What’s New in Sterile Compounding?

USP develops compounding standards to help ensure quality preparations while reducing variability and risks (e.g., contamination, infection, incorrect dosing). The chart below touches on updates for sterile compounding (USP <797>), including new risk categories and assignment of beyond-use-dates, and requirements for training and competency. Keep in mind, the revision that’s effective on December 1, 2019 also requires additional facility and engineering controls, such as HEPA-filtered ceiling air, to reduce the risk of contamination with sterile compounding.2,3 For more details, get our CE course, Sterile Compounding: Quality Standards and Requirements. And share our technician tutorials with your techs, Sterile Compounding: Keeping It Clean and Drug Expiration and Beyond-Use Dates, to get technicians up to speed on the latest in sterile compounding.

Abbreviations: BUD = beyond-use date; CSP = compounded sterile preparation; USP = United States Pharmacopeia.

Question

Pertinent Information

What are the differences between USP <795>, <797>, and <800>?

USP <795>: pharmaceutical compounding of NON-sterile preparations.

USP <797>: pharmaceutical compounding of sterile preparations.

USP <800>: handling of hazardous drugs in the healthcare setting.

If compounding a preparation that includes a hazardous drug, both applicable chapters should be followed. For example:

  • Follow USP <795> and <800> when compounding a NON-sterile prep containing a hazardous drug.
  • Follow USP <797> and <800> when compounding a sterile prep containing a hazardous drug.

What is the definition of sterile compounding?

Sterile compounding is defined as combining, admixing, diluting, pooling, reconstituting, repackaging, or otherwise altering a drug or bulk drug substance to create a sterile medication.1

For what will the “designated person” be responsible?

A person or persons must be designated by a hospital as responsible and accountable for the performance and operation of the facility and personnel in the preparation of CSPs.1 They must oversee compliance, including training and competency, and their documentation.1-3

What are training and competency requirements for sterile compounding?

Training and competency requirements for sterile compounding are now more stringent.

  • Initial training, including demonstration of core skills (e.g., aseptic technique, calculations, cleaning and disinfection, hand hygiene, use of equipment), fingertip testing, and media-fill testing, will continue to be required.1,2
  • Demo of hand hygiene, garbing, and aseptic technique plus media-fill test followed by fingertip testing will be required every six months, for all compounding personnel, and core skill testing will be required annually.3

What are the space requirements for sterile compounding?

Sterile compounding must take place in a clean room suite or a segregated compounding area.1

  • A clean room suite includes an ante room and a buffer room housing a laminar airflow system (e.g., hood) or a restricted-access barrier system (e.g., glove box). Or, a pharmaceutical isolator can be placed in a buffer room, without an ante room. These areas must achieve and maintain specified air quality.1
  • A segregated compounding area is a location outside of a clean room suite, with a laminar airflow system, restricted-access barrier system, or a pharmaceutical isolator that meets certain specifications. For example, the area should not be close to unsealed windows, doors that connect to the outdoors, or high-traffic areas. A segregated compounding area must have a visible perimeter.1

How will compounded sterile preparations be classified?

Low-, medium-, and high-risk categories will be replaced with Category 1 and Category 2.1

  • Category 1 applies to CSPs prepared in a segregated compounding area.3
  • Category 2 applies to CSPs prepared in a clean room suite.3

There is still an allowance for immediate-use CSPs (i.e., prepared outside of a sterile environment). Recall that immediate-use applies to CSPs mixed from no more than three different sterile products and intended for direct and immediate administration to a patient.1 Keep in mind that multiple containers of the same med count as one product. For example, if you prep a norepinephrine drip using a bag of normal saline and four ampules of norepinephrine, you’re only using two different sterile products.2

What are the maximum beyond-use dates for compounded sterile preparations?

Maximum beyond-use dates:

  • Category 1 CSPs: 12 hours at room temp and 24 hours refrigerated.1
  • Category 2 CSPs made from sterile components: 4 days at room temp, 10 days refrigerated, and 45 days frozen.1
  • Category 2 CSPs made with one or more non-sterile components: 1 day at room temp, 4 days refrigerated, and 45 days frozen.1
    • Note that beyond-use dates for Category 2 CSPs may be longer if they are tested for sterility (and pass) or terminally sterilized.1

These beyond-use dates are in contrast to those that could be assigned prior to the revision. For example, low-risk CSPs had a maximum beyond-use date of 48 hours at room temp.

