Deciphering USP 795 requirements

For those who own, operate or design hospital pharmacies and privately owned pharmaceutical compounding facilities, the U.S. Pharmacopeial Convention standards USP 797, Pharmaceutical Compounding — Sterile Preparations, and USP 800, Hazardous Drugs — Handling in Healthcare Settings, are well known.

However, a third standard, USP 795, Pharmaceutical Compounding — Nonsterile Preparations, also is significant for professionals involved in pharmacies.

Since it was originally issued in 2000 and most recently updated in 2011, USP 795 has governed non-sterile compounding of both hazardous and nonhazardous drugs. Half of that equation changed with the introduction of USP 800, which governs hazardous compounding for both sterile and non-sterile operations.

Compounding applications

Pharmaceutical compounding is the creation of personalized, customized medications for patients based on exact strength and dosage prescribed by a physician, prepared by a pharmacist in an appropriate environment to maintain purity and avoid contamination. 

Sterile compounding is used for the preparation of drugs that will be injected into patients or inserted into their eyes. In terms of pharmacy facilities, USP 797 provides guidelines for creating an appropriate environment for sterile compounding of both hazardous and non-hazardous drugs, which includes cleanrooms with specified International Organization for Standardization (ISO) standards, specified pressure relationships between rooms, dedicated exhaust in some cases and many other requirements. 

Additionally, USP 800 provides guidelines for sterile compounding of hazardous and non-hazardous drugs. Hazardous drugs are defined by USP as those listed in the “NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings.” (Nonhazardous drugs are those not listed in the publication.) 

Non-sterile compounding is used for the preparation of drugs that will be applied to the skin or swallowed in pill form. In terms of pharmacy facilities, USP 795 provides guidelines for creating an appropriate environment for the creation of these drugs. Additionally, USP 800 provides guidelines for non-sterile compounding of hazardous drugs. 

Pharmacists select between sterile and non-sterile compounding based on how the pharmaceutical product eventually will be administered to the patient. Non-sterile compounding is the most common type of pharmaceutical compounding. It is done in many private pharmacies, as well as in all hospitals. The vast majority of private compounding facilities do non-sterile compounding, but do not do sterile compounding. 

As quoted from USP 795, there are three categories of non-sterile compounding:

Simple: making a preparation that has a USP compounding monograph or that appears in a peer-reviewed scientific journal article that contains specific quantities of all components, compounding procedure and equipment, and stability data for that formulation with appropriate beyond-use dating; or reconstituting or manipulating commercial products that may require the addition of one or more ingredients as directed by the manufacturer.

Moderate: making a preparation that requires special calculations or procedures (such as calibration of dosage-unit mold cavities) to determine quantities of components per preparation or per individualized dosage units; or making a preparation for which stability data for that specific formulation are not available.

Complex: making a preparation that requires special training, environment, facilities, equipment and procedures to ensure appropriate therapeutic outcomes.

Although non-sterile compounding must be done in environments and according to guidelines such as USP 795 to avoid contamination, non-sterile compounding does not need to be done in a cleanroom designed to ISO standards.

Focusing now on USP 795, this standard does have wide applicability, since non-sterile compounding of non-sterile drugs is performed widely by both hospital pharmacies and private pharmaceutical compounding facilities. What follows are key things to know about these standards as they relate to facility design. 

Facilities designed to comply strictly with USP 795 are generally less complicated than those designed to comply with USP 797 and USP 800 because 795 standards don’t deal with sterile compounding and/or hazardous drugs. USP 795 indicates that “areas used for sterile preparations shall be separated and distinct from the nonsterile compounding area.” Now, areas for sterile preparations are covered under USP 797 and USP 800, and require a completely separate ISO suite, so that automatically sets up a separate sterile compounding area. 

To avoid the “cross-contamination,” which the standard warns against, non-sterile compounding should not be done in the sterile ISO suite. Instead, it should be done outside of that suite, either in a separate area with the main pharmacy that is dedicated strictly for this use, or in a separate room altogether (with walls and a door). 

