Continuing Education
The 2011 United States Pharmacopeia Chapter <797> Compliance Study:
Discussion of Findings and Strategies for Improvement in the Alternate­site Setting
Kate Douglass, M.S., R.N., A.P.N.C., CRNI®, Eric S. Kastango, M.B.A., R.Ph., FASHP, and Peter Cantor
This INFUSION article is co­sponsored by the National Community Pharmacists Association (NCPA), which is accredited by
the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. NCPA has
assigned 1.0 contact hours (0.1 CEUs) of continuing education credits to this article. Eligibility to receive continuing educa­
tion credits for this article begins May 20, 2012 and expires May 20, 2015. The universal activity number for this program is
207­999­12­146­H04­P. Activity Type: Knowledge­Based.
This continuing nursing education activity was approved by the Virginia Nurses Association, an accredited approver by
the American Nurses Credentialing Center’s Commission on Accreditation.
The CNE approval number for this activity is 12­05­02S.
VNA has assigned 1.0 contact hours (0.1 CEUs) of continuing education credits to this article. Eligibility to receive continuing education cred­
its for this article begins May 10, 2012 and expires May 31, 2014.
This continuing education article is intended for pharmacists, nurses, and other alternate­site infusion professionals. Participants must
receive a passing score of 70% or higher and must complete the evaluation questions subsequent to the online post­test in order to receive
credit for this program activity.
Approval as a provider refers to recognition of educational activities only and does not imply Accreditation Council for Pharmacy Education, National
Community Pharmacists Association, ANCC Commission on Accreditation or the Virginia Nurses Association approval or endorsement of any product.
This continuing education activity is not underwritten or supported by any commercial interests.
Learning Objectives
After reading this article, the participant should be able to:
1. Recall the 2011 top domains of sterile compounding compliance for the alternate site community
2. List the 2011 lowest domains of sterile compounding compliance that apply to the majority of the alternate site study participants
3. Correctly summarize the requirements of USP Chapter <797> with regard to the areas of lowest compliance in the alternate site population
4. Describe in detail the strategies and procedures to improve specific sterile compounding practices as they relate to the alternate­site
industry’s identified weaknesses
About the Authors
Eric Kastango, R.Ph., M.B.A., FASHP, is President and CEO of Clinical IQ, LLC, and serves on the USP Compounding Expert Committee (2010­
2015). He received a Bachelor’s degree in Pharmacy from the Massachusetts College of Pharmacy and Allied Health Sciences and an M.B.A.
from the University of Phoenix. Since 1980, he has served in a number of different of roles, including Vice President of Pharmacy Services for
Coram Healthcare and managing an FDA­registered manufacturing operation for Baxter Healthcare. Kastango is a Fellow of the American
Society of Health­System Pharmacists (ASHP) and is an active member of the Institute for Environmental Sciences and Technology, the
Association for Professionals in Infection Control and Epidemiology, and the American Society for Quality. Kastango can be reached at
[email protected] or at 973­765­9393.
M AY/J U N E 2 0 1 2
Kate Douglass, M.S., R.N., A.P.N.C., CRNI®, is the President of Performance Strategies, LLC. She received her Bachelor of Science in Nursing
from Villanova University and a M.S. from Rutgers. Licensed as an Advanced Practice Nurse, Douglass has over 30 years of health care indus­
try experience in both clinical and executive management positions. She served as the Senior Vice President of Clinical Operations for Coram
Healthcare and was the COO of SoluNet, LLC, a pharmacy provider of compounded sterile preparations and an FDA­registered manufacturer.
Douglass is a past Chair of NHIA’s Education Committee and serves on the editorial review board for the Journal of Infusion Nursing. Douglass
can be reached at [email protected] or at 201­251­4331.
1
Peter Cantor is President of CriticalPoint, LLC. He has more than 10 years of experience in pharmacy product development, sales, and edu­
cational training. Most recently, Cantor worked for ASHP as Manager of Electronic Product Development. He has a Bachelor’s degree in
Secondary Education from The Ohio State University. Cantor can be reached at [email protected] or at 240­238­4352.
Author Disclosure Statement: Eric Kastango, R.Ph., M.B.A., FASHP; Kate Douglass, M.S., R.N., A.P.N.A., CRNI®, and Peter Cantor declare no
conflicts of interest in any product or service mentioned in this program, including grants employment, gifts, stock holding, and honoraria.
This article contains no mention of off­label drug use.
Continuing education credit is free to NHIA members, and available to non­members for a nominal processing fee. To
apply for nursing or pharmacy continuing education, go to www.nhia.org/CE_Infusion and follow the online instructions.
