IND Submissions: A Primer : Market Research Report

IND Submissions: A Primer

Published by: Barnett Educational Services

Published: Mar. 3, 2009

Chapter 1: Style Guides; Guidance Documents; What is a Style Guide?; Why do you Need a Style Guide?; Is a Style Guide Required?; Requirements from the Guidance Documents; Recommendations from the AMA & other sources; Headings; What will your headings look like?; Headers and Footers; What do you include in the header and/or footer?; List of Figures and Tables; Table and Figure Headings; Table and Figure Footers; Figure Style; Table Style; Header and Footer Numbering; Acronyms, Abbreviations and Definitions; Indentation; Lists; Text; Citation Reference; Title Page; Confidentiality Statement; Punctuation and Grammar; Numbering; Date Format; Superscript and Subscript; Breaks; Trademark; Bookmarks; Hyperlinks; GLP or GCP Statement; Proofreader’s Marks; What to do with Documents Received from Contributors?; How do you Create a Style Guide?; Tip; Training Users; Including Style Guide Elements as a Style Sheet; Color Copies; Tips; Electronic Examples; Reproduction prohibited 00:iii
Chapter 2: Creating and Use of Content Templates; Steps for Content Template Use; Why Use a Content Template?; Tips; Electronic Examples
Chapter 3: Submission Planning; Outlining the Submission; Submission Contributions; Submission Checklist & Creating the Timeline; Defining Timelines Using the; Submission Timing; Submission “Kick-off” Meeting; Submission “Kick-off” Memo; Submission Management; What to do with Corrections, Edits and Contributions from Previous Drafts; Monthly Planning Meetings and Tracking; Submission Scheduling; Bundling Items for Submission Every 30 Days; Submission Content Re-use; Tips; Electronic Examples
Chapter 4: Writing, Organization and Editing Tips; Writing Goals; Submission Pitfalls; Inverted Pyramid Writing Style; Areas of Contributions; Who Writes Submissions?; Contributions from Other Departments; Sections Written by Regulatory Personnel; Editing Process: What to do with all the Editorial Changes?; Individual Edits; Group Editing Sessions; Corrections, Edits and Contributions from Previous Drafts; Submission Content Re-use; Developing Key Messages
Chapter 5: Forms; Regulations; FDA Form 1571; Filling Out FDA Form; Cross-Referencing Multiple INDs; FDA Form 1571—Serial Number Errors; How Many Boxes can you Check in Item; FDA Form; FDA Form 3500A; Re-use Tips; Pagination; Reproduction prohibited 00:v; Print Single- or Double-Sided?; Form Expiration Dates; Original, Original, Who has the Original?; Tips; Electronic Examples; References
Chapter 6: Submission Basics; Regulations; What is a Submission?; Locking Down Sections; The Cover Letter; Information Previously Submitted; IND Submission Numbering; Tracking Submission Numbers; How does a Sponsor Address Duplicate Submission Numbers?; Number of Copies Needed; Desk Copies; Need for Agency Response; Where to Send the Submission; What Happens to a Submission When it Reaches FDA?; Shipping the Submission; Tracking Submission Shipment; Tips
Chapter 7: Assuring Quality in a Submission; Regulations; Supporting Documentation; QA of Submission Against Source or Supporting Documentation; Documenting the QA; How is Electronic Submission QA Different?; Electronic Checksum; Submission QA; Formatting; Pages; Page Orientation; Copy Quality; Length; Pagination; Tabs & Slip Sheets; Volume Size; Cover Letter; FDA Form; Binder Label; Bookmarks/Hyperlinks; Checksum; Tips; Electronic Examples
Chapter 8: Paper Publishing; Regulations & Guidance Documents; Publishing Tools/Technologies; Publishing Process: Hybrid; Binder Covers; Where to Find Binder Covers; Binder Specifications; IND Binder Cover Colors; FDA Perspective on Binders Usage and Color; Labels; Pagination; How to Handle Blank Pages; Copies for Submission; Tabs; Slip Sheets; Volumization; Scanners; Copiers; FDA Form; Assembling the Submissions; Shipping; Packing Carton Specifications; Tips; Electronic Examples; References
Chapter 9: Electronic Publishing; Regulations; Guidance Documents; MAPPs; Specifications; Electronic Publishing; What are Electronic Publishing Advantages?; Electronic Publishing Disadvantages; How do Electronic Submissions Relate to 21 CFR Part 11?; What is a Submission?; Publishing Process; Publishing Tools/Technologies; Tools Needed for Electronic Submissions; Challenges to Implementing an Electronic Publishing System; Scanners; Electronic CTD (eCTD); eCTD Basics Overview; XML; Metadata; XML Backbone; Style Guide; Directory Structure; Folder and File Naming Conventions; Reproduction prohibited 00:vii; Document Formats for eCTS; What File Formats Should I Use for Electronic Datasets?; Granularity; How Granularity Affects Content Templates; (TOC); Hyperlinks and Bookmarks; Pagination; PDF Overview; Security; Checksum; Lifecycle Management; Archive; Electronic Submissions Procedures; Media Requirements for Submission; Media Label Requirements; FDA Form; FDA Form; Quality Assurance; How do you Start the Electronic Publishing Process with the Agency?; Additional Elements to Include in the Cover Letter; If Submitting Electronically, are Paper Copies also Needed?; Document Information for Previous Submissions; Do you Resubmit Information Already Submitted in Paper?; Referencing Previously Submitted Information; Receipt Date For Electronic Submissions; eCTD Submission Waivers; Technical Problems or Questions; Electronic Submission Gateway; Involvement of IT; Commitments; Tips; Electronic Examples; References; Table 1: Glossary of Electronic Terms; Table 2: FDA ESG Monthly Submission Statistics