The above area or separate room within the pharmacy should, according to USP 795, “ … provide for the orderly placement of equipment and materials to prevent mix-ups among ingredients, containers, labels, in-process materials and finished preparations, and is designed, arranged and used to prevent adventitious cross-contamination.” 

The designer of this area should work closely with the pharmacy to identify quantity and type of storage and shelving required for equipment and materials, and incorporate that into the program of the room, which will impact the size. Although not mentioned, design of such work areas as counter space and desks, as well as equipment selection, goes part and parcel with the program and design of this space. 

The space should be supplied with two types of water: potable (for hand and equipment washing) and purified water (for use in “compounding nonsterile drug preparations when formulations indicate the inclusion of water … [and] for rinsing equipment and utensils”). 

Addressing these requirements — through one sink or two and which equipment gets washed in potable vs. purified water if there are two sinks — should be resolved in the design process with the health care facility.

In addition to these issues of water type, the standard indicates that “the plumbing system shall be free of defects that could contribute to contamination of any compounded preparation.” Using purified water would address this requirement. 

Also, the standard indicates that the sink(s) shall be “easily accessible to the compounding areas,” but it makes sense to place sinks in the compounding areas if possible. Besides the sink, soap or detergent, an air-drier or single-use towels should be provided.

There are also some general standards for the space, including for waste (“held and disposed in a sanitary and timely manner and in accordance with … standards”); lighting (“well-lighted”); and HVAC (“controlled to avoid decomposition and contamination of chemicals” and “temperature and humidity monitoring … maintained as required for certain components and compounded dosage forms.”)

Further to the previous comments on storage and shelving, “all components, equipment, and containers shall be stored off the floor,” a goal easily accomplished by including a standard raised section in the bottom of any base cabinets. 

The USP 800 effect

The USP guidelines for compounding prior to USP 800 were clear: use USP 795 for non-sterile compounding and USP 797 for sterile compounding. But with the introduction of USP 800, which was written to govern compounding of all hazardous drugs, following the USP standards has become a little more complicated [see table at right].

There is some overlap between the regulations because USP 795 governs all non-sterile compounding (hazardous and nonhazardous) and USP 797 governs all sterile compounding (hazardous and nonhazardous) prior to USP 800.

USP 800 governs all hazardous compounding (non-sterile and sterile), so it must be read in conjunction with the prior standards, USP 795 and USP 797. However, USP 800 does not become official until Dec. 1, 2019, according to a recent extension issued by USP.

How do health facilities professionals handle the current USP guideline stew, which involves three sets of standards where some of the standards are already official (USP 795 and USP 797) and one of the standards (USP 800) won’t be official until Dec. 1, 2019? 

Building a compounding pharmacy now through Nov. 30, 2019, involves a judgment call on the part of the hospital or owner of a private pharmacy in terms of whether to build a facility that:

• conforms solely to the current guidelines (USP 795 and USP 797) or 
• conforms to all three guidelines (USP 795, USP 797 and USP 800), even if USP 800 won’t be official until Dec. 1, 2019.

Knowing that USP 800 will become official on that date, most facilities would want to take USP 800 into account, so that any newly built facility does not become obsolete in terms of conformance to standards after Dec. 1, 2019. However, to cover all bases, it is recommended that any facility contemplating this decision contact its state board of pharmacy to verify its position on this matter.

USP is aware of the overlap among guidelines. Current plans at USP are to issue updated versions of all three guidelines on Dec. 1, 2019 (the revised date when USP 800 becomes official), so that they are coordinated.

Easier to accommodate

Regarding the built environment, USP 795 is much easier to accommodate than both USP 797 and USP 800, because these latter two standards involve creating cleanrooms with ISO requirements, differential pressure relationships between rooms, dedicated exhaust to circumscribed locations on the exterior of the building and, in some cases, sophisticated compounding equipment, which in some cases acts as the exhaust system for the room.

Nevertheless, it is important to understand how USP 795 fits in among the three compounding standards and to be able to create spaces that meet the USP 795 requirements for hospitals and pharmaceutical compounding facilities.

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William N. Bernstein, LEED AP, AIA, is principal at Bernstein & Associates Architects, which has implemented USP 795, USP 797 and USP 800 across the U.S. He can be reached at wb@bernarch.com.