# Presentation: 894418

## Steve Wilson, DrPH, CAPT USPHS
Deputy Director, Division of Biometrics II, CDER/FDA

ICH Public Meeting
 April 22, 2005 
Doubletree Hotel and Executive Business Center
1750 Rockville Pike, Rockville, MD

*Deputy Director, Division of Biometrics II, CDER/FDA*
- ICH Public Meeting
-  April 22, 2005
- Doubletree Hotel and Executive Business Center
- 1750 Rockville Pike, Rockville, MD

- Guidance Compliant eCTDs*Module 4: Safety*

## Disclaimer

- Views expressed in this presentation are those of the speaker and not, necessarily, of the Food and Drug Administration

## Outline

- Module 4 -- Safety
- Continuing Education -- Questions and Answers(?)
- Final Exam

## CTD Introduction: Safety

**Module 4**
- Nonclinical
- Study Reports
- 4
- 4.1 T of C

## Module 4: Safety

- 4.2 Study reports
- 	4.2.1 Pharmacology
- 	4.2.2 Pharmacokinetics
- 	4.2.3 Toxicology
- 4.3 Literature references

## 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

## 4.2.1.1 Primary Pharmacodynamics

- Study report [identification number] and related information
*Legacy study report*
*Synopsis*
*Study report body*
*Protocol and amendments*
*Signatures of principal or coordinating investigator(s)  *
*Audit certifications and reports*

## 4.2.1.1 Primary Pharmacodynamics

*Documentation of statistical methods and interim analysis plans*
*Documentation of inter laboratory standardization methods of quality assurance procedures if used *
*Publications based on the study*
*Important publications referenced in the report *
*Compliance and/or drug concentration data *
*Individual subject data listings*

## 4.2.1.1 Primary Pharmacodynamics

- Data tabulation
*Data tabulation datasets*
*Data definitions*
- Data listing datasets
*Data listing datasets*
*Data definitions*
- Analysis datasets
*Analysis datasets*
*Analysis programs*
*Data definitions*
- IND safety reports

## 4.2.1.2 Secondary Pharmacodynamics

- Study report [identification number] and related information
*See  Primary pharmacodynamics Study report and related information for headings*

## Folder Structure of Module 4

## Granularity: Module 4 -- Safety

## 4.2 Study Reports

- 4.2.1 Pharmacology
- 4.2.2 Pharmacokinetics
- 4.2.3 Toxicology
***4.3 Literature references***

## Continuing EducationQuestions & Answers (?)

## Questions & Answers (?)– CTD

*M4: The CTD — General Questions and Answers *(October 2003)
- ... one in a series of guidances that provide recommendations for applicants preparing the Common Technical Document for the Registration of Pharmaceuticals for Human Use ( CTD) for submission to the U. S. Food and Drug Administration ( FDA).
- ... provides answers to questions that have arisen since the finalization of the harmonized CTD guidance documents in November 2000.
- ... addresses general questions about the CTD.
- Other question and answer ( Q & A) guidances ... quality, safety, and efficacy.
- The questions and answers provided here reflect the consensus of the ICH parties.

## Questions & Answers (?)– CTD/Safety

## Continuing Educationwww.fda.gov

## The Latest Newssort by date

## Questions & Answers (?) – CTDs & eCTDsYour Final Exam 

- Q10 Integrated Summary of Safety and Effectiveness
- Does the CTD section on safety in Module 2 replace the section under 21 CFR 314.50( d)( 5)( v)-( vi) calling for integrated summary of safety and effectiveness ( ISS/ ISE)?

## Questions & Answers (?) – CTDs & eCTDsYour Final Exam – Answer

- A10: The ISS/ ISE are critical components of the safety and effectiveness submission and are expected to be submitted in the application in accordance with the regulation.
- FDA’s guidance *Format and Content of Clinical and Statistical Sections of Application* gives advice on how to construct these summaries.
- Note that, despite the name, these are integrated analyses of all relevant data, not summaries.

## Questions & Answers (?) – CTDs & eCTDsYour Final Exam – Answer

- The Clinical Safety sections of the CTD follow approximately the outline of the sections of the ISS/ ISE, although they are somewhat modified by experience with ICH E-3 ( Structure and Content of Clinical Study Reports).
- The CTD Clinical Overview and Summary in Module 2 will not usually contain the level of detail expected for an ISS.
- It may contain the level of detail needed for an ISE, but this would need to be determined on a case- by- case basis.

## Questions & Answers (?) – CTDs & eCTDsYour Final Exam – Answer

- If the requirements of 21 CFR 314.50 can be met for a particular application by what is in the CTD Module 2 summary, the CTD Module 2 section would fulfill the need for an ISS/ ISE.
- In some cases, it will be convenient to write much of what is needed in the CTD Module 2 with appropriate appendices in Module 5.
- In other cases, the ISS/ ISE would be summarized in Module 2, with detailed reports in Module 5.
- Any questions about these matters can be raised with the reviewing division.

## Questions & Answers (?) – CTDs & eCTDsYour Final Exam

- Q3: Tables of Contents and Pagination
*For a paper CTD submission, the guidance states that for the comprehensive Table of Contents ( TOC) in Module 1, no page numbers should be used. Does this apply only to the TOC in Module 1, or for all TOCs in every module? Also, besides the volume numbers and tab identifiers, should the module numbers also be included? **For Modules 3, 4, and 5, should the volume number be part of the Table of Contents? *
- A3: There are no specific guidelines for the page numbers of the TOC. Module numbers, volume numbers, and tab dividers should be part of all TOCs
- What about eCTDs?

## Specifications

## Efficient Drug Development

## Watch This Space:ICH Terminology Standards -- Proposed M6

- Maintenance process for ICH Terminology Lists
- Objective
- Develop maintenance process to keep terminology lists in ICH guidances
- Status
- Concept paper accepted by steering committee
- Standard operating procedures being developed
- Pilot in 2005

## Proposed M6 Maintenance Process

- Collect change requests
- Evaluate change requests
- Decision process
- Maintain terminology lists and codes
- ICH web site
- NCI Enterprise Vocabulary Services

## THANK YOU

- (301) 827-5583
- wilsons@cder.fda.gov