Sterile Compounding: Facility Metrics Metrics.pdf · Facility Metrics Selected Work Practices Inspector Evaluation Metrics Primary and Secondary Engineering Controls ... unidirectional

Sterile Compounding:Facility Metrics

Copyright © 2008-2014 ClinicalIQ, LLC® - All Rights ReservedCopyright © 2008-2014 ClinicalIQ, LLC® - All Rights Reserved

Sterile Compounding:Facility Metrics

Eric S. KastangoOctober 9, 2013

Important Inspector Evaluation Metrics

Facility MetricsSelected Work Practices Inspector Evaluation Metrics

Primary and Secondary EngineeringControls

• Facility Maintenance PnP• Certification Documents

• Airflows (ACPH)• Non-viable particle counts (dynamic operating

conditions)• Viable air sampling results (dynamic operating

conditions)• Segregation (pressure/velocity)• Smoke Testing (dynamic operating conditions)

• Environmental Sampling Plan• Pressure/Velocity Differential Logs• Temperature/Humidity Logs

Copyright © 2008-2014 ClinicalIQ, LLC® - All Rights Reserved

• Facility Maintenance PnP• Certification Documents

• Airflows (ACPH)• Non-viable particle counts (dynamic operating

conditions)• Viable air sampling results (dynamic operating

conditions)• Segregation (pressure/velocity)• Smoke Testing (dynamic operating conditions)

• Environmental Sampling Plan• Pressure/Velocity Differential Logs• Temperature/Humidity Logs

Cleaning and Disinfecting onControlled Sterile CompoundingEnvironments

• Written Policy and Procedure• Employee Training• Written Competency Verification• Cleaning Logs

Polling Question

A LAFW (laminar airflow workbench) is an example ofa secondary engineering control?

1. True2. False


Kate

Highlight

What are Primary Engineering Controls (PECs)?

• There are 5 types of PECs designed to eliminate particles throughdelivery of unidirectional HEPA filtered air to the directcompounding area (DCA):

– Laminar Airflow Workbench (LAFW)

– Vertical Cleanbench (VCB)

– Compounding Aseptic Isolator (CAI)

– Biological Safety Cabinet (BSC)

– Compounding Aseptic Containment Isolator (CACI)


• There are 5 types of PECs designed to eliminate particles throughdelivery of unidirectional HEPA filtered air to the directcompounding area (DCA):

– Laminar Airflow Workbench (LAFW)

– Vertical Cleanbench (VCB)

– Compounding Aseptic Isolator (CAI)

– Biological Safety Cabinet (BSC)

– Compounding Aseptic Containment Isolator (CACI)

What are Secondary Engineering Controls?

• Secondary Engineering Controlsare designed to reduce particlesthrough the delivery of HEPAfiltered air to the room tofacilitate the operation of theprimary engineering controls.

• The Buffer Area commonlyreferred to as a cleanroom– This room is where the PECs are

placed– <797> requires it to attain ISO

Class 7 air cleanliness or better


• Secondary Engineering Controlsare designed to reduce particlesthrough the delivery of HEPAfiltered air to the room tofacilitate the operation of theprimary engineering controls.

• The Buffer Area commonlyreferred to as a cleanroom– This room is where the PECs are

placed– <797> requires it to attain ISO

Class 7 air cleanliness or better

What are Secondary Engineering Controls?

• The Ante-area (anteroom) is theroom directly outside the bufferarea– This room is to perform hand

hygiene, garbing and stagecomponents for entry to the bufferarea

– Anterooms must maintain ISOClass 8 air if they serve only abuffer area in which nonhazardous compounding isperformed

– If the anteroom also serves an HDbuffer room, then the anteroom isrequired to maintain ISO Class 7 air


• The Ante-area (anteroom) is theroom directly outside the bufferarea– This room is to perform hand

hygiene, garbing and stagecomponents for entry to the bufferarea

– Anterooms must maintain ISOClass 8 air if they serve only abuffer area in which nonhazardous compounding isperformed

– If the anteroom also serves an HDbuffer room, then the anteroom isrequired to maintain ISO Class 7 air

Facility Design “Shalls”

