Which area in the pharmacy must have an air quality of ISO Class of 5 or better
USP Chapter 797 sets compounding risk levels based on the likelihood of contamination of a compounded sterile preparation (CSP).
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Knowing the level of risk corresponding to each compounded preparation is important because different rules apply to the compounding process depending on the level of risk. Proposed revisions to USP 797 are still under review and pandemic-related interim guidance is still applicable. It can be challenging to navigate which standards to follow to ensure the quality and safety of CSPs under the current conditions. Here's a quick guide comparing some of the key considerations when evaluating risk level to CSPs in your organization. As of today, USP 797 (2008) is the currently official chapter and low, medium, or high-risk levels apply. For case-by-case determination of risk level, please refer to current state waivers and federal interim guidance documents and consult the licensed healthcare professional who supervises compounding at your pharmacy. General principles of compounding risk levelIn USP 797 (2008), the risk level is defined primarily on the complexity of the compounding process. Fewer components for admixture or a lower level of product manipulation indicate low-risk conditions. Combining three or more ingredients or packages, multiple additive injections, or non-sterile ingredients indicate medium to high risk. The higher the risk level, the greater risk for contamination or lack of sterility, leading to increased risk for patient harm. USP 797 (2019, proposed) and interim guidance issued by FDA and USP in 2020 consider additional factors that may introduce risk to the final CSP. These focus primarily on the environment in which the compound is prepared. Examples include air quality, facility design, and shortage of standard personal protective equipment. All of these factors increase the risk for microbial contamination in the final CSP. While USP 797 (2019, proposed) is not currently enforceable, minding the state of control and compounding environment should guide decisions nonetheless. Refer to Table 1 for a comparative summary of current and interim BUDs, in the absence of passing a sterility test. FDA and USP Interim Guidance is indicated in bold. Note there is no interim guidance for high-risk compounding and the current USP <797> standards apply. TABLE 1Operational implications of risk level determinationDetermining risk level is important because it establishes the beyond-use date (BUD) for each CSP. The BUD is the date and time by which administration of a CSP must begin. In other words, the safe storage limit to ensure reasonable sterility of a CSP under certain conditions – without performing a sterility test. Low-risk compounding conditionsCompounding with aseptic manipulations using only sterile ingredients, products and devices in ISO Class 5 or higher air quality will generally fall in a low-risk category. Low-risk compounding includes using sterile needles and syringes to transfer sterile liquids from manufacturer-sealed ampules or vials to sterile devices or other sterile packages. It also covers manually mixing and measuring up to three manufactured products to create a CSP or nutritional solution. Examples include:
Low-risk with 12 hour or less BUD criteria* apply when a CSP is prepared under less-than-ideal circumstances, including environmental or procedural conditions, that increase the risk for microbial contamination. Examples include:
*Per USP <797> (2008), only non-hazardous and radiopharmaceutical CSPs may be prepared in an (SCA) under low-risk with 12 hour BUD conditions. However, USP <800> describes the criteria for Containment-Segregated Compounding Areas (C-SCAs) that allows for compounding of hazardous drugs with 12 hour or less BUD. Minimally, C-SCAs must have: at least 12 air changes per hour (ACPH) and maintain negative pressure of -0.01 to -0.03 i.w.c. for the room, with an externally vented containment primary engineering control (C-PEC). Medium-risk compounding conditionsIf you compound or pool multiple doses of sterile products for administration to multiple patients or to a single patient on multiple occasions and the compounding process involves more than single-volume transfer or takes a long time (such as complete dissolution or homogenous mixing), the process will usually be considered medium-risk. Generally, medium-risk CSPs do not have broad-spectrum bacteriostatic substances and are administered over multiple days. Medium-risk compounding examples include:
High-risk compounding conditionsUse of non-sterile ingredients or non-sterile devices usually creates a high-risk condition, as there is inherently greater risk of contamination from non-sterile products. Additional conditions resulting in high-risk level state include:
High-risk compounding would include making a solution that will be terminally sterilized from non-sterile bulk drug or nutrient powders or measuring or mixing sterile ingredients in a non-sterile device prior to sterilization. Ultimately, establishing risk levels for CSPs is about protecting patients from harm. The more complex the procedure, the lower state of control of the environment, or when standard operating procedures are challenged, the risk of contamination increases. When conditions are compromised, a more conservative risk level and BUD is advised. USP 797 may be on hold, but with The Joint Commission resuming inspections, it's time to reenergize programs. Learn more in our on-demand webinar, Update on recent proposed revisions to USP Chapters 795 and 797. What is ISO Class 5 PEC?To certify the PEC as an ISO Class 5 environment the certifier will perform a nonviable particle count of particles 0.5 micron or larger. To certify as ISO Class 5 the PEC will not have more than 3520 particles per cubic meter of air.
Which ISO class of clean air is most appropriate for a direct compounding area?The environment for all risk level compounding must be ISO Class 5 air quality. The most common example of this type of enclosure is a laminar air flow hood, in which air first passes through a microbial retentive HEPA filter then circulates over the critical site providing low-particulate, essentially sterile air.
How often must ISO Class 5 compounding areas be cleaned?Daily Cleaning of ISO 5 Laminar Airflow Work Bench, Biological Safety Cabinets and other PEC (Primary Engineering Controls) Minimum Cleaning Frequency: Beginning of each shift, before each batch, every 30 minutes while compounding, as spills occur, when surface contamination is suspected.
What ISO class is ante room?Under the USP 800, an anteroom is defined as “An ISO Class 7 or cleaner room” where personnel hand hygiene, garbing procedures, and other activities that generate high particulate levels are performed. The ante-room is the transition room between the unclassified area of the facility and the buffer room.
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