Recent revisions to USP <797> have resulted in changes to the requirements that compounding pharmacies must adhere to, including the frequency of microbiological environmental monitoring. Below is a brief summary of the differences to expect.
USP Chapter <797> defines the minimum standards and practices to be followed for Compounded Sterile Preparations (CSPs), which apply to all personnel and locations where CSPs are prepared. While USP <797> covers several areas, including verification of compounding accuracy and sterility, responsibilities of compounding personnel, and quality assurance programs, this article’s focus is on the standards pertaining to the prevention of microbial contamination.
Previously, the requirements for air and surface sampling were based on microbial contamination risk level (low risk, medium risk, and high risk). However, in the revised edition of USP 797, Compounding Pharmacies are sorted into categories: Category 1 and Category 2. These categories are defined by the environmental controls in the compounding area and the risk of microbial contamination during the time any sterile compounded preparation is stored. Category 1 covers primary engineering controls located in a segregated compounding area which is not ISO classified. Category 2 consists of other areas previously covered by the risk-based categorization. An additional category, Category 3, has been created to define the requirements for compounding facilities assigning use dates beyond 180 days.
In addition to these organizational changes, updates to USP <797> have changed the requirements for environmental monitoring and personnel competency. These changes include stricter requirements for microbiological air and surface monitoring. Sterile compounding facilities must develop standard operating procedures for microbiological environmental monitoring, including both volumetric air and surface sampling. Beginning on November 1, 2023 , volumetric air sampling is now required at least every 6 months for Categories 1 and 2, and every month for Category 3. Surface sampling is now required every month for Categories 1 and 2, and every week for Category 3.
Further volumetric air and surface sampling is now required in response to specific events in addition to the routine sampling requirements. These specific events include the certification of new facilities or equipment, the servicing of facilities or equipment, the identification of contamination issues, the identification of concerning trends (e.g., repeatedly failing air or surface sampling), and changes in procedure that might affect the compounding environment such as a change in cleaning agent.
Compliance with these new microbiological environmental monitoring procedures requires the proper and effective handling of sampling media devices, such as contact plates. A general-purpose culture media, such as Tryptic Soy Agar (TSA) should be used for sampling.
For both air and surface sampling, careful handling is required to avoid contamination. Samples must be incubated for 48 hours at 30-35ºC and the resulting colony forming units (CFUs) are then counted to determine the total aerobic microbial burden. Samples must be incubated for an additional 5 days at 20-25ºC and then recounted in order to determine the total aerobic fungal burden. Alternatively, a second sampling device may be used and incubated concurrently to reduce total time to results. A fungal growth media like Sabouraud Dextrose (SabDex) may be used for the second sampling device.
Additionally, personnel are required to demonstrate competency in hand hygiene and garbing procedures using gloved fingerprint and thumb testing. Gloved fingertip and thumb sampling requires a sampling media device, such as an agar plate using a general-purpose culture media, like TSA. Testing is performed after the usual garbing and hand hygiene procedures but prior to the application of 70% isopropyl alcohol to gloved hands. For each person, a single agar plate is used per hand. Samples are collected by rolling the pads of the fingertips and thumb of each hand across the surface of the corresponding agar plate. Samples are incubated for 48 hours at 30-35ºC, counted, and then incubated for additional 5 days at 20-25ºC. Personnel are required to pass three initial tests. Failure of any of these tests will require the process to begin again. Routine testing must also be passed every 6 months for Categories 1 and 2, and every 3 months for Category 3.
As under previous USP <797> versions, media fill testing is required to determine competency in sterile manipulation and technique and is performed immediately following the completion of the gloved fingerprint and thumb sampling. The media fill test is performed by simulating compounding activities with Tryptic Soy Broth (TSB), a general-purpose liquid growth media. For processes where all components begin sterile, sterile TSB is used. At the end of the simulated processes, the TSB is transferred into a container matching those frequently used in the facility. For processes with non-sterile starting components, a 3% non-sterile preparation of TSB is used to simulate non-sterile-to-sterile compounding activities. In both cases, a positive control is prepared to demonstrate growth potential. Samples are incubated for 7 days at 30-35ºC and evaluated. An additional incubation period of 7 days at 20-25ºC is performed to check for additional fungal growth. Unlike the other tests, where failure of the test is determined by a threshold of counted CFUs, failure in this test is indicated by visible turbidity or other visual signs of microbial growth in the test media. Under the revised guidelines, routine media fill testing follows the same schedule as gloved fingerprint and thumb sampling, occurring every 6 months for Categories 1 and 2, and every 3 months for Category 3.
Category 1
| Air Sampling: Every 6 Months Surface Sampling: Every Month Gloved Fingertip and Thumb Sampling: Every 6 Months Media Fill Test: Every 6 Months
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Category 2
| Air Sampling: Every 6 Months Surface Sampling: Every Month Gloved Fingertip and Thumb Sampling: Every 6 Months Media Fill Test: Every 6 Months
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Category 3
| Air Sampling: Every Month Surface Sampling: Every Week Gloved Fingertip and Thumb Sampling: Every 3 Months Media Fill Test: Every 3 Months
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Though these modifications help to ensure the sterility of preparation areas, they can be burdensome due to the higher rate of required environmental surface and air sampling. More materials and personnel time are necessary in order to maintain compliance. Additionally, the documentation requirements and the implementation of new SOPs can create additional burdens.
Working with an independent, third-party laboratory like ResInnova Laboratories ensures that you maintain compliance with minimal effort. ResInnova has trained personnel competent in air and surface sampling and is well-equipped for data handling, data analysis, and SOP generation. We are ready to support you through every step of the process from sample collection through data processing. Read more about our environmental monitoring services here, or contact us for more information.
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