Chapter 10: Tracking Submissions, Agency Communication and Commitments; Regulations & Guidance Documents; Index History - Background; How to Organize an Index History; Outstanding Items and Questions Log; Index History Software Available; Agency Contact and Documentation; Sharing Files with Other Departments; Conclusion; Tips; Electronic Examples; Table 1: Index History Example—Word Processing Table; Table 2: Information to Track in a Premarketing Application Index History; Table 3: How to Create an OI or OQ List
Chapter 11: Filing Considerations; Regulations; Paper Archives; How to File; Where to File; What to File; Submission Copies; Electronic Archives; Electronic Submissions in Process; Electronic Record of Paper Submissions; How Long to Keep Records; How to Deal with Expanding Paper Files and Insufficient Space; Paper Filing System Options; File Folder and Binder Selection; File Folder Color Coding; Tips; Table 1: File Storage Options
Chapter 12: Managing References; Regulations; Guidance; What Needs to be Cited; Foreign References; FDA Recommended Style; How are Citations Located?; Citation Search Engines; What is PubMed; Process for Triaging Incoming References; Bibliographic Software; Pagination; Tabs & Slip Sheets; eCTD Format; Electronic Examples; Tips
Chapter 13: The Common Technical Document Format; Guidance Documents; Electronic CTD (eCTD); Hybrid CTD; CTD Guidance Documents Defined; What is a Module?; Sections of the CTD; What is an Overview?; What is a Summary?; Module 1 - Contents; Module 2 - Contents; 2.1 -; 2.2 - CTD Introduction; 2.3 - Overall Quality Summary; 2.4 - Nonclinical Overview; 2.5 - Clinical Overview; Reproduction prohibited 00:ix; 2.6 - Nonclinical Written and Tabulated Summary; 2.7 - Clinical Summary; Module 3 - Quality; 3.1 -; 3.2 - Body of Data; 3.3 - Literature References; Module 4 - Nonclinical Study Reports; 4.1 -; 4.2 - Study Reports and Related Information; 4.3 - Literature References; Module 5 - Clinical Study Reports; 5.1 -; 5.2 - Tabular Listing of all Clinical Studies; 5.3 - Clinical Study Reports; 5.4 - Literature References; Can you Add New Numbers into the CTD Format if Needed?; Does the CTD Replace the NDA and BLA?; Does the FDA Accept NDA’s and BLA’s in a non-CTD Format?; Where to Put the ISS and ISE?; How do you Deal With Multiple Quality Sections for Combination Products or Multiple Indications?; Transferring IND Information into the CTD Format; Once you Use the CTD Format, do you Always Need to Use it?; When can you Switch to the CTD Format?; Other Types of Submissions Using the CTD Format; How is Pagination Different in the CTD Format?; Electronic Examples
Chapter 14: Electronic Document Management Systems; Regulations; Guidance Documents; What is an EDMS?; Attributes of an Efficient Filing System; Why would a Company Use an EDMS System?; How does an EDMS Organize Documents?; How do you Implement an EDMS?; Converting from Paper to Electronic; FDA Definitions; EDMS and Electronic Publishing; Who “Owns” the EDMS?; Tips; Table 1. EDMS Components; Table 2. EDMS Critical Questions
Chapter 15: FDA Meeting Types; Regulations; Guidance Documents; Informal Meetings; Tips; Table 1. Meeting Types; Table 2. Meetings—By Phase of Investigation; Table 3. Clinical Investigations Phases
Chapter 16: Meeting Request; Regulations; Guidance Documents; Question and Issue Development; When to Request a Meeting; How to Request a Meeting; Submission; What to Expect from the Agency after the Request is Submitted; Meeting Request Components; Product Name and Application Number; Chemical name and structure; Proposed indication(s); Type of meeting being requested; Brief statement of the meeting’s purpose; List of the meeting’s specific expected objectives/outcomes; Preliminary proposed agenda; Draft list of specific questions, grouped by discipline; List of agency staff participants sponsor requests for the proposed meeting; Approximate date on which information package will be sent to the agency; Suggested meeting dates and times (i.e., morning or afternoon); Requesting an in-person meeting or teleconference; Cover Letter: Meeting Request; Length; Pagination; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples; Table 1. Types of Issues and Questions; Table 2. Meeting Request Components; Table 3. Draft Meeting Agenda
Chapter 17: Meeting Information Package; Regulations; Guidance Documents; Information Packages; Format for Meeting Packages; Submission; Agenda; Questions/Issues to be Addressed; Meeting Package Due Date; How Many Review Copies to Send; Length; Pagination; Cover Letter; FDA Form; Reproduction prohibited 00:xi; FDA Form; Quality Assurance; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; Tips; FDA Perspective; Electronic Examples; References; Exercise; Table 1. Information Package—Submission Contents; Table 2. Information Package—Sample for an End-of-Phase 2 Meeting; Table 3. Meeting Types
Chapter 18: Meeting Follow-Up and Planning; Regulations; Guidance Documents; Setting the Date; Meeting Package Due Date; Meeting Rehearsal; Conducting the Meeting; External Experts; In Person or Over the Phone?; Pre-Meeting Minutes Availability; Canceling the Meeting; Length of Meeting; FDA Perspective; Tips; Electronic Examples
