Ann: Appendix 4C & Quarterly Update, page-5

Hi NZ, this may help.

Under FDA rules for clinical trials, a company does not necessarily need to have all the pills manufactured prior to starting a Phase 2/3 trial. Instead, they are required to show that they have the manufacturing processes in place to ensure the production of the investigational drug with consistent quality, purity, and strength. Here's a breakdown based on the information available:

• Phase 2 and Phase 3 Trials: These phases require more stringent controls on manufacturing processes because they involve a larger number of participants and are crucial for establishing the drug's effectiveness and safety profile on a broader scale. The company needs to demonstrate that the drug can be produced consistently across batches. This involves:
  
  
  • Providing detailed specifications of starting materials.
  • Outlining process controls to assure quality, purity, and consistency throughout production.
  • Detailing stability data and batch records to establish reproducibility of manufacturing processes.
  • Describing the manufacturing facility, quality control unit, and their responsibilities.
  • Reporting any changes in drug substance, drug product, or manufacturing processes to the FDA in a timely manner, alongside supporting data if necessary.
• Chemistry, Manufacturing, and Controls (CMC) Information: For these phases, the FDA requires a comprehensive CMC section in the Investigational New Drug (IND) application. This section should include information on the drug substance and drug product, their characterization, specifications, and the processes used to manufacture them. The focus is on ensuring that the drug can be manufactured in a way that supports the trial's objectives, ensuring participant safety and data reliability.
• Good Manufacturing Practices (cGMP): Compliance with current Good Manufacturing Practices (cGMP) is mandatory. While Phase 1 drugs might have some exemptions, Phase 2 and 3 drugs are generally subject to full cGMP regulations, emphasizing the need for a well-documented and controlled manufacturing process.
  

Therefore, while having a supply of pills ready is beneficial for immediate trial needs, the critical aspect from an FDA perspective for Phase 2/3 trials is demonstrating that robust manufacturing processes are in place to produce the drug consistently throughout the trial duration. This ensures that the drug's quality remains uniform, which is essential for the validity of clinical trial results.