Transcript USP : Ensuring a State of Control

USP <797>: Ensuring a State of Control
AAHP Fall Seminar 2016
Thanks to Critical Point LLC (www.criticalpoint.info) for
allowing me to use their slides:
Kate Douglas, MS, RN, CRNI
Eric Kastango, MBA, BS Pharm, FASHP
James Wagner
Learning and Performance Objectives
At the end of this session you will be able to:
• Describe documented patient harm caused by inadequate sterile
compounding operations
• List common sources of contamination of a compounded sterile
product
• Describe methods to ensure a proper state of control for sterile
compounding operations
• State commonly violations of USP <797> by the Arkansas Board of
Pharmacy
History of Sterile Compounding
• Despite the chapter’s uniform sterile
compounding standards, schools of pharmacy
may not always include sterile compounding
• Only 1 in 6 graduates are prepared for sterile
compounding work*
• In 2014, less than 10 schools of pharmacy
conducted training in real cleanroom settings
*Hellums M, Alverson SP, Monk-Tutor MR. Instruction on compounded sterile preparations at U.S.
schools of pharmacy. AJHP. Volume 64, Nov 1, 2007: 2267-74.
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DQSA
• Section 503A (21USC353a) - Traditional compounding
 State-based regulations – State Boards of Pharmacy
 Traditional, individualized prescriptions
 Requires compliance with USP chapters on compounding
• Section 503B (21USC353b) - Outsourcing facilities
 FDA jurisdiction; registration; reporting; cGMPs
 Manufacture and interstate shipment of larger quantities of compounded drugs
without prescriptions
 Under direct supervision of a pharmacist
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Patient Harm Caused by Inadequate
Compounding Operations
“Our patients have
never had a problem”
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What’s the past damage?
• U.S. Illnesses and Deaths Associated With Compounded Medications
• Contamination of sterile preparations was the most common
compounding error, though others were the result of pharmacists'
and technicians' miscalculations and mistakes in filling prescriptions.
Since 2001  over 25 pharmacy compounding incidents with
1,049 adverse events, including 89 deaths, have been reported.
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Brutal Facts
Year
1990
1990
State
Nebraska
Description
4 patients died of a bacterial infection from non-sterile cardioplegia solution
compounded in a hospital
Pennsylvania 2 patients lost their vision after becoming infected by Pseudomonas
aeruginosa found in indomethacin eye drops compounded in a drug store
even though commercial non-steroidal drops were available at the time
1998
California
11 children became septic—10 tested positive for Enterobacter cloacae
bloodstream infections associated with contaminated prefilled saline syringes
2001
Missouri
4 children contracted Enterobacter cloacae infections from IV ranitidine
compounded in a hospital pharmacy
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Brutal Facts (continued)
Year
2002
State
North Carolina,
South Carolina
2002
Michigan
2003
Missouri
2004
Description
5 patients developed Exophiala infections from contaminated injectable
methylPREDNISolone that was prepared by a compounding pharmacy;
one patient died
Pharmacy preparing injectable methylPREDNISolone and baclofen recalled
the products because of contamination with Penicillium mold,
Methylobacterium, and/or Mycobacterium chelonae
Bacteria contamination with Burkholderia cepacia found in at least 2
batches of a compounded inhalant solution used by 19,000 patients with
chronic lung diseases
Texas, New York, 36 patients developed Pseudomonas bloodstream infections after
Michigan, Missouri receiving heparin/saline flushes from multiple lots of preloaded syringes.
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Brutal Facts (continued)
Year
2005
2005
State
Description
New Jersey, Up to 25 patients contracted Serratia marcescens infections due to
California contaminated magnesium sulfate mini-bags prepared by a compounding
pharmacy
Minnesota 2 patients were blinded after receiving a compounded trypan blue ophthalmic
injection contaminated with Pseudomonas aeruginosa and Burkholderia
cepacia; the injectable product is a commercially available product
2005
California
Sterile talc vials with unwashed stoppers were not sterility tested before
distribution from an outsourcing compounding pharmacy
2005
Maryland
10 patients died after exposure to cardioplegia solution from 2 lots
contaminated with gram-negative rods
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Brutal Facts (continued)
Year
2011
State
California,
Florida,
Tennessee
Description
16 patients being treated for wet macular degeneration developed severe eye
infections due to contamination of AVASTIN (bevacizumab) during
compounding; one patient blinded, another patient developed brain infection
2011
Alabama
9 patients among 19 died when PN solutions that were administered were
contaminated with Serratia marcescens during compounding using non-sterile
components to prepare amino acids Link to: CDC/USP Webinar on Incident
2012
California
9 patients developed fungal endophthalmitis after use of the compounded
product Brilliant Blue-G (BBG) or receiving injections of triamcinolonecontaining products dispensed from the same compounding pharmacy
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New England Compounding Center (NECC) Meningitis Outbreak
Date
September 21, 2012– October 23, 2013 (no further CDC updates expected)
Location
USA (20 States)
Cause
Fungal meningitis contamination of steroid medication
Injuries
751 total case count; 384 meningitis and spinal infection; 7 stroke; 325 paraspinal/spinal
infection; 33 peripheral joint infection; 2 spinal and peripheral joint
Some patients recovering from the meningitis are falling ill again. Sufferers of the new
infection are now coping with epidural abscesses and infections near the injection site.