Chapter 19: Meeting Minutes; Regulations; Guidance Documents; Agency Perspective; Timing of Agency Meeting Minutes; Sponsor Perspective; Reaching Team Consensus on Meeting Minutes; Timing of Sponsor Meeting Minute Submission; Before the Meeting: Requesting the Agency’s Pre-Meeting Minutes; Whose Meeting Minutes are Official?; Disagreement between Sponsor and Agency Meeting Minutes; Length; Pagination; Format; Cover Letter: Sponsor Meeting Minutes; Cover Letter: Letter for Clarification; FDA Form; FDA Form; Assembling the Submissions; Tabs & Slip Sheets; Paper Publishing; eCTD Format; Commitments; FDA Perspective; Waiting Period; Tips; Electronic Examples; References
Chapter 20: Responding to an Agency Request for Additional Information; Regulations; Getting Team Input; Timeline for Response; Format; Length; Pagination; FDA Form; FDA Form; Other Items to Send with Response; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples
Chapter 21: Dispute Resolution; Regulations; Guidance Documents; Initial Steps to Resolve a Dispute, Chain of Command; Other Kinds of Disputes; Using Consultants; Special Advisory Committee; When to Use Dispute Resolution; Ombudsman; Dispute Resolution Cover Letter; Where to Send Formal Dispute Resolution Requests; Dispute Resolution Submission; What Happens to Requests for Dispute Resolution?; Agency Response; Agency Timeline for Response—PDUFA Products; Agency Timeline for Response—Non-PDUFA Products; Meeting Minutes; Publishing Information; Real World Example; Tips; Electronic Examples; References; Figure 1: Chain of Command for Dispute Resolution
Chapter 22: Types of INDs; Regulations; Commercial IND; Investigator or Research IND; Emergency Use IND; Treatment IND; Screening or Exploratory IND; Table 1. CDER Original INDs Received:Calendar Years 1986-
Chapter 23: Emergency, Compassionate or Single Use INDs; Regulations; When do you Use the Compassionate/Emergency/Single Use IND?; Emergency Use IND; Single Use IND; Compassionate Use IND; How do you Apply for the Compassionate/Emergency/Single Use IND?; Physician Request for an IND for Emergency, Compassionate or Single Use, Submission Contents; What should the Sponsor Submit to Complete the IND File for the Physician?; What does the Sponsor Need to do for the Physician IND?; What does the Physician Need to Provide to the Sponsor?; Publishing; Commitments; Waiting Period; Tips; Other Perspectives; References
Chapter 24: Treatment Use IND; Regulations; Guidance Documents; When to Apply for a Treatment IND?; Treatment IND Submitted by A Sponsor; A Treatment Protocol is to be Supported by the Following; Treatment IND Submitted by a Physician Investigator; ClinicalTrials.gov; Charging for Investigational Drug; When do Sponsors Usually Request to Charge?; FDA Form 1571 - Special Box for Both Treatment IND and Charging for an Investigational Drug?; Tips; Electronic Examples; References
Chapter 25: Exploratory or Screening INDs; Regulations; Guidance Documents; MAPPs; What is an Exploratory IND?; Why Submit an Exploratory IND Instead of a Traditional Commercial IND?; How is an Exploratory IND Different from a Traditional IND?; How do you Apply for the Exploratory IND?; Clinical Section; What Clinical Information should be Included in an Exploratory IND?; Types of Studies; Chemistry, Manufacturing and Control Section; Pharmacology & Toxicology Section; Follow-up INDs; IND Withdrawal; What are FDA Reviewers Looking For?
Chapter 26: The IND Team and How to Start the IND; IND Rules; IND Application; Who Makes Up the Team; IND Strategy Development Team; The IND Strategy; How to Start the IND; Managing the Timeline; Electronic Examples
Chapter 27: IND Basics and Items 1 and 2; Regulations; Guidance Documents; MAPPs; Why Submit an IND?; The IND application must contain information in three broad areas; How are Drug and Biologic INDs Different?; Drugs; Biologics; Confidentiality of IND Submission; Building the IND; Cover Letter; Item 1.0—FDA Form; Item 2.0— (TOC); IND in a CTD Format; Why Submit in the CTD Format?; If you submit in the CTD format, will you have to continue to submit in the CTD format?; Numbering of the IND Amendments; IND Number; How Drug and Biologic IND Numbers are Different; How Drug and Biologic IND Numbers have Changed; Where to Send the Initial IND?; Length; Pagination; Quality Assurance; Does Each Section have its Own Volume?; Should Sections Break Across Volumes?; FDA Receipt of the IND; IND Effective Date; Why is this Date Important?; Reproduction prohibited 00:xv; What do FDA Reviewers Want?; Medical Review; Chemistry Review; Pharmacology/Toxicology Review; Safety Review; Is an IND Approved?; IND Submission Outcome; What typical deficiencies are found?; eCTD Format; Assembling the Submissions; Tabs & Slip Sheets; Paper Publishing; Commitments; Waiting Period; Tips; Other Perspectives; Electronic Examples; IND Exercise; Table 1. IND in a CTD Format; Figure 1: FDA Internal IND Review Process
Chapter 28: Clinical IND Items 3, 4, 5 and 6; Regulations; Guidance Documents; What is a Clinical Investigation?; What is an Investigator?; What is a Human Subject?; What is an Adequate and Well-Controlled Clinical Trial?; Waiver of Requirements for an Adequate and Well-Controlled Clinical Trial; General Requirements for Use of an Investigational New Drug in a Clinical Investigation; When does an IND go into Effect?; When can Drug be Shipped?; Is an IND Required with a Phase I Protocol?; Submitting Multiple INDs for the Same Compound; Item 3.0—Introductory Statement and General Investigational Plan; Section 3.0 Tips—Introductory Statement; Section 3.0—General Investigational Plan; Section 3.0 Tips—General Investigational Plan; Item 4.0—Reserved; Item 5.0—Investigator’s Brochure; Section 5.0—Tips; Section 5.0—Publishing; Item 6.0—Phase 1 Clinical Protocol(s); Additional Items to Send with the Protocol: Informed Consent Form (ICF); What are the Elements of Informed Consent?; Required; Recommended; Additional Items to Send with the Protocol: Case Report Forms; Section 6.0—Tips; Section 6.0—Publishing; How are Biologics Different?; What is the Difference Between Phase I and Phase II Clinical Trial Protocols?; Length; Pagination; Electronic Examples; Table 1. Types of Clinical Trial Designs
