Environmental Monitoring By Angela Yaniv, PharmD

Photo courtesy of Q.I. Medical, Inc

Considerations for Environmental

and Personnel Monitoring

T
he original 2004 version of USP Chapter <797> established require-
ments for environmental monitoring in areas where sterile products
are prepared as well as routine assessment of aseptic technique.
The 2008 revision to the chapter added monitoring requirements
as well as changes to the methodology and frequency for viable air-
borne particle monitoring. The purpose of this monitoring is to ensure particle
control in the cleanroom and to demonstrate, in an objective way, that personnel
comply with aseptic technique, hand and glove hygiene procedures, and cleaning
processes. While meeting these requirements involves a commitment of time and
resources, USP <797> provides a valuable framework of guidelines for ensuring
the safety of sterile products.

Photo courtesy of CriticalPoint, LLC

Temperature and Humidity Control
Monitoring and controlling temperature and humidity in the cleanroom is criti-
cal to ensuring the comfort of garbed personnel as well as minimizing particles.
Individuals shed particles more rapidly when sweating or shivering. Not to men-
tion, a staff member who is too hot is more likely to take gowning shortcuts,
while a staff member who is too cold is more prone to wearing inappropriate
garments for a controlled environment. Humidity also impacts particle control:
High humidity can cause staff members to sweat, and in low humidity condi-
tions, static electricity can affect the movement of particles. For example, when
it is too dry, any residual particles on labels or supply packaging will stick to
gloves and other surfaces instead of settling out.
A comfortable cleanroom temperature is directly related to the extent of gown-
ing required. In our cleanrooms, we require full bunny suits over scrubs in addition
to a mask, hair cover, shoe covers, and gloves, and for personnel compounding
hazardous drugs, a chemotherapy gown and second set of gloves are required as
well. When fully garbed, most of our compounding personnel prefer a tempera-
ture around 65°F (18°C).
Temperature and humidity fluctuations provide a good indication of the perfor-
mance of our air handlers. For example, if a fan belt is worn, we will usually experi-
ence temperature increases of a few degrees. Quickly responding to a temperature
increase by replacing worn fan belts can avert the huge temperature spike that re-
sults when the belt breaks. Initially, this required educating the facilities department
staff, who were not used to complaints when the room temperature was 70°F.
Pressure Differential Monitoring
Monitoring of pressure differential, which is measured in inches of water col-
umn, provides assurance that the cleanroom air is blowing in the right direction
and with sufficient force. Per <797>, pressure differential monitoring devices are
required between buffer areas and ante areas (ISO 7 to ISO 8) and between ante
areas and the general pharmacy environment. Monitoring devices also are neces-
sary between hazardous drug preparation areas and the rest of the cleanroom.
This type of monitoring ensures that clean air is flowing from the cleanest areas
in the cleanroom to the dirtiest. The continuous flow of air away from the com-
pounding area serves to sweep particles away—moving them with the airflow.
Maintaining negative pressure from non-hazardous to hazardous compounding
areas keeps hazardous drug particles from entering the general environment
Sharing fingertip results with an employee in a timely manner and being able
to offer observations of behaviors that can explain growth on the fingertip tests
can be a powerful teaching tool.
since they would have to travel against the airflow. This improves containment
and limits unnecessary exposure.
Differentials that are too low indicate something is wrong with the air supply,
blowers, or other air handling equipment. Differentials that are too high may cre-
ate turbulent airflow in the cleanroom. For positive air pressure differentials, you
should be able to feel the air moving out of the cleanroom when a door or sliding
pass-through is open.
Non-viable Particle Monitoring
Non-viable particle counts are used to verify the air quality classification for pri-
mary engineering controls (PECs), such as laminar flow workstations and bio-
logical safety cabinets, as well as buffer and ante areas. This type of monitoring
is required every six months as part of hood and cleanroom certification as well
as when a PEC is moved and/or when a cleanroom is renovated or altered. This
has been standard practice for decades and is likely sufficient for low-risk com-
pounding operations. However, if you have had a hood fail certification before,
it has probably crossed your mind that there is really no way of pinpointing ex-
actly when the problem started.
For busier medium- and high-risk compounding operations, additional particle
count monitoring outside of normal certification should be considered. This is
particularly critical for open architecture cleanrooms, since it can be difficult to tell
when an individual fan filter unit is not working.
Portable particle monitoring equipment is available. Keep in mind that use
of this equipment requires some staff training and the development of a regular
sampling plan that defines sampling locations, conditions, and frequency. If imple-
mented, the task of particle counting should be a routine assignment.

