Government Relations

Frequently Asked Questions (FAQs) about USP <797>

Specific Questions about USP <797> – Equipment & Areas

Specific Questions about USP <797> – Equipment

Would a facility be in compliance with USP <797> if a "turbulent airflow" compounding aseptic isolator (CAI) is employed to compound or dispense sterile drug preparations (assuming that the placement of the above CAI and personnel cleansing meet the requirements as stated in USP <797>)?
Although the USP <797> contains the statement: "The use of technologies, techniques, materials, and procedures other than those described in this chapter is not prohibited so long as they have been proven to be equivalent or superior with statistical significance to those described herein," it appears that compounding aseptic isolators generally do not meet the following requirements stated in USP <797> [emphasis added]:

  • "Direct Compounding Area (DCA)—A critical area within the ISO Class 5…primary engineering control (PEC) where critical sites are exposed to unidirectional HEPA-filtered air, also known as first air."
  • "First Air—The air exiting the HEPA filter in a unidirectional air stream that is essentially particle free."
  • "Segregated Compounding Area—A designated space, either a demarcated area or room, that is restricted to preparing low-risk level CSPs with 12-hour or less BUD. Such area shall contain a device that provides unidirectional airflow of ISO Class 5 ... air quality for preparation of CSPs and shall be void of activities and materials that are extraneous to sterile compounding."
  • "The airflow in the PEC [primary engineering control] shall be unidirectional (laminar flow),..."

Also, although turbulent air flow can be acceptable within 'closed' isolators, compounding aseptic isolators are generally considered 'open' isolators. One of the key points when determining if an isolator is closed or open is whether or not particles are allowed to pass unfiltered from the room to the isolator during material transfer. Most turbulent flow isolators especially when combined with a static pass-through (the so-called 'open' isolators) have the possibility that contamination might be brought into the isolator when the materials are transferred in and out through an interchange chamber. Hence, 'turbulent airflow' isolator (either CAI or compounding aseptic containment isolator [CACI]) generally does not meet the requirements in USP <797>.

Can the same hood be used to compound low-risk and medium-risk levels radiopharmaceuticals?
Yes, if the low-risk-level radiopharmaceutical and the medium-risk-level radiopharmaceutical are not prepared in the same hood simultaneously and the hood is not located in a segregated compounding area (i.e., the hood must be located in an ISO Class 7 or cleaner air environment).

More information

Can a refrigerator be kept in the buffer area to store reagent kits that need to be refrigerated?
Dust-generating items, such as the condenser coils and cooling fan behind a refrigerator's kick plate or toe grill, should be avoided in the buffer area.

More information

Do fume hoods or dispensing hoods comply with USP <797> requirements?
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.

A fume hood, often referred to as a chemical fume hood, is typically a vapor containment and exhaust hood. Fume hoods are used in nuclear medicine labs to store and handle radioactive gases (e.g., Xe-133), volatile radioisotopes (e.g., I-131 sodium iodide solution), and hazardous chemicals (e.g., chromatography solvents such as acetone or methyl ethyl ketone). Fume hoods are NOT suitable for sterile compounding activities.

A dispensing hood, as traditionally marketed to nuclear medicine facilities, is typically a lead-lined enclosure with a leaded glass view panel. Although quite effective at providing radiation protection, this type of hood typically does not incorporate HEPA filtered air and does not achieve ISO Class 5 air quality. Hence, traditional dispensing hoods are NOT suitable for sterile compounding activities.

(Added September 18, 2008)

Does the current rule now require that the area(s) surrounding the isolation unit be ISO Class 7 rather than ISO Class 8?
For compounding Low-Risk CSPs with 12-Hour or Less BUD, the ISO Class 5 unit can be located in a segregated compounding area.

For compounding Low-Risk Radiopharmaceutical CSPs, the ISO Class 5 unit must be located in an ISO Class 8 (or better quality) environment.

For compounding Low-Risk [non-radiopharmaceutical] CSPs, the ISO Class 5 unit must be located in an ISO Class 7 environment.

For compounding Medium- or High-Risk Radiopharmaceutical CSPs, the ISO Class 5 unit must be located in an ISO Class 7 environment.

In addition to the air-quality classification mentioned above, USP <797> states: "These radiopharmaceuticals shall be compounded using appropriately shielded vials and syringes in a properly functioning and certified ISO Class 5 PEC located in an ISO Class 8 or cleaner air environment to permit compliance with special handling, shielding, and negative air flow requirements."