Chapter 29: Item 7: Chemistry, Manufacturing and Controls; Regulations; Guidance Documents; MAPPs; Phase; How Do GMPs Fit?; 7.0—Introduction; 7.A—Drug Substance; Drug Substance: Tips; 7.B—Drug Product; Drug Product: Tips; 7.C—Placebo; Placebo: Tips; 7.D—Clinical Labeling; Clinical Labeling: Tip; 7.E—Environmental Assessment; 7.F—Combination Products: The Device “CMC” Section; 7.G—References; When to Start Writing this Section; What are the Minimum Requirements for an IND?; Managing the Timeline; How Biologics Submission would Differ; Tracking of Lots from all Studies; Agency Concerns, Reasons for a Clinical Hold based on the CMC Section; Length; Pagination; Tips; Table 1. Glossary of CMC Terms
Chapter 30: Item 8: Nonclinical IND; Regulations; Guidance Documents; MAPPs; Introduction; Why are Animal Studies Required by Regulatory Agencies?; Typical Nonclinical Safety Studies; Study Strategy; What Types of Studies are Needed to Support the Filing of the IND?; Choice of Animal Model; What is an Integrated Summary?; What is an Integrated Summary? (continued); Section 8—Pharmacology; Section 8—Toxicology; Section 8.D—Qualifications of the Individual(s) who Evaluated the Animal Safety Data; 8.E—Location of Records; Reproduction prohibited 00:xvii; 8.F—GLP Compliance Statement; 8.G—Bibliography/Supportive Literature; Order of Studies; Order of Animals; Route of Administration Order; Dosing Order; Managing the Timeline; Pediatric Population; How a Biologics Submission would Differ; Should Final Study Reports be Included with the Initial IND?; Length; Pagination; Study Report Format; Tips; Electronic Examples; References; Table 1. Nonclinical Study Overview and Considerations; Table 2. Overview of Typical Nonclinical Studies Needed for IND*; Table 3. Glossary of Nonclinical Terms
Chapter 31: IND: Items 9, 10, 11 and Potentially 12; Regulations; Guidance Documents; Item 9.0—Previous Human Experience with the Drug; What Will Section Look Like?; 9.0—Previous Human Experience with the Drug; 9.A—Drug Previously Investigated or Marketed in the U.S. or Foreign Country; 9.B—Drug Combination Previously Investigated or Marketed; 9.C—Drug Withdrawn from Marketing; If this section is not applicable, what do you write?; Item 10.0—Additional Information; What Will This Section Look Like?; 10.0—Additional Information; 10.A—Drug Dependence and Abuse Potential; 10.B—Radioactive Drugs; 10.C—Pediatric Studies; 10. D—Other Information; If this section is not applicable, what do you write?; Item 11.0 - Relevant Information; What Will This Section Look Like?; 11.0—Relevant Information; 11.A—Information Previously Submitted; 11.B—Material in a Foreign Language; If this section is not applicable, what do you write?; Item 12.0—References; What Will This Section Look Like?; 12.0—References; 12.1—Bibliography; 12.2—Copies of Pertinent Literature; Tabs & Slip Sheets; Electronic Examples
Chapter 32: Letters of Cross Reference or Authorization (LOA); Regulations; Guidance Documents; What is a Cross-Reference or Letter of Authorization (LOA)?; Why Request an LOA?; CMC Section of IND or NDA; Drawbacks to LOAs and Consequences to IND Holders for Deficiencies; When do you Use or Need a LOA?; Agent or Consultant LOAs; What Type of Information Needs to be Included in a LOA from a Vendor?; Referencing Another IND; Referencing a DMF; Emergency/Single/Compassionate Use IND Cross-Reference; Who gets Copies of the Letter?; Copy to Applicant, Sponsor or Other Holder; What to do with Original?; Managing the Timeline; Submitting DMF/IND Cross-Reference Cover Letter Format—from a Vendor; Submitting DMF/IND Cross Reference Cover Letter Format - on Behalf of Company, for a Vendor; Length; Pagination; FDA Form; Assembling the Submissions; Paper Publishing; Other Items to Send With the LOA; eCTD Format; Electronic Examples
Chapter 33: IND Amendments; Regulations; Guidance Documents
Chapter 34: New Protocols, Protocol Amendments, Protocol Concept Sheets and Synopses; Regulations; Guidance Documents; Typical Types of Protocol Amendments; Protocol by Phase of Investigation; Managing the Timeline; When to Send In?; When Can a Clinical Trial Begin?; Include the Model Informed Consent Form?; Amendment Process; What Triggers an Amendment; Length; Pagination; Format; Cover Letter: Initial Protocol; Cover Letter: Protocol Amendment; Cover Letter: Protocol Synopsis; FDA Form; FDA Form; Reproduction prohibited 00:xix; Quality Assurance; Items to Submit with the Protocol; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; Waiting Period; Tips; Other Perspectives; Electronic Examples
Chapter 35: Transfer of Obligations; Regulations; Sponsor Responsibilities; What Responsibilities are Usually Transferred to a CRO?; When to Submit?; Submission Length; Pagination; Format; Cover Letter; FDA Form; FDA Form; eCTD Format; Assembling the Submissions; When to Update; Tips; Other Perspectives; Electronic Examples; Table 1. Transfer of Obligations (Example)
Chapter 36: Investigator’s Brochure Update; Regulations; Guidance Documents; When to Update; What Triggers an Update; Who gets the Update?; Managing the Timeline; Length; Pagination; Format; Cover Letter; FDA Form; FDA Form; Quality Assurance; Items to Send with the IB; Assembling the Submission; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Electronic Examples; Tips
