Effective Strategies for
Designing, Building, and Maintaining a
USP <797> / USP <800>
Compliant Sterile Compounding Facility
34th Annual CASHE Seminar
September 2016
Presented by
Leach Wallace Associates, Inc. &
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Why USP <797><800>?
• Prevent harm to patients resulting from microbial bioburden,
excessive bacterial endotoxins, content error, incorrect
ingredients, or contamination of compounded sterile products
• Protect operators and environment from Hazardous Drugs
• Earlier efforts were disappointing since USP 1206 was
voluntary and initial USP <797> & <800> versions were
confusing and not comprehensive
• Risk Management due to lack of QC/Quarantine
• Roadmap for achieving documented a state of control
over pharmacy
2
New England Compounding
Center (NECC) 2012
• Fungal meningitis outbreak from contaminated
drugs, produced with expired ingredients under
unsterile conditions
• Tied to the deaths of 64 people and to illnesses in
over 700 patients in 20 states.
• NECC- shipped materials to 7 facilities in MD
infecting 26 people and killing 3.
• 14 people charged
• Co-owner/head pharmacist, and its supervisory
pharmacist, charged with 25 acts of second-degree
murder in seven states, plus additional crimes
NECC FDA 483 Findings
• Company shut off air conditioning at night
• Bacteria and mold found in cleanrooms that
exceed action limits
• No identifications of bacteria/mold
• No corrective actions or product impact
investigations
• Certain controlled areas were visibly soiled
with damaged pass through gaskets
USP <797> History
Sterile Compounding Standards
• 1992 First Standard proposed in PF18(2) April 1992
• 1996 Revised in USP23-NF18 5th supplement
General Chapter <797>
• 2003 First Published in USP27-NF22
• 2004 1st version released
• 2007 Revision Released
• Official June 2008
• Next revision out for public comment September 2015
• Next steps include release of revised USP<797> with substantial
changes
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USP <797> Major Changes
• Removal of references to Hazardous Drugs
• Defined Temperature & Relative Humidity Requirements
– 20°C (68°F) or cooler
– < 60% RH
• No in-room humidifiers or de-humidifiers
• Defined interval for Environmental Monitoring- Monthly
6
USP<800> History
General Chapter <800> History• Part of USP<797> 2004, 2008
• March 2014- 1st revision published for comment
• October 2015- 2nd revision published for comment
• February 1, 2016 Official- grace period current expected date for
compliance- July 1, 2018
• Each State Board of Pharmacy will determine effective date-TBD
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Enforcement
• Recognized as the national standard of practice
• Enforceable by the FDA and 28 State Boards of Pharmacy and
counting
• Board undergoing training for inspectors
• Inspectors will want to see how the “system” addresses
excursions and adverse events-now in COMAR for MD
• Virginia Board of Pharmacy Guidance Document: 110-36
• National Association of Boards of Pharmacy (NABP) taking
active role in supporting guideline enforcement
• JCAHO
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Overall Regulatory Trends
• Expectation of Facility Improvements
• Documented State of Control verified by data
• Boards of Pharmacy want self reporting of
adverse events
• Regulators expecting compliance–
Pharmacies tasked with
creation/maintenance of Quality Program to
maintain compliance (FDA like mentality).
• USP chapters on compounding are federally
recognized as the standard of practice in the
U.S. - full stop
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USP<797>/<800> Compliance Model
Procedures
Documentation
Facility Design
CONTROL
Personnel
Practices
Environmental
and Personnel
Testing
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Facility Requirements-Design
•
•
•
•
•
•
•
Temperature and humidity
Positive pressure
Negative pressure (Hazardous Drugs)
Air changes
Cleanable surfaces
Sealed wall and ceiling junctures
Appropriate equipment and essential activities only
Facility Requirements-Air
• ISO Guidelines for clean areas
must be met
• ISO Class 5 Laminar Flow
Hoods or BSCs
• ISO Class 7 for Buffer
Area/Cleanroom
• ISO Class 8 for Anteroom (nonchemo)
• Viable limits specified
Facility Requirements-Equipment
• Hood and HEPA Filter
Certification at 6 month
interval
• Calibration
• SOPs
• Documentation
Cleaning
• Specifies procedures for routine
cleaning, decontamination, deactivation
and disinfection of the room(s) and
Containment-Primary Engineering
Controls (C-PEC)/Hoods.
• Details location of dedicated cleaning
equipment- no mop sinks!