Continuing Education
www.nhia.org/CE_Infusion
S
Highest Compliance Scores
As we reported in the March/April 2012 issue of INFUSION, the
alternate­site population had an overall compliance score of
83.5% which was the third highest among the cohort
groups—exceeded only by pharmacy central fill/outsource
providers and FDA­registered manufacturers (see Tables 1 and
2 on pages 9­11 for compliance scores by domain and best
practices most often performed by providers). Some content
domains applied to a smaller subset of providers, but the
domains with compliance scores of 90% or more that applied
to all 122 alternate­site provider participants were:
• Quality Management: Non­Viable Particle Testing
• Personnel Media­Fill Challenge Testing
• Final Release Checks
• Compounding Facility Management: Temperature
and Humidity Monitoring
• Inventory Storage and Handling/Delivery of
Compounded Sterile Products (CSPs)
• Aseptic Technique
• Single­ and Multiple­Dose Vials
• Initial and Ongoing Training and Competency
Measurement
• Hand Hygiene and Garbing
The study team expected that this population would
score higher in overall compliance than hospitals,
because the home infusion and ambulatory infusion
center settings had the ability to build state­of­the art
facilities as a competitive differentiator. These facilities
have typically been built from “scratch” in new loca­
tions and not “land locked” in an older facility like many
hospital pharmacy departments. These high­compli­
ance domains are also consistent with our observations
of sterile compounding in a variety of work settings.
The high compliance rate of 92% for the Single­ and
Multiple­Dose Vial domain is an interesting finding given
the amount of controversy and debate about the use of
single­dose containers for multiple patients. Driven by
both the drug shortage and the constant effort to reduce
waste, this topic is being hotly debated on many listservs
today. The issue is that manufacturers often do not pack­
age their drugs in single­dose containers based on what
would be a normal dose for a single patient. To eliminate
wasted drug, many pharmacies use single­dose containers
as they would use pharmacy bulk packages.
According to the USP, a single­dose container “is a sin­
gle­unit container for articles or preparations intended for
parenteral administration only. It is intended for a single
use.”3 Single­use containers are intended to support one
puncture only and they do not contain preservatives; how­
ever, many pharmacies are retaining single­dose vials with
residual drug to be used on subsequent patient orders.
Studying Compliance
The first annual United States Pharmacopeia Chapter
<797> Compliance study was conducted in spring 2011
and the overall results summary published in Pharmacy
Purchasing & Products (available online at: www.ppp­
mag.com/article/985/October_2011_Cleanrooms_Com
pounding/The_2011_USP_797_Compliance_Study/).
The March/April 2012 issue of INFUSION focused on
reporting the demographic and high­level compliance
data from the alternate­site population.
M AY/J U N E 2 0 1 2
terile compounding has been likened to a rope in
which many intertwined threads—or processes—
combine to create strength. With the guiding prin­
ciple of patient safety, the pharmacy profession has
been striving to improve upon each of the processes that
contribute to the preparation of compounded sterile
products used to treat patients. Most notable are guide­
lines put forth in the United States Pharmacopeia (USP)
Chapter <797> in 2004, and revised in 2008, which serve
as the industry standard today. While great strides have
been made, and patient safety enhanced overall, isolat­
ed reports of improper preparation and patient harm as
recent as 2011 remind us that compliance with USP <797>
is a top priority for every practitioner and provider orga­
nization.1 Given that directive, just how is the alternate­
site field doing in terms of true, systematic compliance?
Data from a recent study of pharmacies show that
the alternate­site provider population was among the
groups with the highest overall compliance with United
States Pharmacopeia (USP) Chapter <797> (see box,
this page for more).2 However further review demon­
strates several areas where compliance with USP <797>
and patient safety can be improved. This article reviews
the chapter content domains that scored the highest
and lowest compliance among alternate­site providers;
summarizes the requirements of the chapter with
regard to areas of low compliance; and provides strate­
gies and resources to assist home infusion providers in
achieving greater degrees of regulatory compliance.
2
www.nhia.org/CE_Infusion
The chapter has unintentionally created some contro­
versy since the USP definition of single­dose containers
in the General Notices section of the USP­NF states that
they are used for one patient. By stipulating in Chapter
<797> that a single­use vial may be used up to six hours
after the initial vial puncture when exposed to ISO Class
5 or cleaner air, by definition then the single­dose vial
could be used for multiple patients.
Continuing Education
CSPs shall also be subjected to manufacturers’ recom­
mended integrity test, such as the bubble point test.”3
See page 7 for knowledge and compentencies
Airflow/Pressure Monitoring
Lowest Compliance Scores
At first glance, some of the content domains with the low­
est compliance scores might appear unconcerning. For
instance, overall compliance scores of 78% for Hazardous
Drug Compounding and 80% Facility Design do not appear
to represent a significant level of non­compliance.
However, it is important to recognize that overall scores
for a domain do not represent the score for individual items
within that domain. The Hazardous Drug domain repre­
sents 13 individual items with scores ranging from 34% to
100%. The General Facility domain represents 10 items with
scores ranging from 53% to 93% see Table 3 on page 11). The
remainder of this article focuses on specific items from the
following domains:
• Filter Integrity (bubble point) Testing
• Airflow and Pressure Differential Monitoring
• Gloved Fingertip Sampling
• Viable Air Sampling
• Sterility Testing
• Surface Sampling
• Hazardous Drug Compounding
• Facility Design
M AY/J U N E 2 0 1 2
Filter Integrity Testing
3
One of the items with the lowest compliance related to fil­
ter integrity testing. Only 39% of the 74 respondents who
used a 0.22­micron filter during compounding, indicated
that they perform a filter integrity (bubble point) test.
