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 – Do all Authorities Expect the Same?
- Differences between the expectations of health authorities
- Consequences in case of changes
- 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
- How to control impurities in a starting material
- Analytical techniques
- Optimisation of chromatographic methods
- Downstream experiments
- Validation of analytical procedures
- Qualification of Starting Materials
How to Audit Starting Material Manufacturers
- Impact of ICH Q7 Q&A and ICH Q11 on auditing Starting Material manufacturers
- Health Authority and Regulatory expectations
- Risk based approach on “How to “ audit Starting Materials
- Development and use of the APIC guideline on auditing Starting Materials
- Practical examples and case studies