Infection Prevention in the
Hospital Compounding
Pharmacy – Best Practices
Infection Prevention in the Hospital
Compounding Pharmacy
–
Best
Practices
Presented by:
Keith H. St. John, MT(ASCP), MS, CIC
Director, Clinical Epidemiology
Sentri7 – Wolters Kluwer Health
Member, USP Expert Compounding Committee
Disclosures
Although I am a current member of the USP Compounding
Expert Committee, I am speaking today as an Infection
Preventionist and not as a member of the Committee or
as a USP representative.
I am currently the Director of Clinical Epidemiology for
Pharmacy OneSource, a Division of Wolters Kluwer
Health, serving as a consultant for Sentri7™
surveillance software solutions.
No Conflicts of Interest
Learning Objectives
 Describe the infection control issues
paramount in the sterile compounding
pharmacy
 Review the current USP <797> standards for
cleaning, disinfection, personnel cleansing
and garbing, and environmental microbial
sampling relevant to the IP
 Describe how the IP and Pharmacist can
partner as champions for medication safety
“ The very first requirement in [healthcare] is
that it should do the sick no harm.”
Florence Nightingale (1820-1910)
When is the last time you visited your pharmacy for
IC/EOC Rounds?
“It is time to step away from the computer and make
rounds in the Pharmacy, comrades!”
Real Life in the Hospital Pharmacy…..
 The following pictures were not staged and were actual conditions
found during Pharmacy rounds in a hospital somewhere in the USA.
(Photos, courtesy of Eric Kastango, RPh, MBA)
Infection Control Requirements
USP Chapter <797>
Cleaning and Disinfection
 Chapter requirements based on USP Infection Control
Expert Panel* recommendations
 Goal: Reduce bio-burden in compounding areas
 Use of a disinfectant chemical agent is required
 Cleaning should proceed from buffer area (clean room)
to ante area
 Use dedicated cleaning equipment and recommended
cleaning/disinfectant agents for floors, other
environmental surfaces
 Floors, counters, work surfaces – at least daily
 Walls, ceilings, shelving – at least monthly
* ICEP-ES Members: Keith St. John, Chair; William Rutala (SHEA), Arjun Srinivasan (CDC), Alice Weissfeld (ASM), Kathy
Gura (ASHP – hospital-based Pharmacist), Judene Bartley (APIC)
Disinfectant Chart
1
Lipophilic Viruses
Hydrophilic Viruses
M.tuberculosis
Mycotic agents
Bacterial Spores
Shelf life >1 week
Corrosive or deleterious effects
Residue
Inactivated by organic matter
Skin irritant
Eye irritant
Respiratory irritant
Toxic
Easily obtainable
Approx cost
Bacteria
Table. Common disinfectants used in health care and their microbicidal activity, properties and cost
2
Inactivation
Important Characteristics
Isopropyl
alcohol
60-95%
Low
+
+
±
+
+
-
+
±
-
+
±
+
-
+
+
Accelerated
0.5%
Low
+
+
+
+
+
-
+
-
±
±
-
-
-
-
+
0.4-1.6%
aq
0.4-1.6%
aq
1005000
ppm
30-50
ppm
>2%
Low
+
+
±
±
+
-
+
-
+
+
+
+
-
+
Low
+
+
±
+
+
-
+
-
+
±
+
+
-
+
+
+
+
+
+
+
±
-
+
+
+
Low
+
+
±
±
±
-
+
±
+
+
±
HLD
+
+
+
+
+
+
+
-
+
-
+
Germicide
Hydrogen
peroxide
Quaternary
Ammonium
Phenolics
Chlorine
Iodophors
Glutaralde
hyde
1
Use
Dilution
Level of
Disinfection
Low/HLD
2
Purchase
At use
dilution
$4.20
(70%)
$28.00
(0.5%)
$4.20
(70%)
$28.00
(0.5%)
+
$28.00
$0.11
+
+
$15.00
$0.12
+
+
+
$1.24
(5.25%)
$0.12
(0.5)
+
-
+
+
$16.00
$16.00
+
+
+
+
$10.00
$10.00
Modified from World Health Organization, Laboratory Biosafety Manual 1983; and Rutala WA. 1995. Antisepsis, disinfection and sterilization in
the hospital and related institutions. In Balows A, Manual of Clinical Microbiology, ASM, Washington DC. 227-245. Abbreviations and symbols:
ow, low-level disinfectant used on noncritical surfaces or noncritical devices/equipment; HLD, high level disinfectant; +, yes; -, no; ±, variable
results.
