4.1 EudraLex GMP Guidelines requires “personnel available with appropriate training and experience in microbiology, sterility assurance, and knowledge of the processes to support the design of the manufacturing activities,” therefore, an appropriate subject matter expert should have direct oversight of airflow studies including management review of any airflow deficiencies, and determination where redesign of manipulations or equipment is needed with appropriate justifications. Demonstration of proper airflow over critical areas in aseptic manufacturing is required per EudraLex GMP Guidelines and requires that the maintenance (of unidirectional airflow) should be demonstrated and qualified. The FDA Guidance for Industry (2004) recommends smoke studies as a tool for airflow qualification.

4.2 The visualization of airflow is subjective, and it is not possible to eliminate all turbulence in dynamic (in operation) cleanrooms. The focus of the smoke study is to show that airflow is in control and turbulence is minimized. Airflow studies are used to demonstrate that the critical zone is protected. They are also useful to determine EM sampling locations and to confirm the appropriateness of planned interventions.

4.3 Unidirectional HEPA-filtered airflow is intended to minimize the risk of microbial and particulate contamination by ensuring that only first air washes over the critical zone/area. Appropriate placement of air returns, intentional placement of equipment or materials, and purposeful, slow movements supports maintenance of the classified space. In operation smoke studies provide information related to the contamination control effectiveness of the clean air system in conjunction with the operations being performed. This can be useful in optimizing operator positions and movement in respect to airflow. Conclusions from the study may ultimately require reconfiguration of the critical area, or supporting area, or both, as applicable (for example equipment or airflow devices) to resolve deficiencies that cannot be otherwise rectified.

4.4 Qualification of critical aseptic processing areas should include an airflow visualization study to assure that unidirectional airflow exists where product may be exposed and that appropriate air returns are present and operational to prevent eddies or turbulence, or both.

4.5 The approach to airflow visualization may vary depending on the lifecycle stage of the process; for example, computational fluid dynamic modeling may be appropriate during the design phase of a new aseptic zone, while a smoke study is required for existing static or dynamic airflow studies.

4.6 Airflow patterns during the study are captured by digital media device (for example, a video camera).

1.1 This guide is intended to provide best practices on how to visualize airflow in a critical area and be read in conjunction with relevant International Organization for Standardization (ISO), U.S. Food and Drug Administration (FDA), and EudraLex requirements for airflow visualization.

1.2 In this guide, the airflow visualization test (that is, smoke study) is detailed for use to understand and document airflow patterns for critical airflow environments. This test evaluates the contamination control effect of high-efficiency particulate air (HEPA)-filtered airflow, which is the basis for the contamination control effect of critical zones.

1.3 The focus of this guide is on contamination control and is not intended to evaluate airflow for operator protection when handling potential high-risk biological agents and potent, toxic, and other hazardous materials.

1.4 Areas utilizing airflow to control contamination of critical product surfaces should be evaluated visually as part of qualification.

1.4.1 Critical airflow studies are intended to verify the unidirectional nature of “first-pass air” released from HEPA filters and demonstrate its capability of minimizing the risk of contamination. Smoke studies use a visual medium (that is, tracer particles) to observe airflow patterns. The generator chosen should produce constant, neutrally buoyant, and non-toxic tracer particles/smoke.

1.5 Information from this evaluation can be used to compare the actual (physical) airflow patterns versus design and regulatory requirements, optimize airflow patterns for improved contamination control effect, evaluate operator and equipment movements impact on airflow patterns, aid in risk assessment, determine environmental monitoring sample locations, and assist in operator training. Out of scope is airflow visualization activities for investigational purposes and optimization purposes, which will have evaluation criteria associated with them.

1.6 Units—The values stated in SI units are to be regarded as the standard. No other units of measurement are included in this standard.

1.7 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.8 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.