Tag: process controls

FDA Draft Guidance on “Considerations for Complying with 21 CFR 211.110”

Usually I expect the FDA to publish some basic primer material as a webinar, so I was a little surprised when “Considerations for Complying With 21 CFR 211.110” was recently published as a draft. I’ve been rereading it, looking for what is actually worthy of a guidance here, and quite frankly, struggling.

It literally is a refresher course on 21CFR211.110. Maybe I should read it as “No we were serious about ICH Q8 and critical quality attributes.” Or maybe it is just the result of one too many bad Type C meetings lately.

Anyway, good refresher on product quality, in-process controls and samples. Still I think this would be better as a webinar with some graphics. Maybe I’ll better understand why this was published based on what sort of crazy comments are made and I can scratch my head and wonder what shenanigans some of these companies are up to.

Risk Management for the 4 Levels of Controls for Product

There are really 4 layers of protection for our pharmaceutical product.

  1. Process controls
  2. Equipment controls
  3. Operating procedure controls
  4. Production environment controls

These individually and together are evaluated as part of the HACCP process, forming our layers of control analysis.

Process Controls:

    • Conduct a detailed hazard analysis for each step in the production process
    • Identify critical control points (CCPs) where hazards can be prevented, eliminated or reduced
    • Establish critical limits for each CCP (e.g. time/temperature parameters)
    • Develop monitoring procedures to ensure critical limits are met
    • Establish corrective actions if critical limits are not met
    • Validate and verify the effectiveness of process controls

    Equipment Controls:

      • Evaluate equipment design and materials for hazards
      • Establish preventive maintenance schedules
      • Develop sanitation and cleaning procedures for equipment
      • Calibrate equipment and instruments regularly
      • Validate equipment performance for critical processes
      • Establish equipment monitoring procedures

      Operating Procedure Controls:

        • Develop standard operating procedures (SOPs) for all key tasks
        • Create good manufacturing practices (GMPs) for personnel
        • Establish hygiene and sanitation procedures
        • Implement employee training programs on contamination control
        • Develop recordkeeping and documentation procedures
        • Regularly review and update operating procedures

        Production Environment Controls:

          • Design facility layout to prevent cross-contamination
          • Establish zoning and traffic patterns
          • Implement pest control programs
          • Develop air handling and filtration systems
          • Create sanitation schedules for production areas
          • Monitor environmental conditions (temperature, humidity, etc.)
          • Conduct regular environmental testing

          The key is to use a systematic, science-based approach to identify potential hazards at each layer and implement appropriate preventive controls. The controls should be validated, monitored, verified and documented as part of the overall contamination control strategy (system). Regular review and updates are needed to ensure the controls remain effective.