2
Inactivation of the most common microorganisms (i.e., bacteria) occurs with a contact time of >1 minute; inactivation of spores requires longer
contact times (e.g., 5-10 minutes for 5,000 ppm against C. difficile spores [Perez J, 2005 AJIC]) to several hours.
A Word of Caution Regarding Alcohol….The Pharmacy
take heed!
 Alcohols are not good cleaning agents, and are classified as low level
disinfectants
 Alcohols are not sporicidal (e.g., mold spores, bacillus spores)
 Alcohol’s effectiveness as a disinfectant (or a hand hygiene
antiseptic) is based upon allowing it to dry completely on surfaces
USP <797> Cleaning/Disinfection
Daily Cleaning/Disinfection:
 ISO Class 5 surfaces
 ISO Class 5 equipment
 Work surfaces near the ISO Class 5 area such as carts
 Floors
o Cleanroom
o Anteroom
o Must occur when compounding is NOT taking place
 Shipping containers
USP <797> Cleaning/Disinfection
Weekly in cleanroom:
 Storage shelving
o Empty bins of all supplies
o Clean bins
Monthly in anteroom:
 Storage shelving
o Empty bins of all supplies
o Clean bins
Compounding Personnel
 A human person in a cleanroom is
considered a broad spectrum particle
generator enclosed by inefficient
mechanical filters which may also be sources
of particles
 The human body harbors an average of 150200 different classes of bacteria
 Hands have an average of 100,000 organisms
/ sq mm
1954, Charles Schultz
Copyright, United Feature Syndicate, Inc.
 The body sheds 5 grams of skin fragments
each day along with shedding 1 layer of skin
every 5 days (size range 10 to 300 micron)
[micron = 1000th of a mm]
Compounding Personnel - PPE
 Hair net
 Beard cover and face
mask
 Gown
 Non-sterile (or sterile)
 Gloves
 Sterile
 Shoe covers
Hand Hygiene is Paramount in Preventing Contaminated
CSPs….is your Pharmacy personnel compliant?
Definitions
 Hand hygiene
o Applies to handwashing, antiseptic handwash,
alcohol-based handrub, surgical hand hygiene/antisepsis
 Handwashing
o Refers to washing hands with plain soap and water
 Antiseptic handwash
o Refers to washing hands with water and soap or other
detergents containing an antiseptic chemical agent
 Alcohol-based handrub
o Refers to rubbing hands with an alcohol-containing
preparation
 Surgical hand hygiene/antisepsis
o Refers to handwash or use of an alcohol-based hand rub,
often having persistent antimicrobial activity.
Guideline for Hand Hygiene in Health-care Settings. MMWR 2002; vol. 51, no. RR-16.
Hand Hygiene – A multi-step process
Hand Hygiene Education – A new Pharmacy School and
State Licensing Practicum Mandate?
Hand Hygiene & Garbing of PPE – Critical IC Procedures
 After donning dedicated shoes or shoe covers, head/facial hair
covering, and face mask, clean under finger nails with a nail cleaner
under running water.
 Initial hand wash is for at least 30 seconds with either plain soap or
antimicrobial soap and water, up to the elbows while in the antearea. Scrub brushes are not recommended. Dry hands and forearms
with lint-free disposable towels (preferred) or electronic hand dryer.
 Don a clean or sterile non-shedding gown closed at the wrists and
enclosed at the neck.
 Prior to donning sterile gloves in the clean (buffer) area, apply an
FDA approved alcohol-based surgical hand scrub with persistent
antimicrobial activity for the recommended amount of time (per
manufacturer) and allow to dry. (Some examples include: Avagard®,
Sterillium Rub®, Triseptin®.)
Electronic Compliance Monitoring for Hand Hygiene –
possible application for the Pharmacy Clean Room?
Hand Hygiene Compliance Monitoring Article – the State
of the Science
Environmental Sampling – Why Is It Important?