This low compliance rate may be, in part, due to some
ambiguity within the item itself. The question sequence
assumes that if a 0.22­micron filter was used, it was solely
for the purpose of sterilization, which may not be the case.
This item has been modified in the 2012 survey to further
clarify what is being asked.
Participants who indicated that they perform high­risk
compounding and sterilize the resulting CSPs by filtration
were asked whether they perform filter integrity tests
(e.g., bubble point) at the conclusion of the compounding
procedure. Only 62% of them indicated that they did.
This finding is troubling because participants didn’t
seem to have a clear understanding of when and how to
use filters. Filters must be used per manufacturer specifi­
cations (volume of filtrate and compatibility with drugs
and solutions). Integrity testing of sterilizing filters is a
critical quality assurance component and required by
USP <797>, which states: “Filter units used to sterilize
Participants who indicated that they had both ante and
buffer areas (105 total) were asked if they measured pres­
sure differential or airflow velocities daily. Only 55% of
these locations performed daily pressure differential mon­
itoring. USP <797> says that a “pressure gauge or velocity
meter shall be installed to monitor the pressure differen­
tial or airflow between the buffer area and ante area and
the ante area and the general environment outside the
compounding area. The results shall be reviewed and doc­
umented on a log at least every work shift (minimum fre­
quency shall be at least daily) or by a continuous recording
device. The pressure between the ISO Class 7 and general
pharmacy area shall not be less than 5 Pa [0.02 inch water
column (w.c.)]. In facilities where low­ and medium­risk
level CSPs are prepared, differential airflow shall maintain
a minimum velocity of 0.2 meter/second (40 fpm)
between buffer area and ante area.”3
One barrier to compliance might be that older com­
pounding facilities did not have a Magnehelic® gauge
installed when built, but there is a fairly easy, inexpen­
sive, and quick fix. One Magnehelic® gauge runs between
$55­85 (not including the cost of the tubing and mount­
ing bracket). Add a few hours labor for the installation of
each gauge. Most facilities that have an ISO 7 buffer area
and an ISO 8 ante area will require two gauges. Your
cleanroom certifier can install these gauges so you can
measure and document pressure differentials between
buffer, ante, and general pharmacy areas.
Gloved Fingertip Sampling (GFS)
The overall score for the Gloved Fingertip Sampling
(GFS) domain was 65%. Participants who report
low/medium­risk level compounding versus high­risk
level compounding were equally compliant (see Exhibit
1) with the requirement to perform GFS at the time of
their media fill qualification annually or semi­annually,
respectively. There was lower compliance with the ini­
tial GFS, which is an integral part of the garbing compe­
tency. Several factors may be at play here.
GFS was one of the requirements added in 2008—as
per USP, “all compounding personnel shall successfully
complete an initial competency evaluation and gloved
fingertip/thumb sampling procedure (0 cfu) no less than
three times before initially being allowed to compound
CSPs for human use.”3 The rationale was to test whether
the compounder was able to successfully don sterile
gloves without contaminating them. Note that for our
survey, the Study Team added “including supervising
pharmacists” to the survey question because it is our
belief that pharmacists supervising sterile compounding
should be competent to perform all of the duties they
are responsible for overseeing. It is also apparent that
the procedure for performing GFS correctly is unclear
since 71% of alternate­site providers reported complying
with the procedure for initial sampling—the study team
has observed this in practice. The sample needs to be
taken before compounders’ gloves would normally be
disinfected with sterile 70% IPA, or false negatives will
occur. It’s also important to remember to change sterile
gloves after the sample is taken and before compound­
ing is begun. A detailed sample GFS policies and proce­
dures, a GFS log form, and an online GFS lesson are avail­
able at www.pppmag.com/article/991/October_2011_
Cleanroms_Compounding/Samples_of_GFS_Policies_an
d_Procedures/.
Viable Air Sampling
The 2008 revision of USP <797> also requires that viable
air sampling be performed using two different types of
media (a general growth media and another that sup­
ports the growth of fungus) for high­risk compounding
only. The overall compliance score for all items in this
domain for the alternate­site population was 70%. This
domain contained five items, and by far the lowest com­
Exhibit 1
Gloved Fingertip Sampling
72%
High-Risk
(n=32)
Ongoing GFS at least semi-annually with media
72%
All Alt-Site
(n=122)
GFS samples taken before sterile 70% IPA
All Alt-Site
(n=122)
Low/MediumRisk (n=90)
0%
10%
20%
30%
40%
71%
52%
50%
60%
70%
80%
90%
100%
www.nhia.org/CE_Infusion
pliance score (51%) involved the use of two different
growth media (see page 8 for graph). The presence of
fungus and other related microbial bioburden is prob­
lematic for all risk levels of compounding. Providers
should consider including the use of this media when
their next viable air sampling is being performed. It’s like­
ly that USP will expand the two media requirement to all
risk levels as the 2010­2015 Compounding Expert
Committee continues to refine and clarify the ongoing
questions about the chapter.
