Preparing the CMC Section for NDAs/CTDs/INDs

This course is designed for personnel involved in preparing the chemistry, manufacturing and controls (CMC) section of a NDA or IND in CTD format. Note that the course does not cover a BLA, which is for biologics. However, personnel who are not involved in CMC document preparation but want an overall understanding of what is involved for both the drug substance and drug product will also benefit from the course.

Learning Objectives

This course provides participants with a thorough understanding of the requirements for each CMC section of the Common Technical Document (CTD), i.e., the format to be used for NDAs. Additionally, the course will suggest ways to streamline the preparation of CMC documents, present techniques for making the CMC submission easy to review, and discuss how to address issues during CMC meetings with the FDA.

Course Description

This course includes an overview of the International Conference on Harmonization (ICH) process and the organization of the CTD, detailed information and discussions related to each element required in the drug substance and drug product sections of NDAs, and an outline of what is required in the drug substance and drug product sections of INDs. The course emphasizes the requirements related to drug substance starting materials, drug substance and drug product specifications, impurities and stability, and pharmaceutical development reports. It will also discuss the use of Drug Master Files (DMF) and comparability protocols.

________________________________________

COURSE AGENDA

DAY ONE

ICH Process and CTD Organization

 ICH Background/Working Groups
 ICH 5-Step Process
 CTD Modules

Requirements for Drug Substance

 S.1 General Information: Nomenclature, Structure, General Properties
 S.2 Manufacture
- Manufacturers
- Flow diagram
- Description of Manufacturing Process and Process Controls
 Reprocessing, Rework, Recovery of Solvents, Recycling
 Types of Process Controls
- Control of Materials
 Starting Materials
• Requirements
• Justification for starting materials
 Reagents, Solvents, Auxiliary Materials
- Control of Critical Steps and Intermediates
 Justification for Critical Controls
 Types of Intermediates
- Manufacturing Process Development
 S.3 Characterization
- Elucidation of Structure
- Other Characteristics: Potential for Isomerism and Solid-state Forms
- Impurities
 Organic, Inorganic, Residual Solvents
 Specified, Unspecified, Identified, Unidentified
 S.4 Control of the Drug Substance
- Specifications
- Analytical Procedures
- Validation of Analytical Procedures
- Batch Analyses
- Justification for Specifications
 S.5 Reference Standards
 S.6 Container Closure System
 S.7 Stability
- Protocol, Data Evaluation
- Photostability
- Forced Degradation/Stress Testing

Drug Master Files (DMF)

 What are they
 Types of DMFs
 When should they be used
 How do you use them
 Obligations of DMF holder vs. NDA holder
 Information in a DMF vs. NDA

DAY TWO

Requirements for the Drug Product

 P.1 Description and Composition
 P.2 Pharmaceutical Development
- Drug Substance
- Excipients
- Formulation Development
- Manufacturing Process Development
- Overage vs. Overfill
- Container Closure Suitability
 P.3 Manufacture
- Manufacturer
- Batch Formula
- Description of Manufacturing Process and Process Controls
- Control of Critical Steps and Intermediates
- Process Validation and/or Evaluation
 P.4 Control of Excipients
- Specifications
- Novel excipients
 P.5 Control of the Drug Product
- Specifications: Release, Stability, In-house
- Analytical Procedures
- Validation of Analytical Procedures
- Batch Analyses
- Justification of Specifications
 P.6 Reference Standards
 P.7 Container Closure Systems
- Primary, Secondary, Functional and Non-Functional Secondary Packaging
 P.8 Stability
- Protocol, Data Evaluation
- Photostability
- Forced Degradation/Stress Testing

Regional Information

 Executed Batch Records
 Comparability Protocols
 Method Validation Package

Impurities

 Types of Impurities
 Specified vs. Unspecified
 Identification/Qualification/Reporting Thresholds
 Qualification
 Residual Solvents

INDs
 Drug Substance Information for Phase 1 and Phase 2 INDs
 Drug Product Information for Phase 1 and Phase 2 INDs

General Question and Answer Session