• Line of demarcation in anteroom or SCA• Furniture, equipment and physical plant

surfaces nonporous, smooth and cleanable• Climate conducive to comfort (68°F)• Materials limited to what is essential for

compounding• Ceiling: hydrophobic panels caulked around

perimeter• Floors: cleanable with coved molding• Walls: solid or locking panels impervious,

cleanable and non-shedding• Sink: hands-free water and soap


• Line of demarcation in anteroom or SCA• Furniture, equipment and physical plant

surfaces nonporous, smooth and cleanable• Climate conducive to comfort (68°F)• Materials limited to what is essential for

compounding• Ceiling: hydrophobic panels caulked around

perimeter• Floors: cleanable with coved molding• Walls: solid or locking panels impervious,

cleanable and non-shedding• Sink: hands-free water and soap

Polling Question

If an anteroom serves both a non hazardous buffer area and ahazardous drug buffer area, it must be which ISO aircleanliness classification?

1. Class 72. Class 83. Class 54. No Class


1. Class 72. Class 83. Class 54. No Class

Kate

Highlight

Facility Design “Shalls”

• Temperature of incubators conform torequirements

• Controlled room, cold and frozenenvironments are monitored and conform toUSP requirements

• Evidence that temperatures in all controlledareas are monitored at least daily anddocumented

• Evidence of effective mechanisms to– report excursions

– repair defects

– protect CSPs

– document actions


• Temperature of incubators conform torequirements

• Controlled room, cold and frozenenvironments are monitored and conform toUSP requirements

• Evidence that temperatures in all controlledareas are monitored at least daily anddocumented

• Evidence of effective mechanisms to– report excursions

– repair defects

– protect CSPs

– document actions

Equipment Related “Shalls”

• ACDs used for TPN/dialysis tested weekly forvolumetric/gravimetric accuracy

• Written PnP details maintenance, calibration andcleaning of all equipment and documented

• Equipment used for compounding or monitorcontrolled environments (e.g., ACDs, temperatureand humidity monitors, isolators, volumetric airsamplers, freezers, refrigerators, etc.)

– Cleaned

– Maintained

– Calibrated

• Personnel who used equipment have receivedtraining and demonstrated ability touse/troubleshoot


• ACDs used for TPN/dialysis tested weekly forvolumetric/gravimetric accuracy

• Written PnP details maintenance, calibration andcleaning of all equipment and documented

• Equipment used for compounding or monitorcontrolled environments (e.g., ACDs, temperatureand humidity monitors, isolators, volumetric airsamplers, freezers, refrigerators, etc.)

– Cleaned

– Maintained

– Calibrated

• Personnel who used equipment have receivedtraining and demonstrated ability touse/troubleshoot

Primary/Secondary Engineering Control “Shalls”

• If differential pressure design, then pressure gaugesinstalled and monitored at least daily:– Buffer anteroom (0.02” w.c. positive or 0.01”

negative)– Anteroomnon-classed (0.02” w.c. positive)

• If open concept (air displacement design):– Velocity across entire opening maintains 40

feet/minute and verified by smoke– Not allowed if HD compounding

• Air Cleanliness– Buffer ISO Class 7– Anteroom ISO Class 7/8

• Air Exchanges– Buffer room: at least 30 ACPH with 15 of those from

HEPA filtered air supplied to room– Ante-area: no requirement but at least 20 ACPH

common


• If differential pressure design, then pressure gaugesinstalled and monitored at least daily:– Buffer anteroom (0.02” w.c. positive or 0.01”

negative)– Anteroomnon-classed (0.02” w.c. positive)

• If open concept (air displacement design):– Velocity across entire opening maintains 40

feet/minute and verified by smoke– Not allowed if HD compounding

• Air Cleanliness– Buffer ISO Class 7– Anteroom ISO Class 7/8

• Air Exchanges– Buffer room: at least 30 ACPH with 15 of those from

HEPA filtered air supplied to room– Ante-area: no requirement but at least 20 ACPH

common


• Once PECs are placed, smokestudies were conducted to verifyunidirectional airflow in DCA

• PECs certified according to CETAguidelines (CAG-003-2006) orsimilar– BSCs: NSF/ANSI 49

• If LAFWs or BSCs not placed inISO Class 7, then compounding islimited to low risk level CSPs with12 hour BUD (non hazardous)


• Once PECs are placed, smokestudies were conducted to verifyunidirectional airflow in DCA