Sterility Testing
The requirements surrounding sterility testing are wide­
ly misunderstood as well. To determine if a participant
was required to perform sterility testing, the Study
Team developed a non­scored item in the General
Compounding domain. Of the 34 pharmacies required
to perform sterility testing per USP <797>, only 53%
complied. This item also asked about bacterial endotox­
in testing (BET), but since BET applied to so few loca­
tions, it will not be discussed in this article.
USP <797> requires that sterility testing be per­
formed when the default beyond use dates (BUDs) are
exceeded. The vast majority of alternate­site providers
required to do sterility testing in this sample, were
required to do so based solely, or partially, on BUD
assignment (30 of 34). Only 50% of the 30 pharmacies
required to do sterility testing based on their practice of
exceeding the default BUDs did so.
It is important to understand that performing a sterility
testing according to USP Chapter <71> requirement is a
destructive, expensive, and complicated test that has a 14­
day incubation period. The preferred method of sterility
testing is membrane­filtration and not direct inoculation.
While USP Chapter <71> stipulates that a “method not
described in the chapter may be used if verification results
demonstrate that the alternative is at least as effective
and reliable as the USP Membrane Filtration method or
the USP Direct Inoculation of the Culture Medium method
where the Membrane Filtration method is not feasible,”
it’s a daunting task for any single provider to generate
enough data to be statistically significant.3
Another common misconception about sterility testing
is that it can be performed on one or several “representa­
tive” batches of a particular CSP. Some providers have
adopted a methodology similar to media fill process valida­
tion—where a particular compounding process is verified
by media fill simulation every six months—performing
sterility testing on a predetermined number of units in a
predefined set of batches. They mistakenly assume that if
the tests demonstrate a negative finding (no growth), then
all other batches of that CSP made in the same manner will
also be sterile. This practice is not acceptable. Sterility test­
ing is required on each and every batch of CSPs when the
default BUDs of USP Chapter <797> are exceeded.
M AY/J U N E 2 0 1 2
Continuing Education
4
www.nhia.org/CE_Infusion
The term ‘sterile’ is an absolute, indicating a complete
absence of viable organisms. Sterility can therefore only
be demonstrated by testing every CSP for the presence
of viable growth. As stated earlier, sterility testing is an
expensive and destructive process. It is impossible for
any test method to demonstrate with absolute certain­
ty that any particular lot of CSPs is sterile, since 100% of
the batch would need to be tested. As such, the idea
that a CSP is sterile must be viewed in the context of its
statistical probability of being sterile.
USP Chapter <71> describes methods by which sterility is
asserted, involving either the application of end product
testing to a statistically appropriate number of samples
from each lot, or the validation of an aseptic filling process
with a large number of test articles. The probability of
detecting a contaminated unit from any single sterility test
is impractically low. Is sterility testing per USP <71> require­
ments a perfect test? Certainly not, but it is the best test
currently available to detect gross contamination.
M AY/J U N E 2 0 1 2
Surface Sampling: A Personnel,
Process, and Environmental Metric
5
In terms of environmental sampling, surface sampling is
more of a personnel and process metric than a facility met­
ric. Surface sampling measures the degree to which work
practices—such as daily cleaning, disinfecting the critical
work surface during compounding, and frequent disinfec­
tion of gloved hands—are effective in achieving a clean
work surface in the direct compounding area (DCA) as well
as other areas in the cleanroom. Though it measures envi­
ronmental bioburden, if the facility’s primary and sec­
ondary engineering controls (PEC and SEC) are function­
ing properly, employee work practices have the greatest
impact on this metric. Although alternate­site providers
achieved an overall compliance score of 75% for this
domain, two domain items had compliance rates below
70% (see Exhibit 2). Only 77 locations (63%) indicated that
surface sampling was performed at the conclusion of com­
pounding and before the area is cleaned with an appropri­
ate disinfectant. When surface sampling is performed, it
must occur at the conclusion of the compounding day or
shift in order to capture the worst case scenario, and per­
formed in the locations detailed in the environmental sam­
pling plan (ESP). The chapter does not specify exactly how
often to perform surface sampling but states it is to be
“performed in all ISO­classified areas on a periodic basis…
and shall be done at the conclusion of compounding…
Locations to be sampled shall be defined in a sample plan
or on a form.”3 Seventy­eight percent (78%) indicated they
have a written ESP that identifies where viable air sam­
pling and surface sampling will occur.
Surface sampling can be combined with personnel
media fills and GFS as a means of demonstrating staff
proficiency in the critical areas of aseptic technique,
proper component disinfection practices, and cleaning
Continuing Education
activities. Factors to be considered in the frequency and
timing of surface sampling include compounding risk
level (more frequently when performing high­risk level)
and tenure of compounding staff (more frequently
when staff are new, inexperienced, or when there is lit­
tle testing history). Surface sampling can be used as a
means of verifying that routine cleaning and disinfec­
tion practices are being properly performed, and can be
instructive when performed randomly (i.e., sampling
occurring monthly should not take place at the same
time of the month and, optimally, without warning).
In addition to tryptic soy agar medium (with polysorbate
and lecithin added to neutralize cleaning agents [TSApl]),
locations that perform high­risk compounding are required
to use an additional media that supports fungal growth—
particularly yeasts and mold—such as malt extract agar
(MEA). Only 31% of locations doing high­risk compounding
comply with this requirement.