Death(s)
64
Litigation
More than 20 lawsuits filed against NECC
The scale of the meningitis outbreak makes this event the worst among a series of fatal or harmful
infections and overdoses linked to pharmacy compounding practices in the US rivaling other key drug
safety issues in the past that have led to substantial drug safety legislation.
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Brutal Facts Continue Since NECC 2013 & 2014
Year
2013
State
Connecticut
Description
FDA announced that a compounding pharmacy in New Jersey was voluntarily
recalling all of its products after a Connecticut hospital reported that 5 bags
of magnesium sulfate from the pharmacy were contaminated with mold. The
pharmacy has since been closed by the NJ Division of Consumer Affairs
Georgia,
A compounding pharmacy in Augusta, Georgia, is voluntarily recalling 79 lots
Louisiana,
of bevacizumab-filled syringes (Avastin, Genentech) intended for retinal
South Carolina injections because of the risk for eye infection, the US Food and Drug
and Indiana Administration (FDA) announced yesterday.
Texas
A batch of compounded IV Calcium Gluconate found to be contaminated
with Rhondococcus equii. 15 infected patients, 2 deaths (relationship to drug
not known)
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Another Recent Event
• Outbreak of Burkholderia contaminans linked to Intravenous
Fentanyl from an Institutional Compounding Pharmacy
 Occurred at Duke University Hospital from August 31-Sept 6, 2012
 7 patients affected
 Prepared drug from bulk API: High-risk compounding
 Report published in JAMA
 Available online: JAMA Intern Med. Published online February 03, 2014.
doi:10.1001/jamainternmed.2013.13768
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FDA Inspection of Compounding Pharmacies
Figures do not include pharmacies dedicated to
producing veterinary drugs. Note: years represent fiscal
years October 1 – September 30. Fiscal year 2014
includes data through 9/12. Source: US Food and Drug
Administration, USA Today Research.
Table excerpted from: Eisler P and Schmaars C. Safety,
sanitary problems prompt scores of drug recalls. USA
Today. October 7, 2014 retrieved from
http://www.usatoday.com/story/news/nation/2014/10/
07/compounding-pharmacy-recalls-inspectionscontamination/16472741/ on October 7, 2014.
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What went wrong?
• Leadership: Inadequate and ineffective
•
•
•
oversight
Education, competence and proficiency
 Untrained employees
 Lack of competency and proficiency
evaluation systems
Hand Hygiene and Garbing
Engineering controls and equipment
 Inadequate for intended activities
 Improper use
Failure of Leadership
Image courtesy http://www.guardian.co.uk/uk/2009/jan/21/1
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What went wrong? (continued)
• Inadequate cleaning/disinfecting
practices
• Inadequate preventive maintenance
• Inadequate policies and procedures
• Equipment
 Improper use of sterilizing equipment
 Failure to validate systems
• Record keeping
 Inadequate quality assurance
 Inadequate documentation
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"Unfortunately, there are too many in
health care who feel that if it hasn't
happened to them, the adverse
experiences of others do not apply. “
Michael Cohen, MS, FASHP
Institute for Safe Medication Practices (ISMP)
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What’s the past damage?
• Since 2001 over 25 pharmacy documented compounding incidents
with 1,049 adverse events, including 89 deaths, have been reported
• True
• False
Sources of Contamination
Why is garbing important?
• Humans are the biggest “particle
•
•
generators”
Though we can’t see them, we shed about
9 pounds of dead skin cells from the outer
layer of the skin each year1
Particles generated by humans, our
clothes, and our activities can act as
transport vehicles for microorganisms and
introduce them into the compounding
process
1Donovan S.