Chapter 37: IND Safety Reports; Regulations; Guidance Documents; What is an Adverse Event; What is a Serious Adverse Event; ICH E2A Definition of an Adverse Drug Reaction (ADR) or Serious Adverse Event (SAE); ICH E2A Definition of an Unexpected Adverse Drug Reaction; 21 CFR �312.32 Definition of an Unexpected Adverse Drug Experience; 21 CFR �312.32 Defines Serious Adverse Events; How are SAEs Reported?; Notification Timeframe; Reporting Timeframes—7 Day Report; Reporting Timeframes—15 Day Report; Reporting Timeframes—Follow-Up Information; SAE Numbering; Reporting Sources; Report Format; Narrative Format—Minimum Requirements; Narrative Format—Preferred Contents; Completing FDA Form 3500A; Submitting an SAE; Questions About Safety Reports or Completing Forms; Managing the Timeline; Tracking SAEs; Multiple INDs; How Biologics are Different; Who Else Needs to be Notified?; Length; Pagination; Cover Letter: Initial IND Safety Report—FDA Form 3500A; Cover Letter: Initial IND Safety Report—Narrative; Cover Letter: IND Safety Report for Follow-Up, FDA Form 3500A; Cover Letter: IND Safety Report for Follow-Up, Narrative; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples; Table 1. Reporting Matrix; What is MedDRA?
Chapter 38: Investigator’s Submission; Regulations; Table of Investigators; Managing the Timeline; FDA Form 1572 Updates; Reproduction prohibited 00:xxi; How Biologics Submissions Differ; Curriculum Vitae’s (CV); Cover Letter; Other Items to Send with Submission; Length; Pagination; Assembling the Submission; FDA Form; FDA Form; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; Waiting Period; Tips; FDA Perspectives; Other Perspective; Electronic Examples; Table 1. Sample Table of Investigator
Chapter 39: Fast Track Designation; Regulations; Guidance Documents; Why would a Sponsor Apply for Fast Track?; Criteria that must be Met for Application; What is a Serious Condition?; What is Life-Threatening?; What is Severely Debilitating?; What is an Unmet Medical Need?; What to do when a Therapy Currently Exists?; Managing the Timeline; Timing During Development; Sections of Application; 1.0—Summary of the Request; 2.0—Indication or Disease Overview; 3.0—Disease is a Serious Life-Threatening Condition; 4.0—Disease is an Unmet Medical Need; 5.0—How Drug X Has Potential to Fill Unmet Medical Need; 6.0—Conclusion; 7.0—Bibliography/Supportive Literature; 8.0—Appendices; Outcomes; Designation Letter; Nondesignation Letter; Nondesignation Appeal and Resubmission; Revocation of Fast Track Designation; Continuous Marketing Application Pilot Programs Defined; Length; Pagination; Submission Header; Cover Letter; Cover Letter: Resubmission (if necessary); FDA Form; FDA Form; Assembling the Submission; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with Request; eCTD Format; Commitments; Waiting Period; Tips; FDA Perspectives; Electronic Examples; Fast Track Applications to Date; Number of Fast Track Applications Received; Fast Track Products Approved Since; References
Chapter 40: Clinical Study Reports; Regulations; Guidance Documents; Format; Managing the Timeline; Length; Pagination; Cover Letter; FDA Form; FDA Form; Quality Assurance; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with the CSR; CTD Format; Commitments; Tips; Other Perspectives; FDA Perspectives; Electronic Examples
Chapter 41: Pediatric & Geriatric Waiver/Deferral; Regulations; Pediatric Guidance Documents; Geriatric Guidance Documents; Pediatric Age Groups Defined; Geriatric Age Groups Defined; What is a Waiver?; What is a Deferral?; What is Meaningful Therapeutic Benefit?; Full Waiver; Partial Waiver; Reproduction prohibited 00:xxiii; Why will a Waiver be Granted?; Deferral; How will Waiver/Deferral Request and Response be Acknowledged by FDA?; Can a Waiver/Deferral Agreement be Revoked?; Sections of Pediatric Waiver and Partial Waiver Application; 1.0—Introduction; 2.0—Age Group(s) Included in Waiver Request; 3.0—Statutory Information; 4.0—Bibliography/Supportive Literature; How Does the Partial Waiver Differ from the Full Waiver?; Sections of a Pediatric Deferral Application; 1.0—Introduction; 2.0—Indication; 3.0—Age Group(s) Included in Waiver Request; 4.0—Reasons for Not Including All Pediatric Patients; 5.0 —Reasons for Deferring Pediatric Studies; 6.0—Pediatric Plans Submitted to the Agency; 7.0—Bibliography/Supportive Literature; 8.0—Appendices; Geriatric Patients in Safety Database; Geriatric Waiver; Sections of Geriatric Waiver and/or Deferral; FDA Response—Waiver; FDA Response—Deferral; Timing of Waiver Request; Alternative: Submit with the NDA; Consequences of Not Applying for a Waiver During the IND or NDA Phase; Consequences of Not Responding to a Request for Pediatric Trials or Additional Information; Length; Pagination; Submission Header; Cover Letter: Pediatric Full Waiver (if a Stand Alone Submission); Cover Letter: Pediatric Partial Waiver (if a Stand Alone Submission); Cover Letter: Pediatric Deferral (if a Stand Alone Submission); Cover Letter: Geriatric Waiver (if a Stand Alone Submission); FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with Waiver; eCTD Format; Commitments; Waiting Period; Other Perspectives; Electronic Examples
