This article, Part 1 of 3, discusses the testing that must be performed and documented on a certification report for secondary engineering controls (SECs). Parts 2 and 3, which will be published in subsequent issues of Pharmacy Purchasing & Products, will focus on certification testing for primary engineering controls (PECs).
While engineering control certification is a requirement of USP <797>, the chapter does not specify how it must be performed and what information must be documented on a certification report. As a designated person responsible for ensuring that your cleanroom is compliant with current USP standards, it can be challenging not only to deduce from a certification report whether the appropriate testing has been performed, but also to interpret the results and determine if all aspects of testing have been properly documented. It is critical that the certification report contains the necessary information so pharmacy personnel and regulatory inspectors can verify and interpret the results to ensure the applicable requirements meet engineering control certification compliance.
The chapter references CAG-003, the Controlled Environment Testing Association (CETA) Certification Guide for Sterile Compounding Facilities, which provides guidance on certification requirements for sterile compounding facilities.1 The chapter also indicates that an equivalent may be used; however, as there is no other guide specific to the certification of sterile compounding facilities, it is strongly recommended that certification be performed in accordance with CETA’s guidelines in order to ensure adequate testing procedures are followed.
Documentation of Testing
All aspects of certification testing methods must be documented, either in an SOP that is provided with the final report, or in an explanation written in the report that details the test methods and procedures used. Without this information, it is not possible to verify that testing was performed in accordance with industry standards. Additionally, if all aspects of the data are not documented in the report, it will be challenging to determine the accuracy of the results.
An understanding of the required testing is necessary in order to determine the criteria for testing and documentation. For example, SEC certification requirements differ for a cleanroom suite versus a containment segregated compounding area (C-SCA). Notably, there are no certification requirements for a segregated compounding area (SCA) utilized for nonhazardous drugs.
Secondary Engineering Control Requirements
In a cleanroom suite with a buffer and anteroom, the following tests must be performed, and the associated data and results documented:
Airflow measurements must be taken on each HEPA filter. The airflow is measured in cubic feet per minute (CFM) using a capture hood—a large, tent-like structure that fits over the face of the filter. Results must be reported for each filter. The total CFM from the room HEPA filters must then be added together, divided by the volume of the room, and multiplied by 60 to calculate the air changes per hour (ACPH). The dimensions used to measure the room volume should be clearly identified on the certification report so that the calculations can be verified.
If the HEPA filter airflow cannot be measured using the capture hood, an alternative method must be chosen. HEPA filters that reside in areas where the large capture hood may not fit, such as over a PEC or other large piece of equipment, are the exception. In this situation, the multi-tube array or velocity meter is used to capture the velocity from multiple points on the filter. Each point is determined based on a grid pattern that reflects a representative area of the filter to be measured. All individual velocity readings must be documented on the certification report, along with the area of the filter. To calculate the CFM of the filter, the average velocity is multiplied by the area of the filter. Using a different measuring system will result in slightly different values; as such, a correction factor (kV) must be determined and applied to the final calculated value. The kV must also be documented on the report.
HEPA Filter Integrity Testing
HEPA filter integrity testing must be performed for all HEPA filters in the cleanroom suite, including any filters located in pass-throughs. This test verifies that the HEPA filters are functioning as intended and are free of leaks greater than 0.01% of the upstream aerosol concentration challenge.
In order to perform an integrity test on a HEPA filter, there must be a point of introduction upstream of the filter for the challenge medium, which is an oil-based aerosol of known particle sizes. This can be achieved by having test ports installed for each filter, by introducing the aerosol directly into a duct upstream, or through room-side challenge ports, which are an optional feature on some filter housings. The method of introduction must be documented on the report, which will serve the purpose of verifying that the filters were challenged in an appropriate location. If the test port location is not obvious, the report can also serve as a future reference for new certification technicians.
Once the aerosol is introduced, the upstream concentration must be measured. If it is not possible to physically measure the upstream concentration, it may be calculated instead. While this method is not ideal, the industry guidance from the equipment manufacturers and recommended practices allow a challenge to be calculated if the amount of aerosol introduced is below 2 Laskin nozzles.2 The method of determination (ie, calculated or measured) must be documented with the actual value.
Once the upstream aerosol concentration has been determined, the filter must then be scanned on the downstream side using an aerosol photometer. The photometer reads the percentage of the upstream concentration that has penetrated through the filter. The highest penetration percentage observed on the photometer should be reported, and not just reported as pass or ≤0.01%. Any leaks found in the filter must be documented and these areas identified on the report. Note that HEPA filters can sometimes be repaired. If the filter is repaired, the patch size and location must be documented. The size of the patch that can be applied in the field is limited to no more than 3% of the filter area and no more than 1.5” wide of the lesser dimension.