Facilitate the detection of contamination and its source:
o Sources
•
•
•
•
•
Personnel
Work surfaces
Supplies
Equipment
Failure of engineering controls
Environmental Sampling
Environmental Sampling section has been separated into a
facility-related performance metric and a personnel –
related performance metric
 Facility-related Environmental Sampling
 Viable air sampling via volumetric method (impaction) to occur at least
every 6 months, in conjunction with hood certification
 Personnel-related Environmental Sampling
 Personnel fingertip sampling during initial training, with media fills and
as a competency assessment tool
 Surface sampling for viable microorganisms in conjunction with
cleaning and disinfection quality assurance measurements
Environmental Sampling
 Designed to demonstrate that the primary
and secondary engineering controls,
disinfecting procedures, and work
practices result in a suitable environment
for aseptic compounding
 Utilizes several approaches to assess and
evaluate:




Total particle counts
Air viable organism cfu
Surface viable organism cfu
Finger touch plates
Environmental sampling conditions:
 As part of the commissioning and certification of
new facilities and equipment.
 Following any servicing of facilities and
equipment.
 As part of the re-certification of facilities and
equipment (i.e., every 6 months).
Environmental sampling conditions:
 In response to identified problems with end
products or staff technique
 In response to issues with CSPs, observed
compounding personnel work practices, or
patient-related infections (where the CSP is
being considered as a potential source of the
infection.)
Growth Media
 Soybean Casein Digest Media (Trypticase Soy Broth/Agar)
to support the growth of bacteria.
 Malt Extract Agar or other media that supports the
growth of fungi.
 Added neutralizing agents such as lecithin and
polysorbate 80 when appropriate.
o Surface sampling
o Personnel glove sampling
Sampling for Air Viable Organisms
 Volumetric air sampling is required.
 Settling Plates cannot be sole method of evaluating
air viable organisms.
o They are not qualitative
o Settling of particles by gravity influenced by size of particle
and by air movement
Courtesy of MSI, Inc. Houston, TX (www.microbiologyspecialists.com)
Viable Air Sampling
 Sampling plan to include:
o Method of collection (e.g., Impaction sampling)
o Frequency of testing
o Volume of air sampled (400-1000L)
o Time of day and activity of compounding
o CFUs action levels
 Minimum frequency of testing
o Initial facility commissioning
o At least every six months during recertification of facility and
engineering controls of all sterile compounding areas
Reference: USP <1116>: Microbiological Evaluation of Clean Rooms and Other Controlled
Environments
Volumetric Air Sampling
 Shall be performed at locations that are prone to
contamination during compounding or staging of
supplies, labeling, gowning and cleaning.
 Required frequency
o Low, medium and high-risk level compounding – at least semiannually
 More frequent sampling will provide earlier detection of
loss of environmental control.
 Base frequency of sampling on:
– Criticality of compounding occurring in area.
– Number of excursions over assigned action level.
Volumetric Air Sampling Equipment
Biotest RCS
Merck MAS100
Biotest RCS Isolator
BioScience SAS180
Surface Sampling
 Surface Cleaning and Disinfection Sampling and
Assessment
o Surface sampling is an important component of the maintenance
of a suitable microbially controlled environment
• Transfer of microbial contamination from improperly
disinfected work surfaces via inadvertent touch contact by
compounding personnel can be a potential source of
contamination of CSPs
o It is useful for evaluating facility and work surface cleaning and
disinfecting procedures and employee competency in work
practices such as disinfection of component/vial surface
cleaning.
Surface Sampling
• Contact Plates (plate size 24-30 cm2)
o Media plate which has a convex surface.
o A general growth medium such as Trypticase Soy Agar along
with neutralizing agents such as lecithin and polysorbate 80 is
usually used.
o Used to sample only smooth, flat, and nonporous surfaces.
• How to use
o Gently roll the plate over the surface to be sampled.
o Media residue will be left behind.
o Clean and disinfect sampled area thoroughly.
Surface Sampling
 Often done at the end of the shift or end of the work
day.
 Can be performed in all ISO classified areas.
 Performed using contact plates or swabs.
 Sampling areas should be defined in the sampling plan
Gloved Fingertip Sampling
 Initial training assessment with audit tool
 Successful gloving with three-time fingertip sampling
with ZERO CFUs
 Annually re-assessment for low and medium-risk
compounding operations
 Semi-annual re-assessment for high-risk compounding
operations
 During any media fills
Gloved Fingertip Sampling
Microbiological Action Sampling Levels
Classification
Volumetric
Air Sample
Required*
Finger Tip
Sample
Zero
x3
>3
Surface
Sample
ISO Class 5
>1
>3
ISO Class 7
> 10
>5
ISO Class 8
> 100
> 100
CFUs per cubic meter of air or per plate.
