USP Chapter 797 sets compounding risk levels based on the likelihood of contaminating a compounded sterile preparation (CSP) with microorganisms, spores, endotoxins or other foreign material. 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.
Here's a quick guide to the types of situations that fall under each level of risk—low, medium or high—according to USP 797.1 For case-by-case determination of risk level, please consult the licensed healthcare professional who supervises compounding at your pharmacy.
Compounding 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. Without performing a sterility test, CSPs should not be stored longer than 48 hours at a controlled room temperature, 14 days in refrigerated settings or 45 days if frozen solid at -20 degrees Fahrenheit or colder.
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.
If 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. Without passing a sterility test, medium-risk CSPs may be stored for 30 hours at room temperatures of 25 to 40 degrees Fahrenheit, 9 days at cold temperatures and 45 days if frozen solid and held at -20 degrees or less.
Medium-risk compounding examples include compounded total parenteral nutrition fluids that require multiple injections, detachments and attachments of nutritional products to a device that delivers all the nutritional components to the final sterile container as well as filling injection or infusion devices with multiple sterile drug products and evacuation of air from the device reservoirs before filling.
Use of non-sterile ingredients or non-sterile devices usually creates a high-risk condition. Exposing sterile ingredients and devices to air quality below ISO Class 5 will create a high-risk compounding situation, as will the prolonged storage of opened or partially-used products that lack antimicrobial preservatives in an environment in less than ISO Class 5 conditions. In addition, assuming rather than verifying directly or by examining the labeling and documentation that the chemical purity and strength of bulk ingredients meet their specifications establishes a high-risk condition. In the absence of passing a sterility test, high risk compounded sterile products cannot be stored for more than 24 hours at controlled room temperature, more than three days in cold temperatures or for more than 45 days if frozen solid and held at -20 degrees Fahrenheit or less. Special care must be taken in high-risk compounding. Please refer to Chapter 797 for more details.
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.
- <797>ASHP Guidelines on Compounding Sterile Preparations (2014).