• Must be considered when selecting floor
and millwork finishes
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Environmental Quality & Control
• Air Quality
– Viable
– Non-viable
• Differential Pressure
• Surface Testing
• Temperature and Humidity
• Action and Alert limits
USP <797>
Challenges/Considerations
• Square footage requirements and thorough analysis
of personnel and material workflows critical in
design/re-design process
• Renovation vs. New Construction
• Dedicated Exhaust and/or Air Handling
• Back Up Power
• Temp/RH
• Detailed understanding/completion of SOPs prior to
facility completion- cleaning, EM
• Commissioning/As-Built verification
• Facility Change Control
16
USP <800> Hazardous Drugs in
Healthcare Settings
• Comprehensive approach
• Harmonization with 797 (sterile)
and 795 (non-sterile)
• To protect the patient, healthcare
professional and environment
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USP <800> Facility Design
•
•
•
•
•
Restricted access
Unpacking
Storage
Spills
Non sterile and sterile
compounding
• No Positive Pressure
Areas for Hazardous Drugs
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USP <800> Facility Requirements
• Compounding areas away from breakrooms,
refreshment areas, staff, patients, or visitors.
• SEPARATE designated areas shall be available for:
–
–
–
–
Unpacking HDs*
Non sterile HD Compounding
Sterile HD Compounding
Storing HDs (unless buffer area is used)
*Designated HD handling areas shall be segregated from non-HD areas. Unpacking
HDs from external shipping containers shall NOT occur in an area used for sterile
compounding. HDs shall not be stored, unpacked, compounded or otherwise
manipulated in an area that is positive pressure relative to the surrounding areas.
No LFH or CAIs can be used.
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USP <800> Storage
• Storage (unpacking) room must be
negative pressure, 12 ACH, and
vented outside.
• Cannot store on floors.
• HDs stored in manner to prevent
breakage or spillage
• Substantial challenge for most
pharmacy floor plans.
• Specified PPE
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USP <800> Facility Design
Three options for sterile HD compounding
1.
2.
3.
Containment secondary engineering control (C-SEC): ISO Class 7 or
better room that serves as a buffer/cleanroom, and ISO Class 7
Anteroom. Negative pressure required to provide containment.
Anteroom is positive pressure to maintain cleanliness. All rooms
minimum of 30 Air Changes Per Hour AND VENTED OUTSIDE.
Containment segregated compounding area (C-SCA). Limited for use
with a BSC (VENTED OUTSIDE) when preparing low or medium risk
level CSPs with 12 hour or less BUDs. Negative pressure to provide
containment. Minimum, 12 Air Changes Per Hour AND VENTED
OUTSIDE.
Containment segregated compounding area (C-SCA). When using
validated CACI (VENTED OUTSIDE), BUD based on risk level.
Negative pressure to provide containment. Minimum, 12 Air Changes
Per Hour, AND VENTED OUTSIDE.
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Hazard Communication Program
• Required by OSHA
• Employers required to establish
policies and procedures to ensure
worker safety in all aspects of
distribution of drugs as part of OSHA
Hazardous Communication Standard
(HCS)
• Specifies PPE for each activity
associated with receiving, handling,
stocking, compounding, administering,
clean up, and spill remediation.
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Cleaning
• Specifies procedures for routine
cleaning, decontamination, deactivation
and disinfection of the room(s) and
Containment-Primary Engineering
Controls (C-PEC).
