Chemistry Manufacturing and Controls Flashcards
What is CMC
The information describing the composition, manufacture and control of the drug substance and drug product
Are there CMC sections in both IND and NDA
yes
What can be found in the CMC
Identity/Composition/Formulation
DP = DS + Excipient
Strength
Drug Substance (DS) can be quantitatively assayed in the Drug Product (DP)
Quality
Analytical test procedures and acceptance criteria are indicative of product quality
Batch to batch variations are minimized by compliance with cGMP
Purity
Assay to determine
Purity of DS
Purity of DS in DP
Impurity profile of the DS
Stability program
Stability Data
Sufficient to cover clinical trial (Phase I)
Labeling (Caution statement …)
Evaluation of Manufacturing process
Process flow diagram
Formulation
Sterilization
Validation
CMC and Controls in CTD
Module 2
2.3 Quality Overall Summary (QOS)
Module 3
3.1 Table of Contents
3.2 Body of Data
3.3 Literature References
3.2 Body of Data
3.2 S -Drug Substance (DS) Section
3.2 P -Drug product (DP) Section
3.2 A -Appendices
3.2 R -Regional Information
Module 3.2 S Drug Substances section have in it
3.2.S.1 General Information
3.2.S.1.1 Nomenclature
3.2.S.1.2 Structure
3.2.S.1.3 General Properties
3.2.S.2 Manufacturer
Name and full address of facilities and testing laboratories
Function and Responsibilities
3.2.S.3 Characterization
3.2.S.4 Control of Drug Substance (Active Ingredient)
3.2.S.4.1 Specification
3.2.S.4.2 Analytical Procedures
3.2.S.4.3 Validation of Analytical Procedures
3.2.S.4.4 Batch Analysis (COA)
3.2.S.4.5 Justification of Specification
3.2.S.4.6 Reference Standards
3.2.S.4.7 Container Closure System
3.2.S.4.8 Stability
Stability Summary and Conclusions
What does 3.2P. Drug Product section intail
3.2.P.1 Description and Composition
Unit composition
Inactive ingredients and amount
3.2.P.2 Pharmaceutical Development
Report
3.2.P.3 Manufacture
3.2.P.3.1 Manufacturer(s)
Name and full address of facilities and testing laboratories
Function and Responsibilities
cGMP Certification
3.2.P.3.2 Batch Formula
3.2.P.3.3 Description of Manufacturing Processes and Process Controls
Master Production Batch Record
If sterile product-Aseptic fill/Terminal sterilization
Reprocessing statement
3.2.P.3.4 Controls of Critical Steps and Intermediates
3.2.P.3.5 Process Validation and/or Evaluation
Microbiological sterilization validation
Filter validation (if aseptic fill)
3.2.P.4 Control of Excipients
3.2.P.4.1 Specifications
Testing specifications- identification and characterization
Supplier’s COA
3.2.P.4.2 Analytical Procedures
3.2.P.4.3 Validation of Analytical Procedures
3.2.P.4.4 Justification of Analytical Procedures
3.2.P.5 Control of Drug Product
3.2.P.5.1 Specifications
3.2.P.5.2 Analytical Procedures
3.2.P.5.3 Validation of Analytical Procedures
3.2.P.5.4 Batch Analysis
3.2.P.5.5 Characterization of Impurities
3.2.P.5.6 Justification of Specification
3.2.P.6 Reference Standards
3.2.P.7 Container Closure
Summary of Container Closure System
Components Specification and Test Data
Packaging Configuration and Sizes
Container/Closure Testing
Source of Supply and Suppliers Address
3.2.P.8 Stability
3.2.P.8.1 Stability Summaries and Conclusion
Stability Protocol & Expiration Dating Period
3.2.P.8.2 Post-approval Stability
Protocol and Commitments
3.2.P.8.3 Stability Data
Normal and accelerated condition, min 3 month
Batch numbers on stability records the same as the test batch
3.2.A. Appendicies
3.2.A.1 Facilities and Equipment
3.2.A.1 Adventitious Agents
Materials of Animal Origin & Safety Evaluation
3.2.A.1 Novel Excipients
3.2.R Regional Information
Executed Batch Records (USA only)
Method Validation Package (USA only)
Comparability Protocols (USA only)
Process Validation Scheme for the Drug Product (EU only )
What should be done to Maintain CMC after Filling
CMC development
Continues in parallel with clinical development all the way through to License Application Submission
Simultaneously running activities
Scale-up
Validation
Stability
Formulation improvements
Container closure evaluation and many more
Successfull CMC
Knowledgeable RA and QC & QA staff
Excellent document management system
Consistency of the overall flow and nomenclature
Be prepared for questions
