2018 503B Smoke Study Issues

In the first 6-months of 2018, fiftteen 503B Outsourcing Facilities were cited for smoke study issues.  Airflow is critical in maintaining sterile conditions, as described in the FDA Guide on Aseptic Processing

In an aseptic process, the drug product, container, and closure are first subjected to sterilization methods separately, as appropriate, and then brought together. Because there is no process to sterilize the product in its final container, it is critical that containers be filled and sealed in an extremely high-quality environment (p. 2)

Proper design and control prevents turbulence and stagnant air in the critical area. Once relevant parameters are established, it is crucial that airflow patterns be evaluated for turbulence or eddy currents that can act as a channel or reservoir for air contaminants (e.g., from an adjoining lower classified area). In situ air pattern analysis should be conducted at the critical area to demonstrate unidirectional airflow and sweeping action over and away from the product under dynamic conditions. The studies should be well documented with written conclusions, and include evaluation of the impact of aseptic manipulations (e.g., interventions) and equipment design. Videotape or other recording mechanisms have been found to be useful aides in assessing airflow initially as well as facilitating evaluation of subsequent equipment configuration changes. It is important to note that even successfully qualified systems can be compromised by poor operational, maintenance, or personnel practices (p. 6) [Bold added by author].

A review of the posted 483 reports identified the following smoke study issues:

  • 47% of the citations observed reported a lack of smoke study tests under dynamic conditions.
  • 47% of the citations identified incomplete smoke studies (not all compounding areas were tested), studies that did not accurately reflect firms aseptic practices (less than the maximum number of operators, video recordings that did not match observed aseptic practices, studies where not all equipment and component configurations were tested, where the most complicated or challenging configuration was not tested, were the test setup and aseptic operations did not match actual practice, the smoke used was faint an intermittent, and lastly where the study did not include the transfer of starting components and materials, or in-process material, or transfer of product into the final container within the ISO-5 area).
  • 13% of the citations reported no visual recording of the smoke studies.
  • 13% of the citations identified smoke study failures. In one case the smoke was not moving at the same speed and direction with no or minimal cross-over of streams to aseptic processing surface, in another case the airflow between the ISO 7 area and the anteroom appeared neutral.

Performance Validation has over 5,500 hours of combined experience performing smoke study testing and have completed over 30 Smoke Study projects ranging from a single hood to a complete aseptic filling facility.  Have a question on Smoke Studies, need to resolve smoke study issues, or need to schedule your next study?  Contact Dalton Pierson Performance Validation’s Smoke Study Expert, or use our Contact us form and we will be happy to assist you with your Critical Airflow testing.