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Unplanned Cleanroom Power Outage Time Limit and Recovery Determinations for Aseptic Processing Areas

Introduction How can the time between a cleanroom power outage and loss of environmental control in the critical area be determined? Once the power is restored, how can the time it takes to recover the desired environmental conditions be determined? An interruption of power supply to the HVAC systems may produce a “loss of control” which can be defined as a breech in the integrity of the controlled areas in sterile manufacturing. Appropriate steps to be taken during and after an interruption of air supply to the aseptic processing area (APA). (These steps should be placed into site procedures before the studies recommended in this document are executed.) Qualification studies should be carried out to define a time limit after which the controlled environment reaches or exceeds action levels for particulates, temperature, humidity, and pressure differential. To assist in meeting these requirements, this guidance will provide recommendations: • To assist in the qualification of an “in control” time period after power loss to

a controlled environment. • To assist in the qualification of a time period for full recovery of the controlled

environment following power restoration. It should be noted that this guidance is intended for Aseptic Processing Areas which are defined as those controlled environments consisting of Grade A or Grade B classifications. The recommendations of this document can be applied to other classifications (e.g., Grade C) depending upon a risk analysis by the site. In addition, this guidance is primarily concerned with pressure drops in a controlled environment due to a power outage to the central HVAC system. A Power failure occurrence in an individual air handling unit is beyond the scope of this document. Recommendations & Rationale for Recommendations

Title: Unplanned Cleanroom Power Outage Time Limit and Recovery Determinations for Aseptic Processing Areas

Guidance Number: 118 Prepared by: Date: Supersedes:

Checked by: Date: Date Issued:

Approved by: Date: Review Date:

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interruption. For example, the power interruption study should take into account the potential maximum number of personnel that may be present in the APA and what actions the personnel would perform during the interruption, such as exiting the APA or reducing all movements to nominal tasks. o Air Quality Non-viable particulate and viable microbiological air tests used to determine a power interruption time limit are quite similar to the qualification studies used to classify the area. The monitors are placed in the controlled area while the air handling system is operational. At time zero, power to the air handling system is shut down and the air is continuously monitored for a defined length of time. For non-viable particulate monitoring, the number of locations can be determined by taking the square root of the total controlled surface area. It is also prudent to place additional particulate monitors at critical locations based on a risk analysis. The number and placement of passive and/or active viable microbiological monitors can be determined by risk analysis. The risk analysis placement should include locations that have a high potential for microbial presence based upon areas that are difficult to clean, historical data, production activities, previous qualification data, traffic patterns, and line configurations. Uniform coverage of the controlled area may also be utilized by the inclusion of additional monitoring points to ensure that the viable particulate profile is accurately represented throughout the area. Acceptance criteria for air quality tests should be no higher than the action levels employed during routine production. o Pressure differentials and smoke studies Another key parameter in defining a power interruption time limit is the flow of air through the classified area. Pressure differentials are ideal for this purpose since data can be monitored continuously and can give an indication of the potential change in the flow of particulates from adjacent areas. As in air quality tests discussed above, pressure differentials are monitored after the air handling system is shut down and the time measured until the differential reaches a predetermined acceptance criterion. However, unlike the air quality test, the routine production action levels may not be appropriate, especially in controlled environments with openings (e.g. mouseholes). The minimum acceptance criterion should be pressure equilibrium between the test area and an adjacent controlled area of lower classification (i.e. no reversal of air flow). As with air quality testing, a safety margin should be built into the acceptance criteria (i.e. requiring slight positive pressure in room being tested). For example, if non-viable particulates levels reach the action limits for the room at a pressure differential of 2 Pascals, then the acceptance criteria should have a minimum pressure differential greater than 2 Pascals.