Here are the references to relevant guidelines from the EMA and FDA for your CMC strategy questions:

1. Formulation and Active Ingredient:

• According to the European Medicines Agency (EMA) guidelines, the identity and purity of the active ingredient should be clearly defined and validated. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)
• For unexpected findings related to the stability of the formulation, the EMA provides flexibility to address these challenges, especially for pandemic preparedness. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)

2. Manufacturing Process Optimization:

• The EMA emphasizes the need for successful optimization of the manufacturing process for Phase 1 and 2 trials. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)
• Any changes made to the manufacturing process should be well-documented and validated as per EMA guidelines. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)

3. Raw Material Supply Chain:

• According to the EMA, any issues with the supply chain during Phase 1 and 2 trials should be addressed, and the documentation should be comprehensive, including contingency plans and risk assessments. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)

4. Analytical Methods and Specifications:

• The EMA recommends that analytical methods be validated and adjustments made based on Phase 1 and 2 learnings. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)
• Additional specifications or analytical tests needed for MAA submission should align with EMA guidelines. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)

5. Stability Studies:

• Stability studies insights gained during Phase 1 and 2 should align with EMA guidelines. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)
• Any unexpected stability issues arising from these studies should be addressed and mitigated, as per EMA guidelines. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)

6. Regulatory Compliance and Documentation:

• The CMC strategy should align with regulatory expectations during Phase 1 and 2, as emphasized by the EMA guidelines. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)
• Any regulatory inspections or audits should be managed in line with EMA guidelines for pharmaceutical vaccine development. (Reference: EMA guidelines for pharmaceutical vaccine CMC strategy)

You can also refer to the U.S. Food and Drug Administration (FDA) guidelines for additional insights into these aspects.

Sources

Multidisciplinary: vaccines | European Medicines AgencyGuidance for medicine developers and other stakeholders on COVID-19Risk-Based Biologics: CMC Flexibilities in the EU Regulatory SystemCMC Strategies and Advanced Technologies for Vaccine Development to Boost Acceleration and Pandemic Preparedness - PMC - NCBIConsiderations for the chemistry, manufacturing and Controls (CMC) - quality package for COVID-19 vaccines- interim lessons learnt by the European medicines Agency (EMA) - PMC[PDF] COVID-19 biologics- Procedural aspects and quality scientific considerations in the context of the crisis- EMA perspective - CASSS

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