Chapter 42: Responding to Clinical Holds; Regulations; Guidance Documents; Complete Clinical Hold; Partial Clinical Hold; Discussion of Deficiency; How does a Clinical Hold Affect a Trial?; How is a Sponsor Notified of a Clinical Hold?; Reasons for a Clinical Hold; Phase; Phase 2 or; Sponsor Response to a Clinical Hold; Agency Timeline for Response; Agency Actual Response Time; If Clinical Hold Issues are not Resolved, what are the Next Steps?; When a Clinical Hold is Lifted; How is a Sponsor Notified when a Clinical Hold is Lifted?; If Clinical Hold is Never Lifted?; Managing the Timeline; Length; Pagination; Cover Letter/Format for Clinical Hold Response; Sending in an Amendment to the Clinical Hold Response; FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with a Clinical Hold Response; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples; References; Table 1. Overview of Responses to Clinical Holds; Table 2. 2006 Responses to Clinical Holds (CBER/CDER)
Chapter 43: Special Protocol Assessment - Clinical Protocols; Regulations; Guidance Documents; What is a Special Protocol Assessment (SPA)?; How does the SPA Process Work?; SPA Overview; Advisory Committee Review; SPA Request Outcome; Review; Denial; Managing the Timeline; Agency Timeline for Review and Response; Protocol Amendments During the Review Period; Protocol Amendments After the Review Period; Length; Pagination; Format; Background Summary; Cover Letter: Special Protocol Assessment Request; FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with Protocol; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples; References; Table 1. Special Protocol Assessments, Number Received Per Year; Table 2. Special Protocol Assessments (CBER/CDER)
Chapter 44: Statistical Analysis Plan; Regulations; Guidance Documents; Managing the Timeline; Length; Pagination; Format; Cover Letter: SAP; FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD; Commitments; Waiting Period; Tips; Electronic Examples
Chapter 45: Clinicaltrials.gov and FDA Form 3674; Regulations; Guidance Documents; What Trials and Information must be Posted in the Databank?; Foreign Trial Site Information; Managing the Timeline/When to Submit Information; What Information do you Post on Clinicaltrials.gov?; How do you Post on Clinicaltrials.gov?; How do you Manage Protocol Amendments?; How Often should the Information be Updated?; How Long will Information Remain on ClinicalTrials.gov?; Treatment INDs and Expanded Access Programs; Format; Is the Sponsor’s IND Number Disclosed on the Site?; FDA Form; What Submissions don’t have to have a FDA Form 3674?; Do you have to Comply?; Noncompliance Enforcement & Fines; Paper Publishing; eCTD Format; Commitments; Waiting Period; Tips; Other Perspectives; Electronic Examples; References
Chapter 46: Changes in the Chemistry, Manufacturing and Controls Section; Regulations; Guidance Documents; MAPPs; What can Change Between the Initial IND and Phase 3?; When to Submit?; What are Requirements?; Phase 2/3 Introduction; Phase 2—Drug Substance; 7.A—Drug Substance; Phase 2—Drug Product; 7.B—Drug Product; Phase 3—Drug Substance; 7.A—Drug Substance; Phase 3—Drug Product; 7.B—Drug Product; Tracking of Lots from all Studies; Length; Pagination; Format; Tips
Chapter 47: Comparability Protocols - Chemistry, Manufacturing and Controls Information; Regulations; Guidance Documents; What is a Comparability Protocol?; Why Use a Comparability Protocol?; What is the Agency Looking for?; What Must the Sponsor Prove?; Evaluation of a Manufacturing Change and Adverse Effects; When Nonclinical and Clinical Lots are Different; Conducting Additional Nonclinical or Clinical Trials to Verify Comparability; What Kind of Nonclinical or Clinical Trials Might be Needed to Establish Safety and Efficacy of the; Changed Product?; Nonclinical; Clinical; How Many Changes are Allowed?; Comparability Protocol Proposal Outcome; Why is a Comparability Protocol Important?; How a Biologics Submission would Differ; Reproduction prohibited 00:xxvii; Managing the Timeline; What if Study Results do not Meet the Criteria Specified in the Approved Comparability Protocol?; How is an Approved Comparability Protocol Modified?; What Information is Typically Included in the Comparability Protocol?; Format - Proposed Protocol; Format: Protocol with Study Results; Length; Pagination; Cover Letter: Initial Protocol; Cover Letter: Protocol Results; FDA Form; Other Items to Send with Protocol; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Waiting Period; Tips; Other Perspectives; Electronic Examples; Table 1. Glossary
Chapter 48: Special Protocol Assessment— Stability; Regulations; Guidance Documents; What is a Special Protocol Assessment (SPA)?; How Does the SPA Process Work?; SPA Overview; Managing the Timeline; Agency Timeline for Review and Response; SPA Request Outcome; Review; Denial; Protocol Amendments During the Review Period; Protocol Amendments After the Review Period; Length; Pagination; Format; Background Summary; Cover Letter: Special Protocol Assessment Request; FDA Form; Assembling the Submissions; Paper Publishing; Other Items to Send with Protocol; Tabs & Slip Sheets; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples; References
Chapter 49: Nonclinical Study Reports & Amendments; Regulations; Guidance Documents; When does the 120 Day Clock Start?; Managing the Timeline; Length; Pagination; Format; Cover Letter: Study Submission; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with the Study Report; eCTD Format; Commitments; Tips; Electronic Examples