©Photo Quest Ltd/Science Photo Library/Corbis
Stay Clear!: What You Should Know about Skin Care. Health Zone. Lerner Books. September 2008.
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Just how many bacteria?
• Each of us carries 3-5 pounds of bacteria in our
•
•
bodies!
Bacteria cells outnumber human cells 10:1
Bacterial cells are much smaller than human cells
so they only account for 1-2% of our body mass
The bacteria in our body would
fill a large soup can like this one
Source: Lita Proctor, National Institutes of Health’s Human Microbiome Project
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Garbing…why?
Compounding personnel are the chief particle generators.
1Particle
Activity1
Particles Generated
Sitting quietly
100,000/minute
Walking slowly (1.9 miles/hour)
5,000,000/minute
Walking medium (3 miles/hour)
7,500,000/minute
Walking fast (5 miles/hour)
10,000,000/minute
Makeup/Cosmetics2
Particles/Application
Eye shadow
82,000,000
Typical mascara application
3,000,000,000
Total for typical makeup application
5,100,000,000
Measuring Systems. Basic Guide to Particle Counters and Counting. 2011.
K. Cosmetics in Cleanrooms…again. Cleanrooms. 2001
2Goldstein
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Why is hand hygiene important?
•
•
There are 10,000 to 10,000,000 microbes on each hand1
•
It only takes one to make a patient sick!
So even if hand hygiene is performed with an agent that is 99.99% effective (assuming your
hand washing technique is perfect), there will still be 100 to 100,000 left on your hands
Hand hygiene is the single most important factor in
preventing the spread of pathogens in healthcare settings.
1
Health Protection Agency. Fun Facts about Handwashing. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1254510461483
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Critical Factors in Aseptic Technique
•
Illnesses in Children's Hospital Prompts Discovery of Contaminated Alcohol Pads
 Science Daily (June 12, 2012): A small cluster of unusual illnesses at a
Colorado children's hospital prompted an investigation that swiftly
identified alcohol prep pads contaminated with Bacillus cereus bacteria,
according to a report in the July issue of Infection Control and Hospital
Epidemiology, the journal of the Society for Healthcare Epidemiology of
America.
 The investigation ultimately led to an international recall of the
contaminated products.
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Contamination CONTROL
If it doesn’t get into controlled environments,
then it doesn’t pose a risk!
•
•
Seasonal variation: Spring and Summer
•
Cleaning is necessary to address mistakes in contamination control
Be careful of EVERYTHING you bring into controlled environments (e.g., sharpie marker
caused fungal contamination)
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A Word about Material Handling
• 60% packaging contaminated with bacteria and
•
•
•
40% with bacterial spores*
If wipe with IPA (not a sporicidal) only 27.6% of
spores would be removed through mechanical
means*
Spraying alone not effective since bacteria and
spores can create a protective biofilm that
must be removed by wiping**
Mold is endemic to all brown cardboard and if
it gets damp mold actively grows
*Cockcroft et al. Validation of Liquid Transfer Disinfection Techniques for Transfer of Components into Hospital Pharmacy Cleanrooms. Hospital Pharmacist. 2001;8:226-32
**Stubbs S. How to Minimize Contamination When Transferring Items Into Hospital Cleanrooms. Controlled Environments. June. 2006.
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When to use Sterile Water?
• Sterile water (SWInj or SWIrrig) is
•
strongly recommended to dilute
disinfectant solution concentrates (not
ready to use) that are used inside of
the ISO Class 5 areas.
Though these areas and cleaning
Type Water
supplies are not sterile, use of sterile
water reduces pyrogens and potential Tap Water
Purified Water
bioburden.
Water for Inj.
CFU/mL*
Pyrogens*
500
100
< 10
100 EU/mL
0.25 EU/mL
< 0.25 EU/mL
*Sources: USP NF defines standards for Purified water and Water for Injection; US EPA defines
drinking water standards
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Sterility Assurance Level (SAL)
•
Aseptic processing only achieves a SAL of 10-3 versus 10-6 when terminally sterilized
Aseptically
Prepared
SAL 10-3
1 contaminated CSP
1000 CSPs
Terminally
Sterilized
SAL 10-6
1 contaminated CSP
per million CSPs
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Which of the following are SOME of the potential
sources of contamination for CSP preparation?
