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Breakout Session:
Integrating CMC Review and Inspection

Summary of Stakeholder Comments
 (posted 5/19/2003)

Integrated CMC Review and Inspection Session: Discussion Topics

Discuss the following topics based with the primary focus on streamlining and optimizing the overall regulatory review and inspection processes. Your feedback is important and will be used by the Agency in developing the drug quality system for the 21^st century.

1. Documentation

• The CTD-Q already provides a placeholder for a section (3.2.P.2) on pharmaceutical development studies which would include discussions and data on key quality attributes in the design and manufacture of the drug substance and drug product and any critical tests and controls that have been established to assure product quality and consistency. What information should be included in this section to facilitate reviewer understanding of your critical processes and controls?
• · What would be the benefits of including additional scientific information in the dossier to help the reviewer gain a more thorough understanding of the key process parameters for the product including the critical elements and risks associated with the drug substance and drug product manufacturing process and controls?
  
  
• What risks might be associated with providing this information? How could the review of this information be structured to alleviate these risks?

2. Interim specifications and Continuous Process Improvement

The concept of the establishment of interim specifications at the time of approval has been raised (ICH Q6A and FDA Draft Drug Product Guideline).

• What would you propose as a process for establishing and finalizing interim specifications within the context of an optimized review and inspection process?
  
  
• How would you evaluate the risks and benefits associated with the use of interim specifications and continuous improvement concepts during initial commercialization stages resulting in optimization of manufacturing process and the development of final specifications?

3. Inspections

In consideration of Drug Quality Systems for the 21^st Century with enhanced documentation and demonstration of the scientific understanding of manufacturing process and controls, we should consider what role inspections could play in this integrated approach.

• What is the most effective role of inspections? Would there be value in having a highly trained pharmaceutical inspectorate focused mainly on inspections of pharmaceutical facilities? If yes, what should their role be?
  
  
• Is the PAI program still relevant in this integrated approach or has it outlived its usefulness? Should the PAI be eliminated?
  
  
• In what instances might inspections (or segments of inspection) conducted prior to approval of an application be warranted?

4. Product and Technology Specialists

FDA has proposed the use of product or technology specialists as part of the inspection process to facilitate and bridge the review and inspection process.

• What are the benefits of including highly trained specialists within the inspection and review process? How would you define the roles of these specialists (e.g., during review, on inspection teams, etc.)? How would the inclusion of specialists facilitate the introduction of new technologies such as Process Analytical technology (PAT)?
  
  
• What skill sets and technical backgrounds should the specialists have (e.g., organic chemistry, analytical chemistry, pharmaceutical science, pharmacy, chemical engineering, microbiology, statistics)?
  
  
• What areas might be better reviewed on site with direct access to manufacturing information vs. those areas that can be adequately reviewed by the registration dossier? How should the specialist and field investigator be optimally deployed?
  
  
• What are your experiences with "Team BIO"? What "lessons learned'" can be shared from previous inspections jointly conducted by reviewers (or specialists) and field investigators?

5. Next Steps

• What are the next steps necessary to develop these programs including future workshop topics? If as a next step, we could only work on one of the above topics, what should it be?

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