ICH Q8(R2) guideline describes the suggested contents for the Module 3 Quality

3.2.P.2 (Pharmaceutical Development) section of a regulatory submission in the ICH

M4 Common Technical Document (CTD) format.
ICH M4 Organization of the CTD

• Module 1. Administrative Information and Prescribing Information

• Module 2. Common Technical Document Summaries

• Module 3. Quality

• Module 4. Nonclinical Study Reports

• Module 5. Clinical Study Reports

ICH Q8 、 Q9 、 Q10
 Pharmaceutical development

• Components of Drug Product

- API’s physical, chemical, biological properties and risk assessment
- Excipients
• Drug Product
- Formulation development
- Overages
- Physicochemical and Biological properties
• Manufacturing Process Development
• Container Closure System
• Microbiological Attributes
• Compatibility
Quality by Design (QbD)
• Identification of the product attributes that are important to safety and efficacy.
• The linkage of those material attributes that can impact the desired product
attributes.
• The design of the process to meet all critical attributes.
• The delineation of a proper control strategy to ensure consistent process
performance.
• Validation demonstrating the effectiveness of the control strategy.
• Ongoing monitor and review to ensure the desired process performance
throughout the entire product lifecycle.
Elements that underpin QbD are:
• Quality Target Product Profile (QTPP)
• Critical Quality Attributes (CQAs)
• Risk Assessment
(linking material attributes and process parameters to product CQAs)
• Design Space
• Control Strategy
• Product lifecycle management and Continual improvement

Prior knowledge Design of Experiment

(DoE)
Risk Assessment Process Analytical Technology (PAT)
• Analysis of the Reference Listed Drug (RLD) Product
- Clinical
- Pharmacokinetics
- Drug release
- Physicochemical characterization
- Composition
• Quality Target Product Profile (QTPP) for the ANDA Product
• Dissolution Method Development and Bioequivalence Studies
• Components of Drug Product
- API’s physical, chemical, biological properties and risk assessment
- Excipients
• Drug Product
- Initial risk assessment
- Formulation and prototype development
- Updated risk assessment
• Manufacturing Process Development
- Initial risk assessment
- scale-up from lab to commercial scale
- Updated risk assessment
• Container Closure System
• Microbiological Attributes
• Compatibility
• Control Strategy
- Product lifecycle management and continual improvement
 Critical Quality Attributes (CQAs)

Critical process parameters (CPPs)

Multiple unit particle/pellet system (MUPS)
The tablets were sampled after the press was run at the steady state of the specified DOE run
conditions for at least five minutes. Pre-compression force and press speed did not affect
tablet hardness within the range studied. There was no interaction between these three
parameters. The main effects plot was that an increase in main compression force resulted in
an increase in tablet hardness. The compression force was specified at 7.0-11.0 kN,
corresponding to the hardness range of 4.7-10.6 kP.
Elements that underpin QbD are:
• Quality Target Product Profile (QTPP)
• Critical Quality Attributes (CQAs)
• Risk Assessment (linking material attributes and process parameters to product
CQAs)
• Design Space
• Control Strategy
• Product lifecycle management and Continual improvement

Prior knowledge Design of Experiment

(DoE)
Risk Assessment Process Analytical Technology (PAT)