• PECs certified according to CETAguidelines (CAG-003-2006) orsimilar– BSCs: NSF/ANSI 49

• If LAFWs or BSCs not placed inISO Class 7, then compounding islimited to low risk level CSPs with12 hour BUD (non hazardous)


• Isolators not placed in ISO Class 7 must meetall of the following:– Maintain ISO Class 5 conditions during

dynamic operating conditions including duringtransfer of components and compounding

– Particle counts remain ISO Class 5 duringcompounding

– Not > 3250 particles 0.5μm and larger per m3

are counting during material transfer (withcounter probe nearest possible to transferdoor)

• Recovery time to achieve ISO Class 5 andwritten compounding procedures ensureadequate recovery time after materialtransfer and compounding.


• Isolators not placed in ISO Class 7 must meetall of the following:– Maintain ISO Class 5 conditions during

dynamic operating conditions including duringtransfer of components and compounding

– Particle counts remain ISO Class 5 duringcompounding

– Not > 3250 particles 0.5μm and larger per m3

are counting during material transfer (withcounter probe nearest possible to transferdoor)

• Recovery time to achieve ISO Class 5 andwritten compounding procedures ensureadequate recovery time after materialtransfer and compounding.

Secondary Engineering ControlsTest Non Haz Buffer Anteroom HD Buffer

Airflow 30 ACPH (at least 15 ACPH fromoutside the room)

Not specified but 20 ACPH isdesirable 30 ACPH; 12 ACPH if CACI is used

RoomSegregation

Minimum differential pressure of0.02” w.c. + from cleanroom to

anteroom and all adjacent spaces

Minimum differential pressure of0.02” w.c. + from anteroom to all

adjacent spaces

Minimum differential pressure of0.01” w.c. - from the HD

cleanroom to the anteroom.

If displacement airflow, then velocity of 40 feet/minute fromcleanroom to the anteroom across the entire opening

Not allowed in HD compounding

HEPA FilterLeak 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.


HEPA FilterLeak Test


SmokePatternTesting

Buffer rooms must be segregated from the ante-area and all other adjacent spaces with the doors closeusing smoke to observe airflow under dynamic operating conditions (with pharmacy staff compounding).

Non-ViableParticleCounts

ISO Class 7 ISO Class 8 unless it serves HDbuffer then ISO Class 7 ISO Class 7

Airborne particle counter used to samples particle levels in all locationsunder dynamic operating conditions.

Temperature No specific requirement other than comfortable typically a temperature of 68°F

Humidity Not a mandatory test but Relative Humidity between 35% and 60% is recommended

Adapted from CETA Certification Matrix for Sterile Compounding Facilities CAG-008-2010.

Traditional Primary Engineering Controls

TEST LAFW BSC(NSF International Criteria)

Placement of PrimaryEngineering Control

Placed in ISO Class 7 cleanroom; 0.2”w.c. or SCA

Placed in ISO Class 7 Cleanroom, 0.1”negative w.c. to anteroom

Airflow Velocity Velocity 80 to 100 feet/minute 6-12”from the filter

Downflow Velocity Profile and FaceVelocity Tests

HEPA Filter Leak TestHEPA filters must be certified to be

free from leaks > 0.01% of upstreamaerosol concentration

HEPA filters must be certified to be freefrom leaks > 0.01% of upstream aerosol

concentration or aerosol penetration not> 0.005% of upstream concentration

Verifies LAFW is free from unsealedconstruction joints & particles notbeing introduced into critical work

area

In BSCs, this test is called the PressureDecay/Soap Bubble Test and verifies thatthe cabinet is not leaking to the exterior


Backstreaming TestVerifies LAFW is free from unsealedconstruction joints & particles notbeing introduced into critical work

area

In BSCs, this test is called the PressureDecay/Soap Bubble Test and verifies thatthe cabinet is not leaking to the exterior

Airflow patterns smoke testAn observation using smoke to visualize airflow under dynamic operating

conditions (with pharmacy staff compounding) to confirm laminarity of the air isundisturbed

Site Installation AssessmentTests

Verifies that the BSC is properlyintegrated into the facility testing airflowand sash alarms; interlocks and exhaustsystem performance

Non-Viable Particle Counts Particles counters capable of detecting particles 0.5 μm are used to verify ISOClass 5 air conditions

Adapted from CETA Certification Guide for Sterile Compounding Facilities. CAG-003-2006-11 and NSF/ANSI 49-2012.