Chapter 50: Nonclinical Study Waivers; Regulations; How is a Waiver Granted?; Managing the Timeline; Submission Format; How would a Biologics Submission Differ?; Length; Pagination; Cover Letter: Nonclinical Waiver (if a Stand Alone Submission); FDA Form; Assembling the Submission (if a Stand Alone Submission); Paper Publishing; Tabs & Slip Sheets; Other Items to Send with Waiver; eCTD Format; Waiting Period; Electronic Examples
Chapter 51: Special Protocol Assessment— Carcinogenicity; Regulations; Guidance Documents; What is a Special Protocol Assessment (SPA)?; How does the SPA Process Work?; How is the Carcinogenicity SPA Process Different?; SPA Overview; Carcinogenicity Assessment Committee (CAC); Managing the Timeline; Agency Timeline for Review and Response; SPA Request Outcome; Review; Reproduction prohibited 00:xxix; Denial; How Big is a SPA Request?; Pagination; Format; Background Summary; Cover Letter: Special Protocol Assessment Request - Notification; Cover Letter: Request for Special Protocol Assessment; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with SPA Request; eCTD Format; Commitments; Waiting Period; Tips; Electronic Examples; References
Chapter 52: IND Annual Report; Regulations; Guidance; Due Date; IND Effective Date; Reporting Period; Data Cut-off Date; Clean vs. Dirty Data; Coordinating the AR Team; Managing the Timeline; Sections of the Annual Report; 1.0 - Individual Study Information; 2.0 - Clinical Summary; 2.A - Adverse Events; 2.B - IND Safety Reports; 2.C - Deaths; 2.D - Drop Outs Due to Adverse Events; 2.E - Action of the Drug or Biologic; 3.0 - Nonclinical Study Update; 4.0 - Chemistry Manufacturing and Control Changes; 4.A - Summary; 4.B - Stability; 5.0 - General Investigational Plan; 6.0 - Investigator’s Brochure; 7.0 - Phase I Protocol Modifications; 8.0 - Foreign Marketing Developments; 9.0 - Outstanding Business; How are Biologics Annual Reports Different?; Section 2.F: Confirmation that Clinical Oversight and Monitoring are being Conducted in Accordance with; the March 6, 2000 Gene Therapy Response Letter; Section 4.C: Changes in Manufacturing Procedures; Section 4.D: QA and QC Audit Summary; Managing Multiple IND Annual Reports; Do you Combine Multiple Sections on the Same Page?; Length; Pagination; Cover Letter; FDA Form; FDA Form; Other Items to Send with Annual Report; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; eCTD Format; Commitments; FDA Perspective; Tips; Electronic Examples
Chapter 53: Orphan Drug Annual Report; Regulations; Guidance; Orphan Drug Annual Reporting Regulations; Due Date; Coordinating the IND and Orphan Annual Reports; How does the Orphan Drug Annual Report Differ from the IND Annual Report?; Managing the Timeline; Length; Pagination; Cover Letter: Annual Report Using IND Annual Report; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Electronic Publishing; Commitments; Tips; Electronic Examples
Chapter 54: The CMC Annual Report 54:433; Regulations54:433; Managing the Timeline54:434; Length54:434; Pagination54:434; Format54:434; Cover Letter54:434; FDA Form 157154:435; Assembling the Submissions54:435; Paper Publishing54:435; Tabs & Slip Sheets54:435; eCTD Format 54:435; Electronic Examples54:435
Chapter 55: Orphan Drug Designation; Regulations; Guidance Documents; Forms; Office of Orphan Products Development; Why Apply for Designation?; Qualifications for Orphan Drug Designation; When Request Designation; Sections of Applications; 1.0—Statement of Orphan-Drug Designation Request; 2.0—Information on Sponsor’s Contact Person or Resident Agent; 3.0—Description of Rare Disease or Condition; 4.0—Description of the Drug and Rationale for Use; 5.0—Clinical Superiority Explanation, if Applicable; 6.0—Medical Plausible Subset; 7.0—Summary of Drug’s Regulatory Status and Marketing History; 8.0—Prevalence of Drug’s Target Population or Cost Recovery, if Applicable; 9.0—Statement of Real Party of Interest; 10—Other, if Applicable; Copies of Literature Citations; Population Prevalence; Scientific Rationale; Cross Reference to IND Information; Pediatric Subset Request; Application Challenges; Managing the Timeline; Orphan Grants; How Much Grant Money is Available?; How are Awards made?; Who may Apply?; How are Applications Reviewed?; List of Orphan Designations and Approvals; How to Track and File Maintenance Information; Length; Pagination; Format; Cover Letter; FDA Form; FDA Form; Assembling the Submissions; Tabs & Slip Sheets; Paper Publishing; Electronic Submissions; Where to Send; Commitments; Waiting Period; Outcome; Maintenance/Amendments to the Application; Revocation of Orphan Designation; Other Perspectives; Tips; Electronic Examples; References
Chapter 56: Developing the Package Insert; Regulations; Guidance Documents; What is a Label?; What is Labeling?; What is a Package Insert?; Sections of the Package Insert; Item; Regulation; Annotation; Why does the PI Need to be Annotated?; Highlights Section; When is the Highlight’s Section Required?; Full Prescribing Information: Contents; Boxed Warning; Agency Format Requirements; How to Assemble the First Draft of the Package Insert; Managing the Timeline; Length; Pagination; Submission to Agency; Electronic Examples
Chapter 57: Target Product Profile; Regulations; Guidance Documents; Additional Reasons to Use the TPP; Why Submit a TPP?; Can the TPP be Submitted without a Meeting Package?; TPP Advantages; TPP Use with a Meeting Package; Target Product Profile Format; Target; Annotations; Comments; Sections it Covers; How to Use the Tool?; How to Assemble the Initial TPP?; Managing the Timeline; Length; Pagination; Cover Letter: TPP Submission without a Meeting Request; FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Reproduction prohibited 00:xxxiii; eCTD Format; Tips; Electronic Examples