A. Improper hand
hygiene, clothing, and
cardboard
B. Tap water, non-sterile
alcohol, and exposed
skin
C. Non-sterile gloves,
spring, and summer
D. All of the above
Ensuring a “State of Control”
Take advantage of this free resource
Register at http://797gaptool.com
Take advantage of this free resource
Register at http://800gaptool.com
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Cleaning
Mechanical process (scrubbing)
using soap Cleaning
or detergent and water
to remove dirt, debris and many
germs. It also removes invisible
debris that interferes with
disinfection.
Sanitizing
Sanitizing
Chemical process
of reducing the
number of disease-causing germs on
cleaned surfaces to a safe level.
Definitions
Disinfecting
Chemical process that uses specific
productsDisinfecting
to destroy 100% harmful
bacteria, viruses and fungi but not
necessarily their spores on
environmental surfaces.
Sporicidal Agents
ChemicalSporicidal
process that destroys
100% of harmful microorganisms
and spores
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Factors in Selecting Agents for Cleaning
•
Cleaning is a mechanical process enhanced by germicidal detergents to remove dirt, debris,
biofilm and microbes
•
•
•
•
•
Cleaning prepares a surface to be disinfected
Most general cleaning agents have a surfactant that removes dirt
Bleach is not a cleaning agent and does not have surfactant
Alcohol is not a cleaning agent, it is a disinfectant
Many cleaning agents also work to disinfect but application of a cleaning agent that also
disinfects does NOT replace the use of sterile 70% IPA inside C-PECs!
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Cleaning Agent Classes
Hydrogen Peroxide Agents
•No residues, no rinsing, not corrosive
•Effective against yeast, fungi, bacteria, virus and spores based on concentration
•Easy to store and stable
Peroxyacetic Acid and Hydrogen Peroxide Agents
•Broad-spectrum; sporicidal at low concentrations and ambient temperatures
•Inactivates gram+, gram-, fungi, yeasts, viruses and spores
•Not inactivated by organics and enhance their removal; Byproducts: oxygen, acetic acid and water
Phenolic Agents
•Many of these also EPA-registered disinfectants on environmental surfaces
•Based on dilution are fungicidal, virucidal and bactericidal
•Unpleasant odor; leave gummy residue that requires rinsing; may damage surfaces
Quaternary Ammonium Compounds
•Never sporicidal; poor activity against mycobacterium; poor activity against hydrophilic viruses
•Must be rinsed; may be irritating to eyes
•Efficacy reduces by hard water and organic material
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Material Handling DOES MATTER!
USP Chapter <797>:
• "Supplies and equipment removed
from shipping cartons shall be wiped
with a suitable disinfecting agent (e.g.,
70% IPA) delivered from a spray bottle
or other suitable delivery method.
After the disinfectant is sprayed or
wiped on a surface to be disinfected,
the disinfectant shall be allowed to dry,
during which time the item shall not be
used for compounding purposes."
Best Practice:
• Suggest use of a sporicidal agent such
as
 PeridoxRTU®
 Bleach (5000 ppm = 0.5%)
 Other Sporicidal agents
• Instead of IPA since there have been
•
reports of mold spores in corrugated
cardboard.
IPA is also used by laboratories as a
transport vehicle for spores.
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When to perform daily cleaning?
This is excerpt from 797
but was not the
intended meaning.
• The daily cleaning (and disinfection) best occurs at the end of the day to leave the
•
room to rest clean.
Disinfection with sterile 70% IPA (sIPA) must occur to the interior surfaces of the
PEC before compounding is begun the next day (or the same day for 24 hour
pharmacies)
• Cleaning activities may not occur while compounding is taking place
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A cleanable step stool is essential….
• Some type of step stool must be
available in controlled spaces to
properly clean:
 Wall clocks
 Life Safety Signs
 Top of PECs
 Tops of doors
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Cleaning Procedures
• Clean from cleanest to dirtiest




•
•
ISO 5 PEC
Buffer area
Ante area
General supply area
Use suitable dedicated mops and
cleaners
Must use germicidal detergent
everywhere including PEC
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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
Monitors State of Control
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Why Is ES Important?
• Facilitates early detection of
contamination and its source which
may include:
 Personnel
 Work surfaces
 Supplies
 Equipment
 Failure of engineering controls
Courtesy CBS News
This is a image of the fungus growing from a
sample taken from a patient’s spinal fluid.
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Environmental Sampling (continued)
•
•
Facility Related Metrics
Non Viable Sampling
 Temperature
 Pressure/Velocity
 Particle Sampling
Personnel Related Metrics
• Surface Sampling
• Gloved Fingertip Sampling
• Media-Fill Testing
Viable Air Sampling
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Actions to Take When Action Levels Exceeded
• An investigation into the source of the
•
contamination must be conducted.