*A sufficient volume of air (400-1,000 L) should be sampled to
detect excursions specified in the levels above.
Environmental Sampling – Minimum Frequency Summary
 Total particles counts
o Initial facility commissioning
o At least every six months during recertification of facility and
engineering controls of all sterile compounding areas
 Volumetric Air Sampling-every six months
 Glove fingertip sampling occurs annually for Low and Medium
Risk and semi-annually for High Risk Level to assess staff
competency of maintaining aseptic practices
 Surface sampling used to evaluate the effectiveness of
cleaning/disinfecting procedures and work practices and
occurs annually for Low and Medium Risk and semi-annually
for High Risk Level sterile compounding
Environmental Sampling
 “Regardless of the number of
CFU identified in the
pharmacy, further corrective
actions will be dictated by
the identification of microorganisms recovered (at
least the genus level) by an
appropriate credentialed
laboratory of any microbial
bioburden…”
USP Chapter <797> USP 34-NF 29
Environmental Sampling
 When action levels are exceeded, an investigation into
the source of the contamination shall be conducted and
operations suspended pending the investigation.
 Sources to check:
o HVAC systems
o Damaged HEPA filters
o Changes in personnel garbing habits
o Changes in work practices
ATP sampling Technology – Supplemental EM for the Pharmacy Clean
Room?
The measurement of organic ATP on surfaces using a luciferase assay
and luminometer has been used to evaluate cleanliness of food
preparation surfaces for more than thirty years. A specialized swab
is used to sample a standardized surface area which is then analyzed
using a portable handheld luminometer. The total amount of ATP,
both microbial and non-microbial, is quantified and expressed as
relative light units (RLU).
ATP Sampling - Pharmacy
 Although readout scales vary more than 10 fold and sensitivity varies
between commercially available systems, very low readings are
typically associated with low aerobic colony counts (ACCs).
 Very high readings may represent either a viable bioburden, organic
debris including dead bacteria or a combination of both.
 Because a large proportion of surface contamination with ATP is nonmicrobial in origin, surfaces that are effectively disinfected but less
effectively cleaned may be more likely flagged as failing to meet a
quality standard for cleanliness using the ATP tool than one of the
culture techniques currently recommended for environmental
sampling.
ATP Sampling - Pharmacy
 High concentrations of bleach may potentially quench the ATP
bioluminescence reaction and result in a signal reduction, but
further research is needed to better understand the impact of bleach
based disinfectants on the use of the ATP system.
 If a bleach-based disinfectant is used, it is important that the
surface is dry before using the ATP tool.
 The ATP tool is likely to require pre-cleaning levels of contamination
for each object evaluated in order to accurately assess cleaning
practice.
The Use of Checklists to Monitor Performance
Numerous studies have demonstrated that
the use of process “checklists” for
repetitive procedures/tasks is a valuable
tool to ensure a high level of performance
and reduction of human error.
USP <797> Checklists – an IP + Pharmacist +
Environmental Services Worker partnership
 In the current USP chapter, the appendices
include examples of checklists designed to
monitor processes in the sterile compounding
environment.
 The use of checklists builds in accountability and
drives improvement in processes.
 Electronic documentation tools are available
commercially to assist in monitoring compliance.
Sample Checklist Tool
Proposed Environmental Monitoring Plan for Hospital
Pharmacies* - the IP Perspective
1. The program should be an infection preventionist/hospital epidemiologist
infection prevention & control (IPC) based program internally coordinated
and maintained through Pharmacy management level participation. The goal
should be seen as a joint (IPC/Pharmacy) team effort during planning
implementation and ongoing follow-up phases.
2. Each program should be hospital-specific and based on a joint
(IPC/Pharmacy) definition of institutional expectations consistent with the
USP and CDC standards utilizing a check list. The responsibilities of the
Environmental Services staff and other hospital pharmacy personnel for
cleaning & disinfection of all required surfaces shall be clearly defined.
3. Either covertly or in conjunction with ES staff, an objective assessment of
the terminal room thoroughness of surface disinfection cleaning should be
done using one or more of the sampling methods to document the preintervention thoroughness of disinfection cleaning (generally referred to as
the “TDC Score.”)