Total Particle Count Testing
Total particle count testing must be performed at each certification. The particle counts designate the room’s specific ISO classification. It is important that the particle concentration in the areas not exceed the ISO classification limits for the applicable class, which is provided in Table 1 – ISO Classes of Air Cleanliness by Particle Concentration in ISO 14644-1:2015.3
Testing must be performed under dynamic conditions, as indicated in the chapter. The requirement that particle counts be taken during dynamic conditions ensures that the SEC is maintaining the desired classification and state of control during operations. The certification report must indicate that the conditions of testing were dynamic and should provide the actual number of personnel present within the space during the testing. Each individual reading must be reported, and a diagram provided with the report that indicates where the samples were taken. The number of sample locations is based on the area of the room. ISO 14644-1:2015 details the minimum number of sample locations required based on the room area (See FIGURE 1).3 The room area must also be documented to verify that the number of locations used meets the minimum requirements for ISO classification.
In addition, note that there are a variety of particle counters on the market that have different sample volumes and measurement times, which may or may not be compliant with the requirements of ISO 14644-1:2015 to certify your space to the required ISO classification. The sample volume and sampling time must be reported. The minimum requirement is two liters and a 1-minute sample time. It is important that the instrument information is documented on the report so that the capabilities can be verified.
Room Pressure Differentials
Room pressure differentials must also be measured at each certification. The pressure requirements for each room are indicated in the associated USP chapter (ie, <797> and <800>). While the actual pressures must be verified during the certification, each facility should already have pressure-monitoring devices in place for each room where a pressure differential is required.
During the certification, the pressure differential between rooms will be measured under the door, using a manometer and tube. The results must be reported to one thousandths of an inch water column (“w.c.). Note that it is not appropriate to round the values; for example, a measurement of 0.015” w.c. rounded to 0.02” w.c. is not acceptable, as this could result in a positive pressure room not meeting the minimum pressure differential requirements. The pressure differentials must be documented for each room and the report must clearly identify the directional flow relative to the adjacent area. In addition, a smoke pattern test must be utilized to visually verify the directional airflow and document the results in the report. To ensure that the facility’s pressure monitor results are comparable with the certification results, conduct a performance verification on the facility’s monitors. Should the results vary, commence an investigation and take action to correct the variance among readings.
Containment Segregated Compounding Area Requirements
The certification requirements for a SEC that is used as a C-SCA encompass air exchange rates and room pressure differentials only. Since the area is not utilized for the full dating that a cleanroom suite provides, there are no requirements for HEPA filtration or ISO room classification. A C-SCA must have a minimum air exchange rate of 12 ACPH, calculated from the exhaust air, and maintain a differential pressure between 0.01” to 0.03” of w.c., negative to the adjacent space, per USP <800>.
In order to determine the air exchange rate from the C-SCA, the exhaust airflow must be measured from all exhaust points, totaled, divided by the room volume, and multiplied by 60 to identify the ACPH. Because we are concerned with the containment of the HDs in the C-SCA, the airflow moving out of the space and not the dilution control factor that we consider for an HD buffer room, the air exchange rate in this case would be based on the exhaust airflow. Each exhaust measurement and the total exhaust for the C-SCA must be reported. The room dimensions used to determine the room volume should be included in the report so calculations can be verified.
The certification of engineering controls is a key requirement of USP <797> and <800>, yet the chapters do not detail what information should be documented on a certification report. For SECs, airflow measurements, HEPA filter integrity testing, total particle count testing, and room pressure differentials are required. Furthermore, thorough and accurate documentation of the testing processes is necessary to demonstrate that proper testing occurred and provide regulatory inspectors with sufficient data to verify the results.
Kimberly Coughlin, BS, Director of Microbiology at Kastango Consulting Group, a TRC Healthcare Company, provides consulting on environmental monitoring, remediation, and facility design performance. She is the 2019-2021 President Elect for the Controlled Environment Testing Association (CETA) and serves as a subject matter expert for the CETA National Board of Testing (CNBT). Kimberly received NSF accreditation for the field certification of Class II Biosafety Cabinets and is accredited through the CNBT as a registered certification professional in the sterile compounding facility (RCP-SCF) discipline. Kimberly also played a lead role in the writing of ISPE’s Good Practice Guide: HVAC and Process Equipment Air Filters.
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