For an immediate-use CSP, administration must be started within 4 hours from the start of prep.1 This is in contrast to the previous version, where administration of immediate-use CSPs had to be started within one hour.

With regard to proprietary bag and vial systems, docking and activation for immediate administration to an individual patient is not considered compounding. But docking and storing for future activation is considered compounding, and the beyond-use date must be no longer than what’s specified by the manufacturer.1

If a component of a CSP has an expiration date shorter than a CSP’s maximum BUD, or stability that’s less than the CSP’s maximum BUD, the shorter BUD or expiration date will need to be assigned as the CSP’s BUD.1

What is the maximum beyond-use date for a single-dose vial?

A single-dose vial that’s punctured in at least an ISO Class 5 environment may be used for up to 12 hours as long as storage requirements, such as refrigeration, are met. This is in contrast to the previous version, where this BUD was only six hours.1

What are the new requirements for air and surface sampling?

The frequency of surface sampling has been changed from “periodically” to monthly.2 The frequency of air sampling remains every 6 months.3

Where must a sink for hand hygiene be located?

The sink may be located inside the ante room, or outside the ante room. However, if hazardous drugs are compounded in a clean room suite, the sink must be located inside the ante room.2

What are requirements with regard to cosmetics, jewelry, etc?

Cosmetics must be removed, as well as hand, wrist, and exposed jewelry, and earbuds or headphones.1 This includes wedding rings.2 Plus, eyeglasses must be cleaned.1

Hospitals are responsible for determining how to cover jewelry that cannot be removed, such as dermal piercing.1,2

What changes are being made to requirements for garbing?

The same garb is required regardless of whether a Category 1 or Category 2 CSP is being compounded.2

Individual hospitals must specify order of garbing, since it will depend on the type of garb required and where the sink for hand hygiene is placed, such as inside or outside the ante room.1 However, it is recommended that donning and doffing garb not take place at the same time and in the same place, to help reduce the risk of contamination.1

What will need to be considered with regard to cleaning compounding areas?

The addition of a sporicidal agent to cleaning and disinfecting regimens is now required at least monthly for clean room surfaces.2 One option is to use an EPA-registered one-step disinfectant cleaner, with sporicidal activity.1,2 Note that isopropyl alcohol is not a one-step disinfectant cleaner.2

What documentation is needed for compounded sterile preparations?

A Master Formulation Record is required for CSPs prepared for more than one patient and for CSPs prepared from non-sterile ingredients. This “recipe” must include information such as the name, strength, and dosage form; the identities and amounts of all ingredients; complete instructions for preparation; the beyond-use date; and the type and size of container that must be used.1

A Compounding Record must be created for each CSP made to document the compounding or repackaging process.1

  • A Compounding Record must include specific information such as name, strength, and dosage form; date and time of prep; individuals involved in prep of the compound; and lot numbers and expiration dates of ingredients.1
  • Check your pharmacy policy to find out what will be used as a Compounding Record in your facility. For example, an order or label may be used, or these may be stored electronically.1

Keep the Master Formulation Record, the Compounding Record, and results of any required release testing readily retrievable for at least three years after preparation of a CSP, or longer, if required by state laws or regulations.1

When and how will USP <797> be enforced?

The revised USP <797> will go into effect on December 1, 2019.1,2

Ensuring compliance with USP <797> is the responsibility of regulators (e.g., FDA, state board of pharmacy). Regulatory bodies may have a different official date for enforcement. USP is not responsible for enforcing USP <797>.2 Get our CE, Compounding: Sterile Compounding and USP Chapter <797>, to find more info about what is happening in your state.

Project Leader in preparation of this clinical resource (350818): Stacy A. Hester, R.Ph., BCPS, Associate Editor

References

  1. United States Pharmacopeia. USP general chapter <797> pharmaceutical compounding – sterile preparations. 2019. https://www.usp.org/compounding/general-chapter-797. (Accessed July 16, 2019).
  2. United States Pharmacopeia. FAQs: <797> pharmaceutical compounding – sterile preparations. https://www.usp.org/frequently-asked-questions/pharmaceutical-compounding-sterile-preparations. (Accessed July 16, 2019).
  3. Premier. 2019 USP <797> preparation checklist. https://www.premierinc.com/downloads/Premier-2019-USP-797-Preparation-Checklist.pdf. (Accessed July 16, 2019).

Cite this document as follows: Clinical Resource, What’s New in Sterile Compounding? Pharmacist’s Letter/Prescriber’s Letter. August 2019.

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