Compounding Meeting USP 797 Pharmacy Regulations", (c)
Linda D. Lee, Health Facilities Management, 20 February,
Maintaining the sterility of an environment where
pharmaceuticals are prepared protects both patients and
pharmacy staff. That is why the Food and Drug
Administration (FDA), state boards of pharmacy and
accrediting agencies such as the Joint Commission and
the Pharmacy Compounding Accreditation Board enforce the
standards of the United States Pharmacopeia's (USP's)
General Chapter 797 Pharmaceutical Compounding—Sterile
Preparations, which is commonly known as "USP 797."
First issued in 2004 and revised in 2008, USP 797
established the first comprehensive quality standards
surrounding the design of and procedures used in sterile
compounding areas. As the standards state, they apply to
all persons who prepare compounding sterile preparations
(CSPs) and all places where CSPs are prepared, stored
To comply with USP 797, health facilities professionals
must determine the risk level of the compounding done in
their facilities, perform a practice gap analysis of the
compounding activities and develop an action plan for
compliance action plan should include written procedures
to standardize such tasks as gowning, gloving and hand
washing. Other procedures might cover quality assurance,
sampling protocols, spill cleanup, personnel training
requirements and the regular maintenance of cleaning logs.
Also, compliance action plans should include a formalized
cleaning plan. The main goal of the cleaning plan is to
minimize air particulate contaminations introduced into
the clean room environment by pharmacy staff and the
products staff use. The plan should include scheduled
cleanings of the anteroom and compounding area based on
the classification of the room and surface area, as
designated by the USP 797 guidelines.
Additional tips include the following:
Personnel. Allow only staff specially
trained in high-level disinfection, similar to operating
room housekeeping staff, to clean the clean room. These
employees must be trained in using 70 percent isopropyl
alcohol for cleaning sterile compounding areas.
Housekeeping staff must comply with written procedures,
donning appropriate personal protective equipment before
entering a clean room and never entering outside of
established cleaning times. Make sure pharmacy staff
remove any open products from the clean room before
housekeeping staff enter.
Scheduling. Staff must clean countertops,
shelving, vents, anteroom sinks and storage bin surfaces
daily at the beginning of the work shift prior to
compounding. Pharmacy staff must clean every 30 minutes
during continuous compounding. This means pharmacy staff
should work closely with housekeeping to ensure enough
cleaning supplies (e.g., microfiber cleaning cloths and
wipers) are on hand. Housekeeping staff should clean the
floors each evening. They should clean walls, ceilings and
storage shelving at least monthly. Also monthly, staff
must "terminally" clean the room, similar to surgical
suites. Before terminal cleanings, pharmacy personnel must
guarantee that compounding has been completed for the day.
It can take about two hours to clean a clean room, and one
to two hours to clean the anteroom in two separate
sessions. The use of separate sessions can minimize
workflow disruption. To minimize cleaning time, some
hospitals use wire shelves and minimize anteroom
inventory, limiting them to a four-day supply. The
hazardous drug room has minimal inventory and takes about
one to two hours to clean.
Supplies. In a hospital environment, the
infection control department usually approves clean room
cleansers. High-level disinfectants destroy microorganisms
with the exception of highly concentrated bacterial
spores. Personnel should wear gloves to protect themselves
from exposure to these cleaning agents. Material safety
data sheets must be available for all cleaning agents and
be part of a hospital hazard communication program.
Supplies must be non-shedding and dedicated to the clean
area to prevent contamination from other areas of the
facility. Staff also must clean tools prior to taking them
into the sterile compounding area.
Methods. Staff should work from far to
near, starting at the farthest corner of the room and
proceeding to the door. During the cleaning process, check
for expired medications and products. Staff must clean
countertops, shelving and storage bin surfaces with
germicidal disposable wipes and use a high-level
disinfectant on carts used to transfer products and on the
outer surface areas of the laminar flow hoods. Vents
should be wiped with a clean cloth before the floor is
cleaned. While anti-fatigue mats can be used, they must be
cleaned daily as well. After cleaning the room, have
housekeeping staff document their activity on a log sheet
co-signed by the pharmacist.