Unidirectional IsolatorsTest CAI CACI

Placement of PEC Preferably room/area devotedto compounding

Room certified to have at least 12 ACPH and be 0.1” w.c.negative to adjacent room

Airflow Velocity Measurement of actual airflow to manufacturer’s design intent. The main chamber is expressed asa range of feet/min with a designated % uniformity.

Chamber Pressure Test Determines that pass-through and main chamber pressures adequate to provide isolator separationbetween main chamber and ambient spaces. Pressure range determined by manufacturer.

Site Installation AssessmentTests

Tests to verify proper alarm function; pass-through door interlock function; and proper canopy orexhaust connection performance.

HEPA Filter IntegrityLeak Test


Particle Containment andEnclosure Leak Test

Test determines particle integrity of the cabinet at points ofpotential leakage; leaks detected do not exceed ISO Class 5 air

cleanliness.


Particle Containment andEnclosure Leak Test N/A

Test determines particle integrity of the cabinet at points ofpotential leakage; leaks detected do not exceed ISO Class 5 air

cleanliness.

Volatile HD ContainmentTest N/A Verifies that CACI is properly connected to exhaust and provides

personnel protection from volatilized HDs

Hazardous ParticleContainment Test N/A Verifies that CACI provides worker protection from the escape of

HD particles during compounding.

Airflow Smoke PatternTest

An observation using smoke to visualize airflow under dynamic operating conditions (withpharmacy staff compounding) to confirm laminarity of the air is undisturbed

Preparation Ingress andEgress Test

Determine if the pass-through system is capable of supporting material transfer while maintainingthe designated cleanliness classification during the transfer.

Non-Viable Particle Counts Particles counters capable of detecting particles 0.5 μm are used to verify ISO Class 5 air conditionsboth at rest and during dynamic operating conditions.

Adapted from CETA Compounding Isolator Testing Guide. CAG-002-2006.

General Environmental Sampling “Shalls”

• Detailed written PnP on all aspects ofenvironmental sampling

• Sampling occurs in all ISO areas from cleanest todirtiest ISO 5 ISO 7 ISO 8

• CFU Action Levels established

• Evidence of logical plan of action in the eventsampling exceeds Action Levels


• Detailed written PnP on all aspects ofenvironmental sampling

• Sampling occurs in all ISO areas from cleanest todirtiest ISO 5 ISO 7 ISO 8

• CFU Action Levels established

• Evidence of logical plan of action in the eventsampling exceeds Action Levels

CFU/m3 air/plate(1000 liters) If < 1000 liters air sampled, convert to equivalent AL (e.g., 400 liter sample in ISO Class 7 then AL = >4 CFU/plate)

ClassificationVolumetricAir SampleRequired*

ISO Class 5 > 1ISO Class 7 > 10ISO Class 8 > 100

Table 2 in Chapter <797>

Viable Air Sampling “Shalls”

• Viable air sampling performed:– at time of initial certification of PECs/SEC– every 6 months in association with physical

plant recertification– after major service or device relocation

• Air sampling performed with volumetricsampler (not settling plates or paddles)

• Air sampling volume at each location is 400 to1000 liters

• General growth medium and fungal specificmedium

• Evidence that if Action Level is exceeded, areais cleaned and resampled


• Viable air sampling performed:– at time of initial certification of PECs/SEC– every 6 months in association with physical

plant recertification– after major service or device relocation

• Air sampling performed with volumetricsampler (not settling plates or paddles)

• Air sampling volume at each location is 400 to1000 liters

• General growth medium and fungal specificmedium

• Evidence that if Action Level is exceeded, areais cleaned and resampled

Environmental Sampling “Shalls”


Growth Media

• Soybean Casein Digest Media(Trypticase Soy Broth/Agar) to supportthe growth of bacteria

• Malt Extract Agar or other media thatsupports the growth of fungi

• Must use plates with lecithin andpolysorbate 80 which are chemicalsthat neutralize cleaning agents whenperforming:– Surface sampling

– Personnel glove sampling associatedwith MFUs


• Soybean Casein Digest Media(Trypticase Soy Broth/Agar) to supportthe growth of bacteria