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 Environmental Monitoring

For larger facilities, monitoring equipment can be installed that will continu- Personnel habits tend to drift over time, and one employee’s bad habit can be
ously monitor particle counts at fixed locations throughout the cleanroom. A con- picked up by others. Fingertip testing lends significant insight on the hand and
tinuous monitoring system ideally should include an alarm with multiple trigger glove hygiene habits of your compounding personnel, and more frequent testing
points determined by the ISO classification of the zone being monitored. allows for issues to be identified quickly and objectively. We draw pictures of the
plates for documentation and to share with the employee when remediation is re-
Viable Airborne Particle Monitoring quired. Sharing the results, including the picture, when growth is found is usually
The 2004 version of USP <797> required weekly sampling for high-risk com- all it takes to get a staff member back on track. The frequency of testing should be
pounding areas and monthly sampling for low- and medium-risk compounding ar- determined based on the type of compounding that you do and the rest of your
eas. That version suggested using either electronic air samplers or passive settling quality assurance program. Currently we test monthly for those staff involved in
plates for sample collection. The use of passive settling plates was a relatively easy high-risk compounding and semi-annually for medium-risk.
and inexpensive option for compliance. Growth on settling plates can indicate
PEC failure or inadequate cleaning, especially in hoods with resident equipment Surface Sampling
such as pumps or vial shakers. However, there is a risk of false negative results, The surface sampling requirement was another new addition to the 2008 revision.
particularly in horizontal airflow environments because with adequate horizontal A variety of surface sampling products are available, including swabs, strips, and
air speed only very heavy particles will settle onto the plates. growth media plates. Where, how, and when to sample should be defined in the
The 2008 revision discusses the shortcomings of collection via settling plates standard operating procedures. Outsourcing this sampling to your certification
and discourages their use. Use of active air sampling devices that collect a fixed vol- company may be a reasonable option to meet the requirement. We incorporated
ume of air and impact it onto the growth media is stated as the preferred method surface sampling as part of the observed media fill competency and the observed
of collection. Appropriate growth media are specified in the revision and include cleaning competency. This provides samples from throughout the cleanroom over
malt extract agar or other appropriate media for the detection of fungi in high-risk the course of the year and it is an objective competency measure for technical staff.
compounding areas. Additionally, the 2008 revision includes suggested action lev-
els for each air quality classification.
The frequency of sampling was reduced to every six months in the 2008 revision, WHERE TO FIND
coinciding with the requirements for PEC and cleanroom certification. Many certi-
fication companies now offer viable air sampling as part of scheduled certification.
Environmental
This provides an easy and cost effective way to meet the minimum requirements set Monitoring Equipment
forth in USP <797>. Air sampling devices can be expensive, and most require annual
recertification. In addition, there is a learning curve involved in operating an air sam- www.pppmag.com/info
pler to prevent accidental contamination of the media by the operator.
Vendor Reader Service Number
Conducting viable airborne particle monitoring every six months gives just a
small snapshot of environmental bio-burden and does not allow for observing Acute Care Pharmaceuticals 31
trends that may indicate cleaning lapses or issues with air filtration. For larger com- B&V Testing Inc 32
pounding operations and all high-risk compounding areas, it is advisable to sample
at least monthly. Bio-Med QC LLC 33
Bioscience International 34
Media-fill Testing
Requirements for media-fill testing did not change in the 2008 revision. Sev- Biotest Diagnostics Corporation 36
eral companies make broth components in a variety of sizes and containers Computer Aided Solutions 37
that can be used to design a media-fill test that mimics the type of compound-
BD—Diagnostic Systems 38
ing performed in your cleanroom. We designed our high-risk media-fill test
to mimic preparation of an intrathecal syringe from a non-sterile powder and Ecolab Healthcare 40
included all relevant equipment and manipulations typical to that type of
Hardy Diagnostics 41
compounding.
Innotech Products, Inc 42
Gloved Fingertip Testing Lab Safety Corporation 43
Gloved fingertip sampling was added as a personnel monitoring requirement in
the 2008 revision. The initial series of required samples is designed to demon- Microbiological Environments 44
strate a new employee’s proficiency at gowning and gloving without contami- Millipore Corporation 46
nating the gloves. Subsequently, fingertip testing is required with each media-fill
test—once a year, at minimum, for medium-risk compounding personnel or Particle Measuring Systems, Inc 47
semi-annually for high-risk compounding personnel. Q.I. Medical, Inc 48
The initial testing is a good opportunity to acclimate new employees to being
Remel 49
mindful of their hands while compounding. It is not always easy to teach staff to
recognize touch contamination risks. Sharing fingertip results with an employee Spectrum Pharmacy Products 51
in a timely manner and being able to offer observations of behaviors that can ex-
Veltek Associates, Inc 52
plain growth on the fingertip tests can be a powerful teaching tool. For example,
it is more effective to tell an employee with contamination on the index finger of PP&P offers more detailed product
their glove that you observed them adjusting their glasses with that finger, rather research at findit.pppmag.com
than simply informing them they failed the fingertip test.