Sources:
 HVAC systems: changes externally
 Damaged HEPA filters
 Changes in personnel garbing habits
 Changes in work practices
 Failure to follow PnP
 New employees
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Environmental Sampling Plan Requirements
•
An ES program provides a way to
monitor that the equipment,
cleaning and other work practice
controls result in a compounding
facility controlled environment
that is suited for compounding
sterile preparations and detects
any drift from an ongoing state of
control.
• When sampling occurs
• Where sampling occurs
• Number/size of samples
• Under what conditions sampling
•
•
•
•
occurs
Materials required including media
types and incubation conditions
Action Levels
Documentation
Actions required in the event of
excursions
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Speciation to Genus Level Currently Required
“Regardless of the number of cfu
identified in the pharmacy, further
corrective actions will be dictated by the
identification of micro-organisms
recovered (at least the genus level) by an
appropriate credentialed laboratory of
any microbial bioburden…”
- USP Chapter <797> USP 34-NF 29
Proposed Chapter requires that when samples
exceed the action levels, genus must be identified
and if possible, the species of microorganisms must
be identified with the assistance of a credentialed
microbiology laboratory
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CFU Identification and Sources
Microorganisms
Staphylococcus/ Micrococcus
Gram negative rods
Bacillus species
Molds
Yeast
Diptheroids/ coryneforms
Indication
Personnel habits or gowning problems
Water condensation, leaking, aerosols
Dust, dirt, floor traffic, possible air handling
Influx of unfiltered air, mold from street clothing or moldcontaminated cardboard, water reservoir, i.e. incubator
humidification system
Possible outdoor air influx; clothing-borne, especially in late
summer/ fall; possible human contaminant
Poor air conditioning (leading to sweating and personnel
discharge from gowns)
Source: Microbiological Environments (www.microbioenv.com)
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What are SOME methods to ensure a state of
control?
A. PROPER selection of
cleaning, disinfection, and
sporicidal agents
B. PROPER order of cleaning,
disinfection, etc
C. PROPER staff training,
validation, and
accountability
D. PROPER environmental
monitoring and trending of this
data
E. All of the above
“Opportunities” Recommended by the ABoP
Arkansas Board of Pharmacy
• Design of sterile compounding area – Discuss proper design for non-HD and HD
rooms
• Pressure differentials between classified and non-classified rooms
• Insufficient air-exchanges in classified areas
• Lack of HEPA filter leak tests (discuss access port expectations)
• HEPA air supply expectations
• Certification company expectations
• “Clean” and “dirty” side designation for anterooms
• Volumetric/viable air sampling expectations
• Plan for corrective actions when alert levels reached/exceeded
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Arkansas Board of Pharmacy (cont.)
• Inadequate documentation of
• Temperature, pressure, and humidity
• PEC and SEC cleaning/disinfection
• Personnel training , media fill, and glove fingertip testing (initial and ongoing)
• Improper storage of chemotherapy medications
• Stored with other medications
• Not stored in a negative pressure room with at least 12 ACH (don’t make
non-HD room negative pressure)
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Environment vs. Personnel
“ The most important variable affecting
microbial contamination of admixtures
was the aseptic technique of personnel,
not the environment in which
the drugs were compounded.* ”
*Thomas M, Sanborn M, Couldry R. IV admixture contamination rates: Traditional practice site versus a class 1000 cleanroom. Am J HealthSyst Pharm. 2005; 62:2386-92
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Facility Design and Equipment
•
•
•
•
•
•
•
Classified space function and design
Primary engineering controls
Buffer area
Ante area
Air supply
 HEPA
 Pressure
Segregated compounding area
Equipment, surfaces, and supplies
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Airflow Definitions
Turbulent flow
• Dilution control to reduce particulate
levels
• Adequate HEPA filtered airflow
supplied to the cleanroom and
anteroom is required to maintain
cleanliness classification during
operational activity
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Ante-Area
Non-hazardous applications:
• Anteroom must achieve at least ISO
class 8 conditions & be positive
pressure to uncontrolled spaces 
Negative to compounding room
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Ante-Area
Hazardous applications: Anteroom must
achieve at least ISO class 7 & be positive
to uncontrolled spaces  Positive to the
HD compounding room
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Secondary Engineering Controls
•
Adequate HEPA filtered airflow supplied to the cleanroom and anteroom is required to
maintain cleanliness classification during operational activity through the number of air
changes per hour.