What is allowed in the room surrounding the isolation unit? Does the isolation unit have to be in a room completely separate from all other radiopharmacy functions?
The area surrounding the ISO Class 5 unit (either the buffer area or the segregated compounding area) should be separated from activities not essential to the preparation of CSPs. Placement of devices (e.g., computers, printers) and objects (e.g., carts, cabinets) that are not essential to compounding should be restricted or limited, depending on their effect on air quality in the compounding environment.

Does USP <797> not allow for sinks or drains to be in hot labs? If that is the case, does that mean that you are no longer allowed to have an emergency eye wash sprayer, or any other type of emergency decontamination in that area?
According to USP <797>, the buffer area (or clean room) shall not contain sources of water (sinks) or floor drains. Sinks or drains should not be located adjacent to the ISO Class 5 primary engineering control (e.g., laminar airflow hoods). An emergency eyewash or shower can be installed in an ante-area/room or a portable emergency eyewash station can be kept in the buffer area/clean room (the cleaning and disinfecting of this station should be performed per USP <797> requirements).

Has anyone attempted to add their regular Pharmacy Department to their existing Radioactive Materials License to include a sterile compounding area?
We are not aware of any nuclear medicine lab that has amended their Radioactive Materials License to include a sterile compounding area within the regular Pharmacy Department in order to comply with USP <797>. Certainly there are some facilities where the radiopharmacy lab is part of, and is operated by, the Pharmacy Department, but such examples are uncommon and were established for a variety of reasons other than solely because of USP <797>. Barriers to this idea may include, but are not limited to:

  1. Radioactive materials regulations or license conditions that specify negative pressure in areas where radioactive materials are prepared and stored in contrast to positive pressure in areas where sterile drugs are prepared.
  2. Possible requirement for additional radiation shielding in walls, etc.
  3. Concern about radioactive contamination control.
  4. If pharmacy facilities are used for radiopharmaceuticals, the pharmacy may be required to obtain additional State Board of Pharmacy licensing as a nuclear pharmacy, which then may require that all radiopharmaceuticals be prepared and dispensed by, or under the supervision of, a qualified nuclear pharmacist.

More information

I understand tagging blood has to be in a segregated area. If that is correct, can bulk kits be made in the same area just at different times when blood products are not present? OR does that segregated area have to be exclusively for blood tagging (RBCs)?

USP <797> requires that handling of biological material (e.g. patient blood) shall be clearly separated from routine handling procedures and equipment. Although an exclusive area for blood labeling would be desirable, use of the same area for other activities at different times could be allowed following thorough cleaning and disinfecting to avoid cross-contaminations.

Furthermore, as long as the following requirements are met, the same area can be used for tagging blood and reconstituting bulk kits:

When compounding activities require the manipulation of a patient’s blood-derived or other biological material (e.g., radio labeling a patient’s or donor’s white blood cells), the manipulations shall be clearly separated from routine material-handling procedures and equipment used in CSP preparation activities, and they shall be controlled by specific SOPs in order to avoid any cross-contamination.

I have built a box from one-inch thick Plexiglas to draw Y-90 SIRSphere doses. I do not wish to give up the protection from the box to comply with USP <797>. This box protects me from the radiation as well as serves as a containment area in case of a splatter or spill. The dimensions of the box are approximately 1x1.5x2 feet. How do I comply with <797> with this process? I have to puncture a vial a minimum of two times and sometimes three or four depending on what the physician has ordered. It is administered within one hour of drawing it up.

Up to two needle punctures and administration within one hour would allow Y-90 SIRSpheres to be prepared as an Immediate-Use CSP in the Plexiglas box. Full compliance with USP <797> would require handling in an ISO Class 5 hood if more than two needle punctures are needed. It is okay to keep the box if the following two requirements are met:

  • The box is not compromising the performance of ISO Class 5 compounding area (e.g., laminar airflow hood)
  • The cleaning and disinfection procedures for the compounding area, including the box, as per USP <797> are properly carried out.

Unfortunately, USP <797> requirements do not always mesh well with radiation safety practices, as illustrated by the example above.

Disclaimer

These FAQs reflect the authors' views only. They have not been provided or endorsed by the USP Convention or the USP Expert Committee on Sterile Compounding, nor do they necessarily reflect the views of the authors' institutions, SNM, or any other entities. This document is provided for informational purposes only and is not intended as legal advice. It should not be used to replace the advice of your own legal counsel.

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