Understanding CAI and CACI Certification Reports

September 2021 - Vol.18 No. 9 - Page #14
Category: CAIs/CACIs (Compounding Aseptic Isolators & Compounding Aseptic Containment Isolators)

This article, Part 3 of 3 in our series on Understanding Certification Report Requirements, examines the testing that must be performed and documented for CAIs and CACIs. Part 1 discussed Certification Report Requirements for SECs and was published in our January issue. Part 2, focused on Certification Testing for LAFWs and BSCs, was published in our April issue.

Engineering control certification is a key requirement of USP <797> and <800>, yet the chapters do not specify how it must be performed and what information must be documented on a certification report. For the designated person responsible for ensuring that the 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.

Compounding Aseptic Isolators

Compounding aseptic isolators (CAIs) are used for non-hazardous sterile compounding and serve the same purpose as laminar airflow workstations (LAFWs) in providing product protection. However, because the construction of CAIs is somewhat more complex than LAFWs, additional tests are required to ensure proper operation. The testing requirements are provided in CETA’s Application Guide CAG-002-2006, CETA Compounding Isolator Testing Guide.

Airflow Velocities

Airflow velocities are measured in the main chamber and in most cases in the pass-through chamber of the unit. Readings must be taken on the grid pattern that is specified by the manufacturer and the average must fall within the manufacturer-determined velocity range. Any uniformity requirements for the individual reading will also be provided by the manufacturer, as applicable. All readings must be documented accordingly on the report.

HEPA Filter Integrity Testing

HEPA filter integrity testing must be performed on the supply filter(s). The site of aerosol introduction is before the motor blower that delivers the air to the unit. The upstream concentration can be measured through a manufacturer-supplied measurement port or calculated; the results must be documented along with the downstream penetration percentage. In addition to recording the final result, the average velocity used to calculate the cubic feet per meter (CFM) to determine the calculated challenge (or the actual measured challenge) must be recorded. Likewise, any repairs that occur must be reported.

Chamber Pressure Tests

Chamber pressure tests are required to determine if the unit can maintain positive pressure during operation. The pressure of the unit is critical, as it provides a barrier to the adjacent space. A series of tests are performed simulating hand insertion and removal. The pass-through doors are also manipulated during this test. As these simulations occur, the pressure is recorded and must demonstrate that the unit does not change from positive to negative during any of these manipulations. The results must be documented for each test.

Site Installation Assessment Tests

Site installation assessment tests are required for those CAIs in which the manufacturer includes an alarm for the chamber pressures. In this case, the alarm must be tested and verified to be within the manufacturer-provided specifications. Note that not all CAIs have this alarm.

Airflow Smoke Pattern Test

An airflow smoke pattern test must be performed at each certification. Do not confuse this test with the dynamic airflow smoke pattern testing, as this is not a dynamic test. During this test, the visual smoke source is passed along the work area and over extruding features installed within the CAI, such as the gloves, gauntlets, and IV bars. It is critical that the direct compounding area (DCA) is clearly identified during the study. While most CAIs will demonstrate some areas of turbulent airflow, the airflow to the DCA must be free of any areas of refluxing or dead spots. The smoke must also be removed through the returns without reentry. While this is a pass/fail test, the results of the smoke observation must be documented on the report. A passing result would report smooth downflow with a minimum of dead spots or reflux (upward flow) at the obstructions and across the critical work zone and is removed to the returns without reentry.

Preparation Ingress and Egress Test

A preparation ingress and egress test must occur at each certification. The purpose of this test is to ensure that the CAI can maintain ISO Class 5 conditions during the material transfer process. This test is performed by taking a particle count in the unit to verify that ISO Class 5 conditions are achieved. Once the particle count is verified, the materials are transferred into the pass-through chamber. At the conclusion of the manufacturer’s listed purge time, the materials are then transferred into the main chamber of the unit while the particle counter is running. The particle counts must be recorded during the process and for a period of 1 minute thereafter. All results must be documented along with a confirmation that the background counts meet or exceed 3,520,000 particles per cubic meter and that the main chamber of the unit maintains ISO Class 5 conditions during the transfer. If the manufacturer has not provided a purge time, work with your certifier to determine an appropriate purge time for the unit.

Total Particle Count Testing

Total particle count testing must occur in the CAI under dynamic conditions or with simulated compounding activities that are representative of the actual compounding activities. As such, the dynamic conditions must be conducted by pharmacy personnel, not the certification technician. The CAI must be certified to meet ISO Class 5 particle count concentration levels no greater than 3,520 particles per cubic meter. The report must indicate that the sampling conditions were dynamic and include a diagram of the sampling locations as well as document each individual count reported as particles per cubic meter. The sample volume and sample time must also be reported.

Compounding Aseptic Containment Isolators

Compounding aseptic containment isolators (CACIs) are used for hazardous sterile compounding and their testing requirements are provided in CETA’s Application Guide, CAG-002-2006, CETA Compounding Isolator Testing Guide.

Airflow Velocities

Airflow velocities are measured in the main chamber and in most cases in the pass-through chamber of the unit. Readings must be taken on the grid pattern that is specified by the manufacturer and the average must fall within the manufacturer-determined velocity range. Any uniformity requirements for the individual reading will also be provided by the manufacturer, as applicable. All readings must be documented accordingly in the report.