Waste disposal. Pharmacy staff should
move trash from the clean room to the anteroom twice
daily. Staff should dispose of sharps in red biohazard
sharps containers and dispose of hazardous waste in
colored containers, based upon regulated waste streams and
hospital policy. Pharmacy personnel should fill and seal
these containers before the housekeeping or environmental
health and safety departments assume responsibility for
USP 797 points out that airborne contaminants are more
likely to infiltrate critical sites than contaminants
found on the floor or surfaces. The action plan should
include environmental sampling to monitor air quality
regularly for viable and nonviable particulates. Table 1
of USP 797 provides particulate matter limits.
In Class 100 or International Organization for
Standardization (ISO) 5 air environments, the particle per
cubic meter must be no more than 3,520 particles per cubic
meter in a size of 0.5 micrometer (um) or larger when
counted at representative locations. Take the measurement
no more than 1 foot away from the work site, within the
airflow, and during filling and closing operations.
Supporting areas where less significant activities occur,
or clean room areas where the laminar flow stations are
located, must meet at least Class 100,000 (ISO 8) air
quality. The activities conducted in supporting clean room
areas determines their classifications. The FDA recommends
that these areas immediately adjacent to the aseptic
processing line meet, at a minimum, Class 10,000 (ISO 7)
standards under dynamic conditions.
Both air and surface samples may be taken. Staff should
remember to document their sample procedures and include
the time of day. The current guidelines recommend
impaction on a media plate for culturable air sampling.
Settling plates, which were referenced in earlier editions
of USP 797, are now specifically discouraged.
Contact plates or swabs should be used to sample the
surfaces of all ISO-classified areas periodically.
Regularly sample clothing, gloves and other gear of
operating personnel. Media-fill tests should be conducted
annually to verify that each person authorized to make
sterile compounds can do so aseptically.
Conduct a formal risk assessment to determine where staff
should sample for viable particles. Chosen sites must
feature multiple locations within each ISO Class 5, 7 and
8 environment and in the segregated compounding areas at
greatest risk of contamination, such as work areas near
the ISO Class 5 environment. Sample locations prone to
contamination during compounding activities and during
other activities such as staging, labeling, gowning and
Sampling must include zones of air backwash turbulence
within laminar airflow workbenches and other areas where
air backwash turbulence may enter the compounding area.
Consider how the sampling method may affect the
unidirectional airflow within a compounding environment.
For low-risk-level CSPs with a 12-hour or less beyond-use
date that are prepared in an ISO Class 5 environment,
sample inside the ISO Class 5 environment and surrounding
Commercial environmental laboratories can help staff
acquire the correct media and establish sampling
protocols. In general, use a microbiological medium for
bacteria or a medium that supports fungal growth for
fungi. Media used for surface sampling must be
supplemented with additives to neutralize the effects of
Some more specific advice includes the following:
Air. Use an impaction sampler to collect
as much air as possible without drying the media. The 2008
revision bulletin suggests a sampling volume of 400 to
1,000 liters of air, but manufacturer recommendations
should be followed.
Surface. Use contact plates or swabs.
When swabbing, cover at least 24 square centimeters (cm2)
but no more than 30 cm2.
Gloved finger. Use contact agar plates to
sample gloved fingertips after compounding CSPs. This
sampling must occur outside of the ISO Class 5
environment. Gloves should not be disinfected with
isopropyl alcohol immediately before sampling. Touch the
agar with the fingertips of both hands to create small
Determine elevated levels of viable colony counts by
consulting USP 797 or chapter 1116 of the USP
Microbiological Evaluation of Clean Rooms and Other
Controlled Environments. Regardless of colony forming unit
(cfu) counts, corrective actions will depend on the type
of microorganisms identified. If highly pathogenic
microorganisms are found, staff must take immediate
action. Assistance from a microbiologist, infection
control professional or industrial hygienist may be
When a cfu count exceeds its action level according to
Table 4 of USP 797, eliminate the problem, clean the
affected area using written procedures as guides and
resample. Watch for data trends to evaluate the overall
control of the environment. If necessary, re-evaluate
personnel, operations and facilities to identify
opportunities for improvement.
Go to the source
Pharmacy regulations vary by state and organization. Even
the seemingly universal USP 797 is open to interpretation.
To ensure compliance, health facilities professionals
should read and interpret the USP 797 standards for