Document Reuse: Theory and Practice Peggy Boe, RN Sr. Director, Medical Writing Image Solutions, Inc (ISI) Company logo here
Best Practice: Single Sourcing Creating reusable text and information Requires careful consideration of which documents contain similar/same text or data Submitting as IND in ectd format maximizes this best practice efficiency
21 CFR 312.23 Item 5: IB CMC Nonclinical Clinical
ICH E6 GCP: Section 7 Purpose: To document that relevant and current scientific information about the investigational product has been provided to the investigator 1. Summary 2. Introduction 3. Physical, chemical, and pharmaceutical properties and formulation 4. Nonclinical studies 4.1 Nonclinical pharmacology 4.2 Pharmacokinetics and product metabolism in animals 5. Effects in humans 5.1 Pharmacokinetics and product metabolism in humans 5.2 Safety and efficacy 5.3 Marketing experience 6. Summary of data and guidance for the investigator This outline includes the minimum information that should be included (ICH E6: 7.1).
Who Reads the IB? Investigators and other study participants p (ICH E6: 4.1.2, 5.6.2) IRBs (ICH E6: 3.1.2, 4.4.2) Food and Drug Administration (FDA) Medical Writers
IB Content Presentation Concise Simple Objective Balanced Non-promotional GOAL: Enable a clinician or potential investigator, IRB, and FDA to understand it and make unbiased risk-benefit assessment of the appropriateness of the proposed trial
What Are the Source Documents? 1. Drug / Clinical Development Plan (DDP or CDP) 2. Target Product Profile (TPP) 3. Literature search 4. Chemistry, Manufacturing, and Control (CMC) documents 5. Nonclinical Study Reports 6. Protocols 7. Clinical Study Reports
beginning with the goal in mind TPP template developed by FDA-PhRMA working group Target (Language that the sponsor hopes to achieve) Annotations (Summary information regarding completed or planned studies) Comments (To provide clarity) Links each specific labeling concept to a specific study or other source of data Source: Jeanne M. Delasko, FDA. DIA Annual Conference, FDA Labeling Update. 28 June 2005
Template Example
Appendix C: Template
TPP Format Labeling Format* 1. Indications and Usage 2. Dosage and Administration 3. Dosage Forms and Strengths 4. Contraindications 5. Warnings and Precautions 6. Adverse Reactions 7. Drug Interactions Highlights of Prescribing Information Full Prescribing Information: Contents Full Prescribing Information 1. Indications and Usage 2. Dosage and Administration 3. Dosage Forms and Strengths 4. Contraindications 5. Warnings and Precautions 6. Adverse Reactions 7. Drug Interactions 8. Use in Specific Populations 8. Use in Specific Populations 9. Drug Abuse and Dependence 9. Drug Abuse and Dependence 10. Overdosage 10. Overdosage 11. Description 11. Description 12. Clinical Pharmacology 12. Clinical Pharmacology 13. Nonclinical Toxicology 13. Nonclinical Toxicology 14. Clinical Studies 14. Clinical Studies 15. References 15. References 16. How Supplied/Storage and Handling 17. Patient Counseling Information 16. How Supplied/Storage and Handling 17. Patient Counseling Information *Draft guidance January 2006
Traditional IND or ectd IND? CTD Guidance: US Module 1 Regional Information Source: FDA ectd Comprehensive Table of Contents Headings and Hierarchy, 2005-07-06
Target Product Profile 3. Dosage Forms and Strengths 11. Description 16. How Supplied/Storage and Handling Investigator s s Brochure Table of Contents List of Abbreviations 1. Summary 2. Introduction 3. Physical, chemical, and pharmaceutical properties and formulation H dli 4. Nonclinical studies 6. Adverse Reactions 7. Drug Interactions 8. Use in Specific Populations 9. Drug Abuse and Dependence 10. Overdosage 12. Clinical Pharmacology 14. Clinical Studies 4.1 Nonclinical pharmacology 4.2 Pharmacokinetics and product metabolism in animals 4.3 Toxicology 5. Effects in humans 51Ph 5.1 Pharmacokinetics and product metabolism in humans 5.2 Safety and efficacy 5.3 Marketing experience 6. Summary of data and guidance for the investigator
Nonclinical Text & Data Organization Order study summaries as they appear in the Module 2.6 Written Summaries and Module 4 Species Route Duration Reuse the 2.6 Tabulated Summaries in the IB
Target Product Profile Investigator s s Brochure 1. Indications and Usage Table of Contents List of Abbreviations 2. Dosage and Administration 1. Summary 3. Dosage Forms and Strengths 2. Introduction 4. Contraindications 3. Physical, chemical, and 5. Warnings and Precautions pharmaceutical properties and formulation 6. Adverse Reactions 4. Nonclinical studies 7. Drug Interactions 4.1 Nonclinical 8. Use in Specific Populations pharmacology 9. Drug Abuse and Dependence 4.2 Pharmacokinetics and 10. Overdosage product metabolism in animals 11. Description 4.3 Toxicology 12. Clinical Pharmacology 5. Effects in humans 13. Nonclinical Toxicology 51Ph 5.1 Pharmacokinetics and 14. Clinical Studies product metabolism in humans 15. References 5.2 Safety and efficacy 16. How Supplied/Storage and Handling 5.3 Marketing experience 17. Patient Counseling Information 6. Summary of data and guidance for the investigator
IB Updates Typical scenario Add all new material Do it as fast as you can Consider a redact
Step #1: Revise Existing Content Restructure nonclinical if it doesn t mimic 2.6 Delete irrelevant data (fun!) Check source docs for accuracy and thoroughness in IB Check IB text for additional data to be included in tables Delete text redundant with tables Rewrite/summarize key messages from data interpretation
Step #2: Add New Content Acquire newly released study reports or updated summaries Determine appropriate location (subset reports) Populate the tables with new data Make sure any new authors understand the goals for structuring with the CTD in mind Keep any new text to a concise minimum
Investigator s Brochure Labeling Format 1. Summary 1. Indications and Usage 2. Introduction 2. Dosage and Administration 3. Physical, chemical, and 3. Dosage Forms and Strengths pharmaceutical properties 4. Contraindications and formulation 5. Warnings and Precautions 5. Effects in humans 7. Drug Interactions 6. Summary of data and 8. Use in Specific Populations guidance for the investigator 9. Drug Abuse and Dependence 10. Overdosage 11. Description 12. Clinical Pharmacology 13. Nonclinical Toxicology 14. Clinical Studies 15. References 16. How Supplied/Storage and Handling 17. Patient Counseling Information
IND Case Study: Lessons Learned Compiling the IND should not be a lastminute effort Nonclinical study reports should be organized and data captured in a reusable format ongoing process Writing sequence is key to best efficiency 1. Literature search 2. Nonclinical summaries 3. IB 4. Protocol Establish review processes, stylistic issues, templates, version control very early
Marketing Applications Lessons Learned Plan for your marketing application from the start of your product development program Develop strategic relationships with professional writers who can help keep your growing library of documents consistent, t organized Use tools available to you to maintain i (or adjust) the key messages from IND all the way to the marketing label
Conclusions Drug development should begin with the end in mind Medical Writers should be involved in most regulatory documents Single-sourcing text/data is necessary for best efficiencies i i The ectd IND maximizes that efficiency Start early if you want to change over from paper to ectd At the very least, do begin now creating your submission i using CTD structure
Questions?