Preparing the Common Technical Document (CTD) for CMC

Table of Contents

CHAPTER 1: INTRODUCTION

• Scope of this Guide
• Brief History of US Drug Regulation
  • Drug Regulatory Law
• Drug Approval
  • Biologic Products
• The International Conference on Harmonization

CHAPTER 2: THE CTD FORMATTED IND

• The CTD Format
• Preparing the CMC Sections of the CTD
• Preparing the CMC Sections of the CTD
  • Module 2: Common Technical Document Summaries
  • Module 3: Quality
• CMC Topic Coverage
• Formulating a Strategy
• CMC Requirements for Biopharmaceuticals
  • Step One-Which FDA Center is involved
  • Step Two-Establishing a time line
  • Step Three-Think like a Regulator

CHAPTER 3: ELEMENTS OF CGMP REGULATIONS

• Quality Assurance in Drug Manufacturing & Testing
• What are Standard Operating Procedures?
• Guide to Writing SOPs

CHAPTER 4: ASSAY DESIGN

• Introduction ...
  • Definitions
  • Assays and Analytes
  • Qualitative and Quantitative
• Drug Development and Manufacturing
  • Impurities
  • Therapeutics
• Universal Considerations
  • Precision
  • Time
  • Washing
  • Other Sources of Non-reproducibility
  • Repeatability between Labs
  • Optimal Reagent Amounts
  • Serial Dilutions
  • Standard Curves
  • Linearity
• Data Analysis
  • Multiplicity
  • Signal-to-background and Signal-to-noise Ratios
  • Z-prime
• Nature of Analyte and Matrix
  • Analyte Stability
  • Microbial Contamination
  • Metabolic Processes
  • Intractable Stability Problems
  • Separation and Enrichment
  • Internal Standard “Spike”
• Assay Objectives
  • Research, Development, or Process
  • Scalability
  • Sensitivity
  • Error Tolerance
• Assay Validation
  • validation
• Installation and Operation Qualification
  • Instruments and Equipment
• Assay Optimization
  • Factorial Design
  • Other Variables
• Performance Qualification
  • Instruments and Consumables
  • Operation Re-certification
  • Assay Parameters
  • Data Certification
• Checklist for General Assay Development
  • General
  • Sample
  • Data
• Standard Checklist To Be Used for Any Assay Development
  • Statistics Review
  • Correlation Coefficient
  • Standard Deviation
  • Coefficient of Variance
  • Z' Factor
  • More Complicated Statistics
  • Error Detection
  • Error Correction
  • Normalization and Data Condensing
  • Data Standardization
  • Statistical Analysis

APPENDIX 1: NEW DRUGS, SEC. 505

APPENDIX 2: SECTION LIST OF 21CFR 211

APPENDIX 3: QUALITY SYSTEMS APPROACH TO PHARMACEUTICAL CGMP REGULATIONS

TABLE OF EXHIBITS

• Exhibit 2.1 Diagrammatic Representation of the ICH Common Technical Document
• Exhibit 2.2 IND Process and Review Procedures of the CDER, Manual of Policies and Procedures - MAPP 6030.1
• Exhibit 3.1 The Drug Development Pathway
• Exhibit 3.2 What is Quality Assurance?
• Exhibit 4.1 Major Assay Design Considerations and Potential Problems Addressed
• Exhibit 4.2 Common Causes of Assay Non-reproducibility
• Exhibit 4.3 Sample Standard Curve with Data Interpolation, Extrapolation
• Exhibit 4.4 Parameters for the Validation of Different Types of Analytical Method
• Exhibit 4.5 Example of Factorial Design
• Exhibit 4.6 Ordered Steps for Quality Control of UHT Data