Hazardous Drug Compounding
There were 95 providers who reported that they per­
form hazardous drug (HD) compounding. Some HD
chapter requirements apply only to those who com­
pound greater than low­volume HDs (not more than one
HD CSP per day, for the purposes of this study). Only 52
locations in our study were required to meet all the USP
Chapter <797> HD requirements. Overall, the alternate­
site group averaged 78% compliance for all 16 items in the
HD Compounding domain. Of the six items for which
there was a group score of less than 75%, three of the
items applied only to locations that did not meet the low­
volume exemption (see page 8 for graph). All of these
items relate back to locations that did not have or need
a negative pressure HD compounding room.
Identification of a separate area where a biological safe­
ty cabinet (BSC) or compounding aseptic containment iso­
lator (CACI) is located is a sufficient strategy only for facili­
ties preparing low volumes of HDs. When the BSC and
CACIs are not located in a negative­pressure room, the use
of closed system transfer devices (CSTDs) is required.
However, regardless of the number of HDs prepared, these
drugs must be stored separately from other inventory to
prevent or reduce the likelihood of contamination and per­
sonnel exposure, in an area under negative pressure (0.01”
w.c. negative) and at least 12 air changes per hour (ACPH)
to dilute and remove any airborne contaminants.
The remaining three items in the domain with poor com­
pliance relate to employee education and training regarding
the handling of HD—a requirement that applies to all orga­
nizations that prepare HDs, regardless of volume. The
requirement to obtain written confirmation from each
employee of reproductive age that they understand the risk
of handling HDs, added in the 2008 revision, was the item
with the lowest overall compliance (34%) for the alternate­
site provider group. Compliance may be low because the
acknowledgement requires that each pharmacy refer to
other documents and practices that have to be implement­
ed (for a sample form, go to http://www.pppmag.com/doc­
uments/V8N10/CC/PDFs/HazDrugRisk_Acknowledg.pdf).
Facility Design
All participants were asked about the design of their sterile
compounding facility. The alternate­site participants scored
an 80% overall for the 10 items in this domain, but there are
three areas of significant non­compliance which can be fair­
ly easily and inexpensively remedied (see Exhibit 3):
• Line of Demarcation Participants were asked if their
Exhibit 2
Surface Sampling
All Alt-Site
(n=122)
Appropriate cleaning after sampling
All Alt-Site
(n=122)
Conducted at conclusion of compounding
88%
63%
All Alt-Site
(n=122)
Performed using contact plate and/or swab rinse
All Alt-Site
(n=122)
Occurs regulary and frequently as per Environmantal
Sampling Plan
Low/MediumRisk (n=90)
1 type of plate is used
2 types of plates
are used
High-Risk
(n=32)
0%
20%
84%
78%
73%
31%
40%
60%
80%
100%
Exhibit 3
Facility Design
All Alt-Site (n=122)
Line of demarcation in ante area or
segregated compounding area
58%
Ceiling panels that are caulked and impervious
71%
Hands-free sink and soap dispenser 53%
in ante area
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
www.nhia.org/CE_Infusion
location has a line of demarcation in the ante area or
segregated compounding area that separates the dirty
area from the clean area. Although USP <797> implicit­
ly refers to the purpose of a line of demarcation, an
official definition was omitted from the 2008 revision.
As such, 58% of respondents said their location com­
plied with this design feature. The current chapter
says, “A line of demarcation defining the segregated
compounding area shall be established. Materials and
garb exposed in a patient care and treatment area
shall not cross a line of demarcation into the segregat­
ed compounding area.”3 A line of demarcation serves
as a point for cart and material exchange (clean
cart/dirty cart) and a transition point where the garb­
ing procedure (e.g., donning of shoe covers) starts.
The exact placement will depend upon the location of
your sink (on the clean side of the line of demarcation)
in the ante area as well as your specific garbing order.
Many pharmacies have had great success installing a
line of demarcation about “halfway” or some measure
across the ante room so that they have enough room
to come into the ante room with a “dirty cart” and to
don their shoe covers and hairnets. The line can be
indentified by integrating a different colored sheet
within the vinyl flooring or with cleanroom tape.
• Ceilings Caulked Ceilings should be “made of panels
that are impervious and hydrophobic and are
caulked around the perimeter of each to seal them
to the frame.”3 Though 71% of those with clean­
rooms comply, this requirement gets a lot of push
back. The chapter does not permit the use of tile
clips. Ceiling tiles must be caulked in place and
sealed, especially in a negative­pressure buffer area
so that “dirty air” is not brought into this space.
• Hands­Free Controls for Water and Soap Dispensing
Facilities have been slower to adopt hands­free con­
trols for water and soap. Slightly less than half of the
alternate­site participants (47%) reported that their
location did not comply with this item. Installation of
foot or knee controls for water is becoming more com­
mon and costs approximately $500, including labor.
Hands­free soap dispensers range from $20­$400 each,
with many acceptable models costing less than $100.