Proposed Environmental Monitoring Plan for Hospital
Pharmacies* - the IP Perspective
4. TDC Score is calculated as # of objects cleaned / total # of objects
evaluated X 100). Such results should be maintained by the
institution and used internally to optimize programmatic and
educational interventions.
5. Structured education of the ES staff to define programmatic and
institutional expectations should be carried out and the proportion
of staff who participate should be monitored. It would be expected
that the results of the pre-intervention objective evaluation of
disinfection cleaning be incorporated into the educational activity
in a non-punitive manner.
6. Scheduled ongoing monitoring of the TDC cleaning using one or more
of the objective monitoring approaches should be performed at least
three times a year. The monitoring should use a projected sample
size based on the previous level of TDC in order to detect a 10-20%
change in performance.
Proposed Environmental Monitoring Plan for Hospital
Pharmacies* - the IP Perspective
7.
The results of the objective monitoring program and the objectively
developed TDC scores should be used in ongoing educational activity and
feedback to the staff following each cycle of evaluation. It is recommended
that such results be shared more widely within and beyond the institution
as useful and appropriate.
8.
Results of the objective monitoring program and interventions to optimize
the thoroughness of terminal room cleaning and disinfection should be a
standing agenda item (along with hand hygiene and PPE compliance
monitoring) for the hospital Infection Prevention & Control Committee
(IPCC).
9. Results should be reported to the IPCC and facility leadership and could be
reported to the state health department through the state prevention
collaborative coordinator by various mechanisms (e.g., NHSN template),
depending on infrastructure.
*Proposed Plan is based upon the CDC Options for Environmental Cleaning document, Level II Plan, published December 2010.
Case Study
Bacterial Contamination of an Automated Pharmacy Robot Used for
Intravenous Medication Preparation
David Cluck, PharmD; Marty Glasgo, BSPharm; John C. Williamson, PharmD; Daniel Diekema, MD¹;
Robert Sherertz, MD;
Multiple cultures were positive for Bacillus cereus during routine quality
assurance testing of a pharmacy robot that prepares intravenous
medications. An investigation confirmed bacterial contamination of the
robot as well as drug product (lidocaine) made by the robot.
Infect Control Hosp Epidemiol 2012;33(5):517-520
* Affiliations: Wake Forest Baptist Health, Winston-Salem, North Carolina; ¹Departments of Internal Medicine and
Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
Case Study
Washing station and alcohol wick.
Case Study
Overhead view of washing station.
Case Study - Conclusions
The authors believed that the washing station of the Intellifill i.v.® was
the source of B. cereus contamination. It was the only culture-positive
site, and the PFGE results implicate this site, as evidenced by
a pattern matching those found in TSB and drug product.
That being said, we may never know how the organism was
first introduced into the sterile environment of the robot.
There is risk of contamination from human hands associated
with cleaning and setup. Objects are routinely exchanged
within the compartment, such as tubing, drug vials, and intravenous
fluid bags.
Although the contents are sterile, the outside of drug vials and fluid
bags are not sterile.
Case Study Conclusions
To prevent other users of Intellifill i.v. from experiencing the same
problem, the manufacturer should consider establishing a formal
procedure for cleaning and maintaining the washing station, with
more detailed recommendations to change the drain tube, the
container, and possibly the washing station itself.
In addition, it is reasonable to expand existing quality assurance
recommendations to include surface testing of the washing station
and air sampling in the center of the compartment. Lastly, using the
robot in the pharmacy’s clean room could further decrease the risk
of contamination.
In Summary….
 Any problem issues/questions that surface while performing routine
compliance monitoring and environmental sampling must be
communicated to the Infection Preventionist as soon as possible.
 Engaging the IP in problem resolution/investigation will accelerate
access to additional resources, if needed. Also the IP has
established relationships with the state/local Department of Health
if the situation escalates to that level. The State Board of Pharmacy
should also be notified when it reaches this level of concern.
 The sterile compounding area will never be sterile, so it imperative
that a state of control be maintained at all times – engineering
controls, processes, and personnel.
 Accountability is key to any infection prevention efforts!
Questions??
Keith H. St. John, MT(ASCP), MS, CIC
Email: keith.stjohn@sentri7.com
Cell: (302) 932-2753