 Labeling text for reference listed drug 1.14.4 Investigational drug labeling 1.14.4.1 Investigational brochure 1.14.4.2 Investigational drug labeling 1.14.5 Foreign labeling 1.14.6 Product labeling for 2253 submissions 1.15 Promotional material [promotional-material-audience-type] 1.15.1 Correspondence relating to promotional materials 1.15.1.1 Request for advisory comments on launch materials 1.15.1.2 Request for advisory comments on non-launch materials 1.15.1.3 Presubmission of launch promotional materials for accelerated approval products 1.15.1.4 Presubmission of non-launch promotional materials for accelerated approval products 1.15.1.5 Pre-dissemination review of television ads 1.15.1.6 Response to untitled letter or warning letter 1.15.1.7 Response to information request 1.15.1.8 Correspondence accompanying materials previously missing or rejected 1.15.1.9 Withdrawal request
Module 3 Quality
3.2 Body of data 3.2.S Drug substance [name, manufacturer] 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 Manufacturing Process and Process Controls 3.2.S.2.3 Control of Materials 3.2.S.2.4 Controls of Critical Steps and Intermediates 3.2.S.2.5 Process Validation and/or Evaluation 3.2.S.2.6 Manufacturing Process Development 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 Specification 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 Stability Commitment 3.2.S.7.3 Stability Data 3.2.P Drug product [name, dosage form, manufacturer] 3.2.P.1 Description and composition of the drug product 3.2.P.2 Pharmaceutical development 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 [name] 3.2.P.4.1 Specification(s) 3.2.P.4.2 Analytical Procedures 3.2.P.4.3 Validation of Analytical Procedures 3.2.P.4.4 Justification of Specifications 3.2.P.4.5 Excipients of Human or Animal Origin 3.2.P.4.6 Novel Excipients 3.2.P.5 Control of drug product 3.2.P.5.1 Specification(s) 3.2.P.5.2 Analytical Procedures 3.2.P.5.3 Validation of Analytical Procedures
3.2.P.5.4 Batch Analyses 3.2.P.5.5 Characterization of Impurities 3.2.P.5.6 Justification of Specification(s) 3.2.P.6 Reference standards or materials 3.2.P.7 Container closure system 3.2.P.8 Stability 3.2.P.8.1 Stability Summary and Conclusion 3.2.P.8.2 Postapproval Stability Protocol and Stability Commitment 3.2.P.8.3 Stability Data 3.2.A Appendices 3.2.A.1 Facilities and Equipment [name, manufacturer] 3.2.A.2 Adventitious agents safety evaluation [name, dosage form, manufacturer] 3.2.A.3 Novel excipients 3.2.R Regional information 3.3 Literature references
Module 4 Nonclinical Study Reports
4.2 Study reports 4.2.1 Pharmacology 4.2.1.1 Primary pharmacodynamics Study report [identification number] and related information Legacy clinical study report Pre clinical study report Synopsis Study report body Protocol or amendment Signatures investigators Audit certificates report Statistical methods interim analysis plan Inter-laboratory standardisation methods quality assurance Publications based on study Publications referenced in report Compliance and drug concentration data Data ta bula tion Data tabulation dataset legacy Data tabulation dataset send Data tabulation data definition Da ta list in g da ta set Data listing dataset Data listing data definition Analysis datasets Analysis dataset adam Analysis dataset legacy Analysis program Analysis data definition Safety report Assay validation Biomarkers Data monitoring review committees
See Primary pharmacodynamics Study report and related information for headings 4.2.3 Toxicology 4.2.3.1 Single dose toxicity [Species and route] Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.2 Repeat dose toxicity [Species, route, duration] Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.3 Genotoxicity 4.2.3.3.1 In vitro Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.3.2 In vivo Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.4 Carcinogenicity 4.2.3.4.1 Long term studies [Species] Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.4.2 Short or medium term studies Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.4.3 Other studies Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.5 Reproductive and developmental toxicity 4.2.3.5.1 Fertility and early embryonic development Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.5.2 Embryofetal development Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.5.3 Prenatal and postnatal development, including maternal function Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.5.4 Studies in which the offspring (juvenile animals) are dosed and/or further evaluated Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings
4.2.3.6 Local tolerance Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7 Other toxicity studies 4.2.3.7.1 Antigenicity Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7.2 Immunotoxicity Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7.3 Mechanistic studies Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7.4 Dependence Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7.5 Metabolites Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7.6 Impurities Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.2.3.7.7 Other Study report [identification number] and related information See Primary pharmacodynamics Study report and related information for headings 4.3 Literature references
Module 5 Clinical Study Reports
5.2 Tabular listing of all clinical studies 5.3 Clinical study reports and related information 5.3.1 Reports of biopharmaceutic studies 5.3.1.1 Bioavailability (BA) Study reports and related information Study report [identification] and related information Legacy clinical study report Synopsis (ICH E3, section 2) Study report body (E3 1, 3 to 15) Protocol or amendment (E3 16.1.1) Sample case report form (E3 16.1.2) IEC-IRB consent form list (E3 16.1.3) List description investigator site (E3 16.1.4) Signatures investigators (E3 16.1.5)
Specialty report Foreign clinical studies not under ind
5.3.1.2 Comparative BA and bioequivalence (BE) Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.1.3 In Vitro - in Vivo correlation Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.1.4 Reports of bioanalytical and analytical methods for human studies Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.2 Reports of studies pertinent to pharmacokinetics using human biomaterials 5.3.2.1 Plasma protein binding Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.2.2 Reports of hepatic metabolism and drug interaction studies Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.2.3 Reports of studies using other human biomaterials Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.3 Reports of human pharmacokinetic (PK) studies 5.3.3.1 Healthy subject PK and initial tolerability Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.3.2 Patient PK and initial tolerability Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.3.3 Intrinsic factor PK Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.3.4 Extrinsic factor Study reports and related information Study report [identification] and related information
See example under bioavailability (BA) Study reports and related information for headings 5.3.3.5 Population PK Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.4 Reports of human pharmacodynamic (PD) studies 5.3.4.1 Healthy subject PD and PK/PD Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.4.2 Patient PD and PK/PD Study reports and related information Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings 5.3.5 Reports of efficacy and safety studies [Indication] 5.3.5.1 Study reports and related information of controlled clinical studies pertinent to the claimed indication [type of control] Study report [identification] and related information See example under bioavailability (BA) Study reports and related information for headings
IND Mapping Section
Appendix 1 – Mapping Section...................................................................................................
IND
CFR Citation/Source CTD /STF Heading/*Attribute(s)
NUMBER TITLE MODULE NUMBER TITLE
312.23(a)(1) Cover sheet (Form FDA–1571) 1 1.1 **Forms form-type= FDAAA Certification of compliance: Form FDA 3674
1 1.1 **Forms form-type=
BsUFA Form FDA 3792: Biosimilar User Fee Cover Sheet
1 1.1 **Forms form-type=
312.31(b)(1) Statement of the nature and purpose of the information amendment
1 1.2 Cover letters
Change of address or corporate name NOTE: Includes DMF original address or corporate name or change in DMF address or corporate name
1 1.3.1.1 Change of address or corporate name
Change in contact/agent NOTE: Includes DMF original contact/agent or change in DMF contact/agent
1 1.3.1.2 Change in contact/agent
Change in ownership 1 1.3.1.3 Change in sponsor 312.52 Transfer of obligations to a contract research organization
1 1.3.1.4 Transfer of obligation
312.22(d) General principles of the IND submission
1.4.1 Letter of authorization
312.23(b) Written statement of authorization for references (copy of LOA received from DMF holders - submitted by BLA, NDA, or IND applicants)
1 1.4.2 Statement of right of reference
IND Mapping Section