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 Environmental Monitoring

Table 1. Evolution of USP <797>’s Environmental and Personnel Monitoring Requirements

2004 Requirements 2008 Requirements

Measure Specification, Method, and Frequency Specification, Method, and Frequency
Environmental Quality and Particulate Burden
Temperature Appropriate 20°C or cooler, to maintain comfortable
conditions for garbed personnel
Humidity Appropriate Appropriate (in reference to drug storage)
Pressure Differentials Not specified • A pressure gauge or velocity meter is required to monitor pressure
differentials from buffer areas to ante areas and from ante areas
to the general pharmacy environment. The latter must be maintained
between 0.02 and 0.05 inches water column (positive pressure)
• Monitoring between non-hazardous and hazardous compounding
buffer areas with a minimum requirement of 0.01 inch water
column (negative pressure)
• Recording every shift (at least daily), with continuous
monitoring preferred
Non-viable Airborne • Total particle counts assessed for each primary engineering control (PEC) device (laminar flow workstation, barrier isolator, biological
Particle Testing safety cabinet, etc) to maintain ISO 5 conditions at device certification every 6 months and whenever the PEC is relocated
• Total particle counts assessed for secondary engineering controls (cleanrooms) to maintain ISO 7 conditions at cleanroom certification
every 6 months and when renovations occur
Environmental Biological Burden and Personnel Habits
Viable Air Sampling •B  y either electronic air samplers or passive settling plates • Impaction is the preferred method of sampling;
• L ow- and medium-risk compounding areas sampled at least settling plates are discouraged
monthly • Required every 6 months as part of recertification
• High-risk compounding areas sampled at least weekly • Action levels are provided as a guideline for each air classification
• Media is specified and includes malt extract agar for high-risk
compounding areas
Annual or more frequent for low- and medium-risk compounding
Media-fill Testing
Semi-annual or more frequent for high-risk compounding
Initially prior to compounding for patient use
Gloved Fingertip Sampling Not required
and as part of each media-fill assessment
Periodic with locations defined in SOPs
Surface Sampling Not required
and to include all ISO classified areas

In-house Sampling Considerations Conclusion

Typically, pharmacy departments do not purchase and store growth media or
manage incubators, so if you want to build in testing as part of your quality assur-
ance program instead of outsourcing, it is advisable to develop your knowledge of
testing methods and the materials needed. Some common considerations include
ensuring media availability, identifying sourcing options, and determining which
media can be used for the various sampling practices.
Remember, maintaining a small incubator in the pharmacy adds responsibilities:
It must be disinfected on a regular basis and the temperature must be monitored
regularly. In addition, sampling and reporting methods need to be defined. It also
is important to define who is responsible for reading samples. This may be assigned
to a technician or pharmacist and offers an opportunity for skill development and a
new level of accountability.
You might want to consider working with your clinical microbiology lab to
incubate and read samples at specified times. Even if samples are read in the phar-
macy department, clinical microbiology can be a resource for bug identification
when necessary.
Environmental and personnel monitoring requirements may seem burden-
some, especially at the outset. However, these requirements provide an excel-
lent framework for structuring objective measures of environmental quality and
compliance of your personnel in maintaining a safe cleanroom environment.
Keep in mind that USP <797> just provides minimum requirements; depending
on the type and volume of compounding that you do, the size of your controlled
areas, and the number of compounding staff, additional monitoring may be ap-
propriate. With the measures in place at our institution, I am assured that our
clean rooms and staff members are working properly to prevent contamination
of our sterile products. n
Angela Yaniv, PharmD, has been the sterile products manager at Cleveland
Clinic in Cleveland, Ohio, since 2007. She also serves as the interim man-
ager for the Taussig Cancer Institute pharmacy. Angela received both her
bachelor’s degree and doctor of pharmacy degree from the University of
North Carolina.

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