Chapter 58: USAN and INN Name Development; Laws and Regulations; Why is a USAN Name Important?; How do you Create a USAN Name?; What Research on the Chosen Name should be Done Before Submission?; Where do you Find the Application?; What are the Costs Associated with a USAN?; What Information will you Need for the Application?; What Happens After the Application is Submitted?; What Information will be Received Back from USAN after the Initial Application is Filed?; Does USAN Accept all Proposed Names?; USAN Facilitation of an INN Expert Group Review; When is the Nonproprietary Name Official?; Does the USAN Confirmation Letter Need to be Sent to the Agency?; Timeline; USP; INN Overview; Length; Waiting Period; Tips; Electronic Examples; References; Table 1. Decoding the “Name” Usage
Chapter 59: Trade or Proprietary Name Development; Regulations; Guidance; How Many Names can a Drug have?; How does a Company Develop a Trade Name?; What Research should a Sponsor Conduct Before Submitting a Trade Name to the Agency for Review?; What does FDA Look for in the Review of a Trade Name?; The Trade Name Assessment Process; A Proposed Trade Name may be Rejected Under any of the following Scenarios; When Submit a Trade Name Evaluation?; Same Drug, Different Indication, Different Trade Name?; Why do Companies Develop a Trade Name and Use it During the Development Process?; When can a Sponsor Start Using the Trade Name on Documents?; Documenting the Use of a Trivial or Trade Name Throughout the Drug’s Development; Review Timeline; Alternative Trade Name Submission Method; Appeal; Pilot Program; Length; Pagination; Cover Letter; FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with Submission; eCTD Format; Tips; Other Perspectives; Electronic Examples; References; Table 1. Decoding the “Name” Usage
Chapter 60: Change in Company Name, Address, Contact Person, Medical Monitor or Ownership; Regulations; Managing the Timeline; Who Needs to be Notified?; What Needs to be Changed or Updated?; Company Bought; Change in Agency Contact Person; Change in Medical Monitor; Length; Pagination; Letter: Name Change; Letter: Change in Ownership (from Company Being Acquired); Letter: Change in Ownership (by Acquiring Company); Letter: Change in Address; Letter: Change in Contact Person; Letter: Change in Medical Monitor; FDA Form; FDA Form; Assembling the Submissions; Paper Publishing; Tabs & Slip Sheets; Other Items to Send with Submission; eCTD Format; Electronic Examples
Chapter 61: Inactivating, Withdrawing, Terminating, Discontinuing or Reinstating an IND; Regulations; Inactivating an IND; Withdrawal of an IND; Termination of an IND; How does Notification of Termination Happen?; Reinstatement Request; How do you Reinstate an IND?; Clinical Investigations Under an IND on Inactive Status may only Resume; Length; Pagination; Format; Cover Letter: Inactivate; Cover Letter: Withdrawal; Cover Letter: Reinstatement; Reproduction prohibited 00:xxxv; FDA Form; FDA Form; Assembling the Submissions; If it is a Reinstatement Submission; Tabs & Slip Sheets; Paper Publishing; eCTD Format; Waiting Period; Tips; Electronic Examples
Chapter 62: Drug and Biologics Master Files; Regulations; Guidance Documents; What is a Drug Master File?; Who would Apply for a DMF?; Types of Drug Master Files; What happened to Type I DMFs?; Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel; Type II: Drug Substance, Drug Substance Intermediate, and Material Used in their Preparation, or Drug Product; Drug Substance Intermediates, Drug Substances and Material Used in their Preparation; Drug Product; Type III: Packaging Material; Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in their Preparation; Type V: FDA Accepted Reference Information; Environmental Assessment; Stability; How to Submit Information not in a Specific DMF Type?; Agency Receipt of DMF; DMF Acknowledgement Letter; Agency Review of DMFs; How does a DMF Review Differ from an IND Review?; For IND Applications, typically; While for DMFs; Who Must File a DMF?; DMF Holder Obligations; Updating the DMF; Who to Notify of Updates?; DMF Amendments; Annual Update; Transfer of Ownership; Do you Refer to your IND or DMF?; Public Disclosure of DMF Information; Where to Send a DMF?; CDER; CBER; Major Reorganization of a Drug Master File; Length; Pagination; IND or CTD Format; Format; Why do you Need an LOA?; Who Else Needs a Copy of the LOA?; List of People Authorized to Reference DMF; DMF Closure; Inactivation of DMF; Reactivating a DMF; Cover Letter: DMF Submission; Cover Letter: DMF Amendments; Cover Letter: Letter of Authorization; FDA Form; Assembling the Submissions; Paper Publishing; Binder Specifications; eCTD Format; Tabs & Slip Sheets; Commitments; Waiting Period; Tips; Electronic Examples; References; Table 1. DMF Glossary; About Cambridge Healthtech Institute; Cambridge Healthtech Institute Conferences (www.healthtech.com); The Pharmaceutical Strategy Series (www.pharmaseries.com); Barnett International (www.barnettinternational.com); Insight Pharma Reports (www.insightpharmareports.com); CHI’s Marketing Services (http://proservices.healthtech.com); Cambridge Meeting Planners (http://proservices.healthtech.com); Cambridge Healthtech Associates (www.chacorporate.com); Cambridge Healthtech Media Group (www.chimediagroup.com); Bio-IT World (www.bio-itworld.com); eNewsletters; Lead Generation Programs (chimediagroup.com); Contact Us

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IND Submissions: A Primer

Table of Contents

Abstract