• Smoke Studies Of the participants with buffer areas,
nearly half (48%) reported that they did not comply
with smoke study requirements to verify unidirection­
al airflow and sweeping action over and away from the
critical compounding area once PECs were in place.
Although this item is from the Primary/Secondary
Engineering Controls domain, it relates to Facility
Design and is of note because of its low compliance.
Smoke testing (normally when the room is initially
commissioned), allows visual validation that the facility
is functioning as designed. Most cleanroom certifiers
M AY/J U N E 2 0 1 2
Continuing Education
6
www.nhia.org/CE_Infusion
can perform smoke testing, although rates vary consid­
erably depending on the extent of the testing. Ask your
certifier what medium they use when performing a
smoke test. Water vapor or CO2­based fog machines are
no longer acceptable because the effluent (“smoke”) is
heavier than air and may not properly illustrate airflow
patterns. One FDA official stated that the water or CO2
vapors “drop like a rock and mask updrafts and turbu­
lence.”4 Many vendors use theatrical smoke generators
with some form of ethylene glycol, which will leave a
film. Regardless of the agent used, a complete room
clean (all surfaces including floor, walls, and ceiling)
should be conducted after smoke testing. Once you ver­
ify that the room is functioning as designed, further
testing is not necessary unless the PECs are changed.
Most vendors will provide a video of the smoke testing
as documentation of the event if you request it. This
video can be a powerful training resource for your staff
because it allows them to visualize the unidirectional air­
flow sweeping away from the compounding area. The
authors can speak to the power of this visual example—
it will deepen your staff’s understanding of the role of
primary and secondary engineering controls and how to
achieve proper aseptic technique by using “first air.”
Conclusion
USP Chapter <797> has had a positive impact on sterile
compounding practices and is an effective patient safety
practice. The alternate­site industry should be congratu­
lated on its early adoption of many of the requirements
Continuing Education
in the chapter. By and large, the home infusion providers
embraced good compounding practices long before they
became USP <797> requirements. However, ongoing vig­
ilance and focus is needed. Quality in sterile compound­
ing practice is a journey and not a destination. We need
to challenge ourselves and our organizations to continue
to look for ways to constantly improve sterile com­
pounding practices and patient safety. We must be com­
mitted to identifying effective ways to communicate the
requirements of the chapter to all parties involved; edu­
cate managers and administrators; be committed to
staff development; and efficiently implement all items of
this important standard.
References
1.
Institute for Safe Medication Practices (ISMP). Parenteral
nutrition­related deaths and a cluster of bacterial endoph­
thalmitis call for compounding pharmacy oversight ISMP
Newsletter
July
27,
2011.
Available
at:
www.ismp.org/Newsletters/acutecare/articles/A3Q11Action.asp
(accessed 5/12/2012).
2. Douglass K, Kastango, et al. The 2011 USP <797>
Compliance Study. Pharmacy Purchasing & Products.
October 2011:8(10);8.
3. United States Pharmacopeial Convention, Inc. <797>
Pharmaceutical Compounding—Sterile Preparations.
United States Pharmacopeia 34–National Formulary 29.
Rockville, MD: US Pharmacopeial Convention, Inc.; 2011.
4. Wagner, James. Personal email correspondence to Kate
Douglass on March, 9, 2012.
Filter Integrity (Bubble Point) Testing Knowledge and Competencies
Knowledge Competencies
1.
2.
3.
4.
5.
Describes purpose of a filter and the rationale for filter integrity testing.
Identifies when filter integrity testing is performed.
Describes what pounds per square inch (PSI) value shows that a filter has failed the filter integrity test.
Describes procedural mistakes or other circumstances that can result in a false failure of the filter.
Describes the actions to take should a filter fail the test.
M AY/J U N E 2 0 1 2
Skill Competencies: Employee is observed during sterility testing
7
1. Gathers supplies and records the filter part and lot numbers.
2. Wets the filter to be tested with the appropriate fluid (water for hydrophilic filters, alcohol for hydrophobic filters)
making certain that the filter is thoroughly and uniformly wet and that all pores are filled with the wetting fluid.
3. Places the wetted filter into the appropriate housing.
4. Connects the outlet fitting from the compressed air regulator to the upstream side of the filter to be tested.
5. Connects a piece of flexible tubing from the downstream port of the filter to be tested into a beaker of water.
6. Starting from zero pressure, slowly increases the pressure and observes the submerged end of the tubing
until rapid continuous bubbling is observed.
7. Correctly notes the “bubble point” (when bubbles produced from the outlet tubing at a steady rate).
8. Records the pressure to the nearest 0.5 PSI and completes all documentation as required in applicable policy
and procedure.
9. If the filter fails, opens the filter housing to check that the filter is installed correctly on the housing and
retests.10. When testing is complete, discards filter and supplies appropriately.