HEPA Filter Integrity Testing

HEPA filter integrity testing must be performed on both the supply and exhaust filters. The method of aerosol introduction depends on the type of unit and whether it is recirculating or a total exhaust CACI. In a recirculating unit, the aerosol may be introduced at the work surface where it will then recirculate through the unit and allow the supply and exhaust filters to be challenged. In the case of a total exhaust unit that does not recirculate, the aerosol would need to be introduced individually to the supply filter and then to the exhaust filter. Since the CACI is used for HD compounding, the upstream concentration must be calculated to avoid exposure to potentially contaminated air within the unit. The documentation must include the calculated upstream concentration, the downstream penetration percentage, and the average velocity used to calculate the CFM to determine the calculated challenge. In addition, any repairs that occur must be recorded.

Chamber Pressure Tests

Chamber pressure tests are necessary to determine whether the unit can maintain negative pressure during operation. The pressure of the unit in this case is critical, as it provides a barrier to the adjacent space. A series of tests are performed simulating hand insertion and removal. The pass-through doors are also manipulated during this test. As these simulations occur, the pressure is recorded and must demonstrate that the unit does not change from negative to positive during any of these manipulations; this information must be documented for each test.

Site Installation Assessment Tests

Site installation assessment tests serve to ensure that the exhaust connection, alarm functions, and door interlock of the CACI are functional. The tests and criteria will vary depending on the manufacturer of the unit. Some CACIs have a hard exhaust transition connection, while others have a canopy connection. The certification report must include the results of these tests and indicate whether they meet the manufacturer’s acceptance criteria.

Airflow Smoke Pattern Test

An airflow smoke pattern test must be performed at each certification. Again, this test is not to be mistaken for the dynamic airflow smoke pattern testing, as this is not a dynamic test. During this test, the visual smoke source is passed along the work area and over extruding features installed within the CACI, such as the gloves, gauntlets, and IV bars. It is critical that the DCA is clearly identified during the smoke studies. While most CACIs will demonstrate some areas of turbulent airflow, the airflow to the DCA must not display any areas of refluxing or dead spots. The smoke must also be removed through the returns without reentry. The results of this test must be documented on the report.

Preparation Ingress and Egress Test

A preparation ingress and egress test must occur at each certification. The purpose of this test is to ensure that the CACI can maintain ISO Class 5 conditions during the material transfer process. This test is performed by taking a particle count in the unit to verify that ISO Class 5 conditions are met. Once the particle count is verified, the materials are transferred into the pass-through chamber. At the conclusion of the manufacturer’s listed purge time, the materials are then transferred into the main chamber of the unit while the particle counter is running. The particle counts must be recorded during the process and for a period of 1 minute thereafter. All results must be documented along with a confirmation that the background counts met or exceeded 3,520,000 particles per cubic meter and that the main chamber of the unit maintains ISO Class 5 conditions during the transfer. If the manufacturer has not provided a purge time, work with your certifier to determine an appropriate purge time for the unit.

Total Particle Count Testing

Total particle count testing must be taken in the CACI under dynamic compounding conditions or with simulated compounding activities that are representative of the actual activities. The dynamic conditions must be conducted by pharmacy personnel, not the certification technician. The CACI must be certified to meet ISO Class 5 particle count concentration levels no greater than 3,520 particles per cubic meter. The report must indicate that the sampling conditions were dynamic and include a diagram of the sampling locations as well as document each individual count reported as particles per cubic meter. The sample volume and sample time also must be reported.

Particle Containment Integrity and Enclosure Leak Test

A particle containment integrity and enclosure leak test is performed specifically for CACIs to determine if there is any potential particle contamination from unsealed construction joints, seams, glove ports, and entry/exit points to the main chamber. Particle concentrations are elevated on the exterior of the unit and must be verified to be at least 3,520,000 particles per cubic meter. The interior of the unit is then scanned with a particle counter along all construction joints, seams, access panels, seals, gaskets, and glove ports. Any detected leaks cannot exceed ISO Class 5 particle concentration levels (3,520 particles per cubic meter). The results of the test must be documented in the report.

Additional Documentation Requirements

Equipment calibration requirements will vary depending on the instruments used and the manufacturers’ recommended procedures. Nonetheless, it is critical to require calibration certificates be included with the final report for each piece of certification equipment that requires calibration. This ensures that the equipment used to perform testing is operating within its tolerated calibration interval. Ultimately, this documentation provides the evidence needed to establish the credibility of the report’s findings.

Conclusion

The first step to ensuring your facility is appropriately certified is to work with your certifier to ensure there are no missing elements during an inspection. To gain a deeper understanding of the certification and associated documentation requirements, CETA’s application guide, CAG-008, Certification Matrix for Sterile Compounding Facilities, is an excellent resource for clarifying what should be documented on the certification report for secondary engineering controls. Further information is available in CETA’s application guide, CAG-003, Certification Guide for Sterile Compounding Facilities, and CETA’s CAG-002-2006, Compounding Isolator Testing Guide.

Because the format of certification reports varies among the different certifier companies, it is important to understand the data that must be documented so that all aspects of the certification can be verified and results confirmed to be compliant with the USP requirements. In addition, the certification report will be viewed by accreditation auditors and regulatory inspectors, so it is critical that the information provided be thorough, accurate, and verifiable.


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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