How to define API Regulatory Starting Materials: What do the Guidelines tell us?
- API Regulatory Starting Materials – overview of guidelines
- Definition according to the guidelines
- Global guidelines (ICH Q7 and Q11)
- US, EU and Japan guidance
- How to use the term “significant structural fragment”
- Distinguishing starting materials from raw materials, reagents and solvent
- Selection of an appropriate Starting Material
- Starting Material specification
API Regulatory Starting Materials – Challenges and practical Implications for a Submission
- How to use the elements of the guidelines in practice?
- Is a global approach the best way forward?
- What is the level of detail to be provided?
- What are the consequences of the choice?
API Regulatory Starting Materials – What is different for Generics?
- One file fits all?
- Redefinition of the RSM; practical aspects
- Practical experiences
Starting Materials and the CEP Application Procedure
- Regulatory background
- Scope of the CEP procedure
- Provisions of the Guideline PA/PH/CEP (14) 06 “Use of a CEP to describe a starting material in an application for another CEP“
- Important points to be considered for defining an API starting material
How to handle post-approval Changes
- Changes to the pre-starting material information
- Re-definition of the starting material: possible or not
- Handling changes/variations when multiple stakeholders are involved
From Starting Materials to APIs: Risk Assessments and criticality Analyses
- Criticality analysis methods (HAZOP, FMEA etc)
- Critical quality attributes (CQA) and critical process steps CPS)
- Linking CQA and synthesis steps
- Critical impurities
- Critical raw materials
- Process criticality analysis; example
- API synthesis: How to define suitable Starting Materials
- How to defend the choice of the Starting Material in the submission
Appropriate Controls for Starting Materials Manufacturers
- How to control impurities in a starting material
- Analytical techniques
- Optimisation of chromatographic methods
- Downstream experiments
- Validation of analytical procedures
- Qualification of Starting Materials
APIC’s Position on Starting Materials
- Definition of the SM
- Risk management
- Qualification of the SM supplier
- Pre-SM information
- Handling changes/variations