Continuing Education
Hazardous Drug Compounding
Volume - 400 - 1,000 liters
74%
All Alt-Site (n=122)
Recleaned and sampled if action level exceeded
Volume device used
75%
70%
Perfermed at least semi-annually
0%
10%
20%
30%
Low Volume (n=52) All HD Locations(n=95)
Viable Air Sampling
40%
80%
51%
50%
60%
www.nhia.org/CE_Infusion
70%
80%
90%
100%
Successful competency assessment (annually) 64%
72%
Documented training and testing (annually)
of risk awareness
34%
Seperate and dedicated area for HD
HD Storage in negative
pressure room
46%
Storage has appropiate exhaust
0%
10%
20%
30%
62%
40%
52%
50%
60%
70%
80%
90%
100%
Filter Integrity (Bubble Point) Testing Knowledge and
Competencies
Knowledge Competencies
1. Describes purpose of a filter and the rationale for filter integrity testing.
2. Identifies when filter integrity testing is performed.
3. Describes what pounds per square inch (PSI) value shows that a filter has failed the filter integrity test.
4. Describes procedural mistakes or other circumstances that can result in a false failure of the filter.
5. Describes the actions to take should a filter fail the test.
M AY/J U N E 2 0 1 2
Skill Competencies: Employee is observed during sterility testing
1. Gathers supplies and records the filter part and lot numbers.
2. Wets the filter to be tested with the appropriate fluid (water for hydrophilic filters, alcohol for hydrophobic fil­
ters) making certain that the filter is thoroughly and uniformly wet and that all pores are filled with the wet­
ting fluid.
3. Places the wetted filter into the appropriate housing.
4. Connects the outlet fitting from the compressed air regulator to the upstream side of the filter to be tested.
5. Connects a piece of flexible tubing from the downstream port of the filter to be tested into a beaker of water.
6. Starting from zero pressure, slowly increases the pressure and observes the submerged end of the tubing until
rapid continuous bubbling is observed.
7. Correctly notes the “bubble point” (when bubbles produced from the outlet tubing at a steady rate).
8. Records the pressure to the nearest 0.5 PSI and completes all documentation as required in applicable policy
and procedure.
9. If the filter fails, opens the filter housing to check that the filter is installed correctly on the housing and retests.
10. When testing is complete, discards filter and supplies appropriately.
8
www.nhia.org/CE_Infusion
Continuing Education
M AY/J U N E 2 0 1 2
Table 1
9
Alternate­site Provider Domain Compliance Scores
Percent
Allergen Extracts as CSPs (subset sample size = 1)
100%
Quality Management: Non­Viable Particle Testing
97%
Sterilization Methods (subset sample size = 32)
97%
Personnel Media­Fill Challenge Testing
95%
Final Release Checks
93%
Compounding Facility Management: Temperature and Humidity Monitoring
93%
Inventory Storage and Handling/Delivery of CSPs
92%
Aseptic Technique
92%
Single and Multiple­Dose Vials
92%
Initial and Ongoing Training and Competency Measurement
91%
Hand Washing and Garbing
90%
Steam Sterilization (subset sample size = 5)
88%
Beyond Use Dating
87%
Quality Management: Patient/Caregiver Training
87%
Sterilization by Filtration (subset sample size = 32)
85%
Compounding Facility Management: Cleaning and Disinfecting
84%
Quality Management: General
83%
Primary/Secondary Engineering Controls
80%
Compounding Facility Management: Equipment Calibration
80%
General Facility Design
80%
Hazardous Drug Compounding (subset sample size = max of 95)
78%
Quality Management: Environmental Sampling Program
77%
Quality Management: Surface Sampling ­ A personnel metric
75%
Sterility Testing (subset sample = 18 who do sterility testing though 34 should)
73%
Quality Management: General Viable Air and Surface Sampling Considerations
73%
Bacterial Endotoxin Testing (subset sample size = 5)
70%
Quality Management: Viable Air Sampling ­ A facility metric
70%
Sterilization by Dry Heat (subset sample size = 4)
69%
Quality Management: Incubation
67%
Gloved Fingertip Sampling
65%
CSPs for Immediate Use (subset sample size = 30)
65%
Low Risk Level CSPs with 12 Hour or Less BUD (subset sample size = 4)
65%
Compounding Facility Management: Airflows/Pressure Differential Monitoring
55%
Filter Integrity Test (subset sample size = 74)
51%
Depyrogenation by Dry Heat (subset sample size = 3)
50%
Grand Total 84%
Note: Subset sample sizes are identified when items in the named domain did not apply to all participants. In some cases,
within domains, the sample size was further subdivided (i.e., HDs had a maximum of 95 locations that compound HDs but
other questions applied to even smaller subsets like those whose compounding is limited to small volume.
Continuing Education
www.nhia.org/CE_Infusion
Highest Scoring Items that Apply to Majority of Alternate­site Providers
Compliance
Sample*
The compounding location takes action to ensure that food, drinks, and contaminated sup­
plies/equipment do not enter the ante and cleanroom (buffer) areas.
100%
122
Compounding personnel arrange items at least 6 inches inside of aseptic work area such as
an LAFW.
100%
122
Hazardous CSPs and hazardous drug wastes are disposed of in a manner that complies with
local, state and federal regulations.
100%
95
The organization routinely inspects prescription orders, labels, compounding documentation
and expended materials to verify that the correct identity and amounts of ingredients, asep­
tic mixing and sterilization, packaging, labeling and expected physical appearance are consis­
tent with expectations before they are dispensed.