 Minimum of 30 HEPA filtered Air Changes Per Hour (ACPH) in Buffer Area
 No less than 15 ACPH must be provided as fresh HEPA air supplied through the room’s
HVAC system
 This assumes additional HEPA filtered air is provided to the room through the primary
engineering control.
 Supply airflow typically not continuously monitored
 Room pressure monitored
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Secondary Engineering Controls
Ventilation efficiency
•
HEPA filtered supply air is introduced at the ceiling with low-wall mounted returns, creating
a general top-down dilution of room air with HEPA filtered make-up air.
 Ceiling-mounted returns are not recommended
•
•
•
Recommend ceiling-mounted HEPA filters
HEPA filters and returns well distributed throughout the room
Return locations at least as important as supply inlet locations
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Ceiling mounted HEPA filters
Low-wall mounted returns
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Secondary Engineering Controls
• All HEPA filters should be efficiency
•
•
tested at the most penetrating
particle size
 leak tested at the factory and
 leak tested again in situ after
installation.
IEST type C or K HEPA filter
CETA guide CAG-003-2006 for field
certification
Filter leak tested and repaired
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Hazardous Drug (HD) Applications
•
Hazardous drugs shall be stored separately from other inventory in a manner to prevent
contamination and personnel exposure.
•
•
•
Minimum of 12 ACPH
•
HD Buffer rooms housing CACIs must meet the minimum 0.01” w.c. negative pressure and
12 ACPH requirements.
Negative pressure
The ISO class 5 BSC or CACI shall be placed in an ISO class 7 room that is physically
separated, e.g., a different room from other preparation areas, and optimally has no less
than 0.01 inches water column (w.c.) negative pressure to adjacent rooms.
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Pass-Through Usage/Location
• Pass-Through Position
 Classified to Classified
 Classified to Unclassified
 FDA Position
 BOP Positions
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Secondary Engineering Certification
NSF certification for BSC
CAG-003-2006: CETA Certification Guide for
Sterile Compounding Facilities
• Airflow testing
• Airflow smoke pattern test
• HEPA Filter Installation Leak Test
• Particle Count Survey
• Optional tests
 Light, sound, temperature, humidity
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Secondary Engineering Controls
Test
Non Haz Buffer
Anteroom
C-SEC
C-SCA
Airflow
≥30 ACPH (at least 15 ACPH from
outside the room) usually more
≥ 20 ACPH (from FDA guidance) but
usually more is desirable
≥ 30 ACPH
≥ 12 ACPH for C-SCA
or any area where
HDs are stored
Room
Segregation
Minimum differential pressure of 0.02” w.c. positive from buffer to
anteroom and then again from anteroom to adjacent spaces
If displacement airflow (will no longer be acceptable when Proposed USP
797 becomes official), then velocity of 40 feet/minute from cleanroom to
the anteroom across the entire opening
Minimum differential pressure of
negative 0.01 to 0.03” w.c. from CSEC/C-SCA to adjacent space
Displacement airflow not allowed in HD
compounding
HEPA Filter Leak
Test
All HEPA filters in the secondary engineering controls are tested at each certification.
Maximum allowable leakage is 0.01% of the upstream aerosol concentration.
Smoke Pattern
Testing
Buffer rooms must be segregated from the ante-area and all other adjacent spaces. Use smoke around the opening of
doors to ensure air is traveling in the correct direction.
Non-Viable
Particle Counts
ISO Class 7
ISO Class 8 unless it serves HD buffer
then ISO Class 7
ISO Class 7 in buffer room
No ISO classification required in C-SCA
Airborne particle counter used to sample particle levels in all ISO classified locations
under dynamic operating conditions.
Temperature
Comfortable, typically a temperature of 64-66°F but Proposed USP 797 requires 20°C or cooler
Humidity
Not mandatory at this time but Proposed USP 797 requires relative humidity at or below 60% at all times
Adapted from CETA Certification Matrix for Sterile Compounding Facilities CAG-003-2006-13, USP <797>, Proposed USP <797>,
and USP <800> on 3/11/2016.
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What is the best pressure gradient between a HD
room and its associated anteroom?
A. Greater than + 0.02 W.C. (with at least 12 ACPH)
B. Greater than - 0.01 W.C. (with at least 12 ACPH)
C. Between - 0.01 and - 0.03 W.C. (with at least 12 ACPH)
Thanks again to Critical Point LLC
(www.criticalpoint.info)
and especially Kate Douglas, MS, RN, CRNI