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Cleanroom Certification Under USP <800>

October 2020 : Cleanrooms & Compounding - Vol.17 No. 10 - Page #8

Pharmacy Purchasing & Products recently held a webinar entitled
USP Compliance: Preparing for Cleanroom Certification,
presented by Jim Wagner.

The following questions were submitted by attendees.
The webinar slides and full presentation can be downloaded at


Q: When is a smoke test required for the cleanroom suite, and not just the PEC?

A: A room smoke study is not necessary for most ISO Class 7 or 8 cleanrooms. According to USP Chapter <797>, a room-wide smoke pattern test is only required in cleanrooms with ceiling-mounted returns or exhaust grilles in order to verify there is no stagnant air in that room. Following the room-wide smoke test, a three-time cleaning should be conducted. Additionally, for facilities experiencing unidentifiable environmental monitoring problems, a smoke study can be valuable as a diagnostic tool.

Q: Should an ISO 7 room be shut down immediately if the HEPA filter leak testing fails during certification?

A: A leak in a HEPA filter that is just over the allowable limit may not have any substantial effect on the room; nevertheless, if it is out of spec, it is out of tolerance. Fortunately, leaking HEPA filters usually can be patched by the certifier. The certification guide referenced by USP allows a patch of up to 3% of the effective area of the filter, but no more than 1.5 inches wide. Once the patch is in place and the certifier ensures the filter is leak free, the facility can be used without issue. If the filter was not able to be adequately sealed, at a minimum, enhanced environmental monitoring would be necessary until the replacement filter is installed. If the certifier is not able to ensure the filter is leak free, or if the leak is too substantial for a patch, then it would be prudent to consider the room served by that filter to be a Segregated Compounding Area (SCA) and to limit BUD to 12 hours at room temperature until a replacement filter can be installed and certified as leak free.

Q: When designing an ISO 7 buffer room with a minimum air change per hour (ACPH) requirement of 30, would you recommend increasing the actual ACPH to 45 to 60 so that it consistently performs above 30 over time?

A: Establishing total ACPH is room-dependent. For a nonhazardous (positive pressure) buffer room, 30 ACPH is acceptable from the HVAC as long as the HEPA filtered air from the hoods extends the ACPH beyond 60, which it typically does. While it is common to certify these rooms to 30 or 35 ACPH from the HVAC, the total ACPH is typically closer to 100 due to the HEPA-filtered air from the hood(s). The 2019 version of USP <797> says “The ACPH from HVAC, ACPH contributed from the PEC, and the total ACPH must be documented on the certification report.”1

Conversely, in the negative-pressure chemo room, the PECs must be vented to the outside; therefore, there is no additional gain of HEPA-filtered air so the HVAC air change rate will be the same as the total air change rate. It is also likely there is a refrigerator in the room. Therefore, the room should be designed to have a minimum of 50 to 60 ACPH. This underscores the importance of certifying a room to its design, rather than to the USP minimum. If a room is designed for 50 ACPH but is only achieving 30 ACPH, quite simply, that room is not working as designed, so it should not pass certification.

In the anteroom, there is no re-circulated HEPA filtered air from a room source because there typically are no PECs in this room. The HVAC and total air change rate will again be the same. The anteroom typically houses a water source as well as ungowned staff. Therefore, the anteroom should be designed to achieve 50 to 60 ACPH. In all cases, if the room is designed for a higher air change rate, that should be the acceptance criteria for that room, not the USP minimum.

Q: Does every positive growth result require additional testing?

A: Any positive growth should be addressed based on your established alert and action levels. It is possible to have growth and continue operations, as long as the growth remains under your action levels. Should alert levels be reached, additional attention must be paid to monitor for any developing trends.

Q: Is it possible for an anteroom to also serve as a segregated compounding area?

A: This is technically acceptable. In some facilities, the anteroom includes a hood for STAT preps; the reasoning being that staff can then avoid entering the positive pressure buffer room. However, this is no longer a practical solution, as any compounding in the anteroom now requires full garb; once a staff member is fully garbed, they might as well compound in the buffer room.

Q: Should the pharmacy maintain a dedicated ladder for the cleanroom?

A: A dedicated ladder is a good idea. The certifier will need to access the top of the biological safety cabinet, as well as reach the ceiling for the HEPA filters, so a simple stepstool does not suffice. I recommend at a minimum a four-foot stepladder that accommodates up to 300 pounds; a six-foot ladder is even better.

Q: For an HD compounding room, is it important to establish a maximum negative pressure?

A: It is important to recognize that a room can be too negative. In the 2008 version of USP <797>, a minimum of 0.01” w.c. was established, but the maximum negative pressure was not addressed. The result of rooms operating at pressures higher than 0.030” w.c. negative typically manifested in failed environmental monitoring tests. Recognizing the problems associated with negative pressure rooms whose vacuum exceeds .030” w.c. to the adjacent space, USP <800> resolved this by establishing a range of negative pressure between 0.010 and 0.030” w.c. While the current version of USP <797> has been remanded back to the Expert Committee, USP <800> is final. Hence, the direction in USP <800> should be followed.


  1. USP General Chapter <797>. Pharmaceutical Compounding – Sterile Preparations. Second Supplement to United States Pharmacopeia and National Formulary (USP 42-NF37). June 3, 2019. Accessed September 10, 2020.

James T. Wagner is principal of Controlled Environment Consulting and has over 30 years’ experience evaluating facilities and primary engineering controls used for aseptic processing.


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