100%
122
Are multiple dose vials discarded 28 days after initial puncture (or as directed by the manu­
facturer)?
99%
122
Compounding personnel remove waste or unused supplies with minimal in­and­out motion.
Partially used multi­dose vials are dated and initialed outside of the ISO Class 5 work area.
99%
122
Controlled room, controlled cold and controlled frozen environments in the pharmacy and
other areas (e.g. where solutions and drugs are stored) are monitored and conform to USP
temperature requirements for that storage type.
99%
122
Syringes, needles and tubing remain in their individual packaging and are only opened in ISO
Class 5 area.
99%
122
Storage of finished CSPs and drug components is separate from food storage and from any
specimen storage (if occurs onsite).
98%
122
There is evidence of mechanisms to ensure correct fill volume and quantities for each CSP.
98%
122
Compounding personnel inspect each component and supply for visible particulate matter,
tampering, breaks in packaging and other changes which would render the item unaccept­
able for use in sterile compounding.
98%
122
Labels are checked for correct names, amounts and/or concentrations of ingredients, total
volume; BUD; route of administration; storage conditions and other appropriate usage infor­
mation before they are dispensed.
98%
122
There are procedures in place for patients and caregivers to use to report questions or con­
cerns relative to CSPs they receive from the compounding location.
98%
122
The temperature of the incubator/s conforms to required temperatures for both Tryptic Soy
Agar (TSA) and Malt Extract Agar (MEA) or other suitable fungal media. Note: This item
applies regardless of risk level.
98%
104
Employees are not eligible for hazardous drug training or completion of the hazardous drug
competency until they have successfully completed the three base competencies: Hand
washing and Garbing, Cleaning and Disinfecting and Aseptic Processing.
98%
95
Certification of primary (LAFW, CAI, BSC, CACI) and secondary (buffer and ante areas) engi­
neering controls which includes particle testing is performed every 6 months; whenever a
primary engineering control is moved or subsequent to room repair or major service.
98%
122
Compounding personnel who fail written exams or media­fill tests are immediately rein­
structed and reevaluated by expert compounding personnel to ensure correction of aseptic
processes as well as demonstrate the ability to pass repeated written and/or media­fill tests.
98%
122
Compounding personnel are said to have successfully passed their media fill qualification
only if all media fill units are free from turbidity (cloudiness) after all 14 days of incubation at
the appropriate temperature.
98%
122
Compounding personnel are vigilant to prevent touch contamination and if contamination is
suspected, they discard the component, supply or preparation.
98%
122
M AY/J U N E 2 0 1 2
Table 2
10
www.nhia.org/CE_Infusion
Continuing Education
Table 2 (continued)
Highest Scoring Items that Apply to Majority of Alternate­site Providers
Compliance
Sample*
Compounding personnel perform manipulations in the direct compounding area inside of the 98%
ISO Class 5 environment in such a way as not to disrupt the flow of first air (HEPA filtered air
stream) over critical sites.
122
CSPs with observed defects are segregated from CSPs ready for use in a manner that pre­
vents their administration.
98%
122
Particle testing is performed by qualified operators using certified equipment (which can be
verified by selecting vendors who provide evidence of operator training and competency
assessment as well as equipment calibration and certification procedures).
98%
122
The methods used to transport CSPs to the patient prevent damage and maintain appropri­
ate temperatures during transit.
98%
122
*Some questions apply to a subset of the entire population due to non­scored gating questions that determined
applicability of questions based on answers to questions about type of compounding done at location.
Table 3
Lowest Scoring Items that Apply to Majority of Alternate­site Providers
Compliance
Sampl
e
There is written confirmation (example below) by each compounding employee of reproductive
age (male or female) that they understand the risk of handling hazardous CSPs.
34%
95
If your compounding location were to use a filter in compounding, is it the policy to routinely fol­
low with a filter integrity test (bubble point test)?
39%
74
Viable air sampling is performed using two different types of media: one is a general growth medium 51%
and the other is a media that specifically supports the growth of fungus, such as malt extract agar.
122
Once primary engineering controls are placed in their desired location, smoke studies have been
conducted to verify unidirectional airflow and sweeping action over and away from the critical
compounding area.
52%
112
All compounding personnel (including supervising pharmacists) successfully complete at least 3
gloved fingertip/thumb sampling procedures (success is 0 CFUs) all of which are documented
before initially being allowed to compound CSPs.
52%
122
The sink in the ante­area is equipped with hands­free controls for water and soap dispensing.
53%
107
There is evidence that mechanisms exist to report excursions, repair defects and document actions 54%
taken as a result of any out of limit pressure/airflow condition until resolution.
122
Documentation indicates that pressures (or airflow velocities if a displacement airflow design with­
out walls is employed) are monitored at least once daily.
55%
105
A line of demarcation in the ante­area or segregated compounding area separates the dirty area
from the clean area.
58%
122
M AY/J U N E 2 0 1 2
*Some questions apply to a subset of the entire population due to non­scored gating questions that determined
applicability of questions based on answers to questions about type of compounding done at location.
11