CFR Citation/Source CTD /STF Heading/*Attribute(s)
NUMBER TITLE MODULE NUMBER TITLE
312.23(b) 312.23(a)(3)(ii)
Information previously submitted
1 1.4.4 Cross-reference to previously submitted information 312.38 Withdrawal of an IND 1 1.5.1 Withdrawal of an IND 312.45(a) Request for Inactive status 1 1.5.2 Inactivation request 312.45(d) Request to resume clinical investigation under an inactive IND
1 1.5.3 Reactivation request
Reinstatement request 1 1.5.4 Reinstatement request
PDUFA Agreements
Meeting request 1 1.6.1 Meeting request
PDUFA Agreements
Meeting background material 1 1.6.2 Meeting background materials
PDUFA Agreements
Correspondence regarding a meeting
1 1.6.3 Correspondence regarding meetings
FDAMA Fast track designation request 1 1.7.1 Fast track designation request FDAMA Fast track designation withdrawal request
1 1.7.2 Fast track designation withdrawal request
FDAMA Rolling review request 1 1.7.3 Rolling review request FDAMA Correspondence regarding fast track/rolling review
1 1.7.4 Correspondence regarding fast track/rolling review FDAMA Special protocol assessment request: clinical study
1 1.8.1 Clinical study
PDUFA Agreements Special protocol assessment request: carcinogenicity study
1 1.8.2 Carcinogenicity study
PDUFA Agreements Special protocol assessment request: stability study
1 1.8.3 Stability study
Animal efficacy study for approval under the animal rule
1 1.8.4. Animal efficacy study for approval under the animal rule PREA 312.47(b)(1)(iv)
Request for waiver of pediatric studies
1 1.9.1 Request for waiver of pediatric studies
IND Mapping Section
CFR Citation/Source CTD /STF Heading/*Attribute(s)
NUMBER TITLE MODULE NUMBER TITLE
312.54 Exception from informed consent for research
1 1.12.6 Exception from informed consent for emergency research 312.54 Public disclosure – exception from informed consent for research
1 1.12.7 Public disclosure statement for exception from informed consent for emergency research 312.54 IRB disapproval of exception from informed consent for research
1 1.12.8 Correspondence regarding exception from informed consent for emergency research
312.31(a)(2) Report regarding the discontinuation of a clinical investigation
1 1.12.9 Notification of discontinuation of clinical trial
312.23(a)(7)(iv)(e) Environmental analysis requirements
1 1.12.14 Environmental analysis
316 Subpart C Orphan Drug 1 1.12.17 Orphan drug designation 312.33(b)(6) Annual Report: A list of preclinical studies…
1 1.13.1 Summary of nonclinical studies
312.33(b)(5) Annual Report: A brief description of the drug’s actions…
1 1.13.2 Summary of clinical pharmacology information
312.33(b)(1) Annual Report: A narrative or tabular summary showing the most frequent and most serious adverse experiences by the body system
1 1.13.3 Summary of safety information
312.33(b)(2) Annual Report: A summary of all IND safety reports…
1 1.13.3 Summary of safety information
312.33(b)(3) Annual Report: A list of subjects who died…
1 1.13.3 Summary of safety information
312.33(b)(4) Annual Report: A list of subjects who dropped out…
1 1.13.3 Summary of safety information
IND Mapping Section
CFR Citation/Source CTD /STF Heading/*Attribute(s)
NUMBER TITLE MODULE NUMBER TITLE
312.33(b)(7) Annual Report: A summary of any significant manufacturing changes…
1 1.13.5 Summary of manufacturing changes
312.33(b)(7) Annual Report: A summary of any significant microbiological changes…
1 1.13.6 Summary of microbiological changes
312.33(a) Annual report individual study information
1 1.13.8 Individual study information
312.33(c) Annual Report: A description of the general investigational plan…
1 1.13.9 General investigational plan
312.33(f) Annual Report: A brief summary of significant foreign marketing developments…
1 1.13.10 Foreign marketing
312.33(g) Annual Report: Log of outstanding business…(optional)
1 1.13.14 Log of outstanding regulatory business
Development safety update report (DSUR)
1 1.13.15 Development safety update report (DSUR)
312.6 Draft labeling text 1 1.14.1.3 Draft labeling text Label comprehension studies 1 1.14.1.4 Label comprehension studies 312.23(a)(5) Investigator brochure 1 1.14.4.1 Investigator brochure 312.33(d) Annual Report: Investigators brochure…
1 1.14.4.1 Investigator brochure
312.23(a)(7)(iv)(d) Labeling 1 1.14.4.2 Investigational drug labeling Foreign labeling 1 1.14.5 Foreign labeling Proprietary names 1 1.18 Proprietary names Project BioShield Act of 2004
Emergency Use Authorization 1 1.19 Pre-EUA and EUA
312.23(a)(3)(iv) A brief description of the overall plan…
1 1.20 General investigational plan for initial IND