• References Cleaning Section of USP
<797>
• Specifies PPE
• Must be considered when selecting floor
and millwork finishes
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USP <800>
Challenges/Considerations
• Square footage requirements and thorough analysis of personnel and
material workflows critical in design/re-design process
• Renovation vs. new construction
• Dedicated Exhaust and/or Air Handling
• Temp/RH
• Segregated Storage in its own room
• External venting- hoods/rooms
• Differential Pressure requirements
• Detailed understanding/completion of SOPs prior to facility completioncleaning, EM
• Commissioning/As-Built verification
• Facility Change Control
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CSP Considerations
• Usually consist of an area within the pharmacy but
separated by walls and hard ceilings with clean and dirty
areas and a clean ante room
• Direct Compounding Area (DCA) is the actual
compounding work surface
– Usually inside a hood in a clean air buffer area
• Mixing of sterile products are prepared in an ISO Class 5
or better environment
• Products have a shelf life of 30-48 hours
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General Pharmacy Design
Criteria
•
•
•
•
•
4 ACH
2 OA
Positive pressurization
Temperature 70°-75°F
RH < 60%
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Architectural Considerations
• Seamless Flooring
• Drywall Ceilings
– Eliminate or minimize access panels
– Place dampers, junction boxes out of room
– Provide remote HEPA module fan speed switches below ceiling
• Door Sweeps/Seals
• Pass-Throughs (Sealed)
• Sink Locations
• Eyewash Locations
• Powered Door Operators
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Example Pharmacy
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Environmental Design
Requirements
• Sterile Compounding Rooms
– Temperature: 68°F
• Continuous Visual Monitoring/ Trending Required
– Humidity: Maximum 60%
• No minimum humidity level indicated
Room
Pressure Relationship
Additional Requirements
Chemo Clean
Room
Negative (-0.02” W.G.) to Ante Room
ISO 7 Ante Room
Admixture
Room
Positive (+0.02” W.G.) to Ante Room
ISO 8 Ante Room unless shared with Chemo
Clean Room
Ante Room
Positive (+0.02” W.G.) to Adjacent Corridor/
Space.
Negative to Clean Rooms.
Unpacking /
Storage
Negative (-0.02” W.G.) to Corridor/ Adjacent
Space.
USP <800>
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Room Air Change Rates and
Filtration Requirements
VELOCITY & AIR CHANGE RATES FOR SELECTED CLEAN SPACE CLASSES
Space Classification
ISO
Federal Standard 209E
Average Room
Velocity (fpm)
Air Changes
per Hour
Filtered Ceiling
Coverage
5
100
40-80
240-480
100%
7
10,000
10-15
30-60
5-40%
8
100,000
1-8
5-30
--
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Cooling Loads
• Cooling Load Calculations
– Room Envelope
• Walls
• Roof Load
– Internal Loads
• People
• Lighting Equipment
• Hood(s)
– Heat Gain from Fan-Powered HEPA Module Fans
– Consider Source
• System 24/7/365
• Typical Outpatient Facility HVAC systems operate on
occupied/unoccupied modes
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HVAC Systems: Air Handling
Systems
• Typical In-Hospital Systems
– Operate 24/7/365
– Higher Percentages of Outdoor Air
• To accommodate Chemo Hood and Unpacking Room makeup air
requirements
– Reheat Systems
• 60% Maximum humidity threshold ok with 68°F Room Temperature
• Typical Outpatient Systems
– DX (Direct Expansion)
– Designed for minimum outdoor air
– Additional features/controls are needed to maintain maximum
60% space humidity due to increased outdoor air
• Digital scroll compressor(s) for capacity control
• Hot gas reheat/ dehumidification controls
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HVAC Design Options
• ISO 7 Clean Room
– Compounding within an ISO 5/ Class 100 Clean
Room
• Room Air Change Requirements
– 30 to 60 Air Changes Per Hour
• Provide “House” airflow for cooling loads and pressurization
requirements
• Air Change Requirements provided by ceiling-mounted fanpowered HEPA modules
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Airflow Summary
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Airflow Schematic
35
AIRVELOPE Model 39
36
Compounding Airflow
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Electrical Design Requirements
• Emergency Power
–
–
–
–
–
–
HEPA Fan-Powered Filter Modules
Chemo Hood
Chemo Hood Exhaust Fan
USP <800> Room Exhaust Fan
Room Pressure Monitors
Sealed Lighting Fixtures
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Key Questions for Pharmacy
Management
• Does our facility meet requirements?
• Do our personnel and material workflows work with or
against our specific facility and engineering controls?
• Do we have a documented state of control?
• Do we identify, investigate, correct and document
adverse environmental events?
• Does the C-Suite understand the risk associated with
non-compliance?
• What is our compliance budget/resources?
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Resource Impacts on Pharmacies
• Investment in facilities to meet regs.
• Investment to ensure as-built conditions
• Investment in establishing robust Quality
System/Program based on regs., then id resources to
execute and maintain
• Investment of resources/infrastructure to respond to
adverse events and regain state of control
• Staff buy-in to create/maintain a culture of compliance
• Can small satellite/oncology practices afford
compliance?
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Questions
• Jeff Lange, Quality Solutions, LLC,
[email protected], 410-852-5267
• Bob Leach, Leach Wallace Associates, Inc.,
[email protected], 410-579-8100
• Chris McCarthy, Leach Wallace Associates, Inc.,
[email protected], 410-579-8100
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