• Malt Extract Agar or other media thatsupports the growth of fungi

• Must use plates with lecithin andpolysorbate 80 which are chemicalsthat neutralize cleaning agents whenperforming:– Surface sampling

– Personnel glove sampling associatedwith MFUs

Sampling for Air Viable Organisms

• Volumetric air sampling isrequired– Predefined amounts of air

• Settling Plates cannot be theonly method of evaluating airviable organisms– Not qualitative– Settling of particles influenced

by size of particle and airmovement


• Settling Plates cannot be theonly method of evaluating airviable organisms– Not qualitative– Settling of particles influenced

by size of particle and airmovement

Courtesy of MSI, Inc. Houston, TX(www.microbiologyspecialists.com)

Actions to Take When Action Levels Exceeded

• An investigation into the sourceof the contamination must beconducted.

• Sources:– HVAC systems: changes externally

– Damaged HEPA filters

– Changes in personnel garbinghabits

– Changes in work practices

– Failure to follow PnP

– New employees


• An investigation into the sourceof the contamination must beconducted.

• Sources:– HVAC systems: changes externally

– Damaged HEPA filters

– Changes in personnel garbinghabits

– Changes in work practices

– Failure to follow PnP

– New employees

CFU Identification and Sources

Microorganisms IndicationStaphylococcus/ Micrococcus • Personnel habits or gowning problems

Gram negative rods • Water condensation, leaking, aerosols

Bacillus species • Dust, dirt, floor traffic, possible air handling

Molds • Influx of unfiltered air, mold from streetclothing or mold-contaminated cardboard,water reservoir, i.e. incubator humidificationsystem


• Influx of unfiltered air, mold from streetclothing or mold-contaminated cardboard,water reservoir, i.e. incubator humidificationsystem

Yeast • Possible outdoor air influx; clothing-borne,especially in late summer/ fall; possiblehuman contaminant

Diptheroids/ coryneforms • Poor air conditioning (leading to sweating andpersonnel discharge from gowns)

Source: Azzur Labs (www.azzurlabs.com)

Facility Inspector Evaluation Metrics

EnvironmentalSampling

Required Frequency in USPChapter <797>

Suggested Best PracticeFrequency

Gloved FingertipSampling(personnel metric)

• Initially during garbing x 3• During MFT every 6 months for

high risk• During MFT annually for

low/medium risk

• Initially during garbing x 3• During MFT weekly for high risk• During MFTs monthly for

low/medium risk

Surface Sampling(personnel metric)

• “Periodic”• SOPs define when, where and

how SS is performed

• Weekly for high risk• Monthly for low/medium risk


Surface Sampling(personnel metric)

• “Periodic”• SOPs define when, where and

how SS is performed

• Weekly for high risk• Monthly for low/medium risk

Non ViableParticle Counts(facility metric)

• Initial facility commissioning• Every 6 months during recert of

facility and engineering controlsin compounding areas

• As required

Viable VolumetricAir Sampling(facility metric)

• Every 6 months • Weekly for high risk• Monthly for low/medium

Facility Inspector Evaluation Metrics

• Facility Maintenance PnP

• Certification Documents

• Environmental Sampling Plan

• Documentation– Temperature– Pressure/Velocity– Daily ACD Calibration– Annual testing other equipment such as freezers, incubators,

refrigerators, etc according to NIST standards


• Facility Maintenance PnP

• Certification Documents

• Environmental Sampling Plan

• Documentation– Temperature– Pressure/Velocity– Daily ACD Calibration– Annual testing other equipment such as freezers, incubators,

refrigerators, etc according to NIST standards

Facility Inspector Certification Report Metrics

• Does report reference CETA guidelines?

• Were particle counts performed under dynamic operating conditions?

• Was smoke testing ever performed and if so, was it performed underdynamic operating conditions?

• Was viable air sampling performed in all ISO classed areas?

• Was viable air sampling performed under dynamic operating conditions?

• Was viable air sampling performed based on the pharmacy’sEnvironmental Sampling Plan?

• If viable air sampling was performed, was any growth speciated to thegenus level?

• Is there any evidence that the pharmacy reviewed the VAS results andspeciation and took appropriate actions, if any?


• Does report reference CETA guidelines?

• Were particle counts performed under dynamic operating conditions?

• Was smoke testing ever performed and if so, was it performed underdynamic operating conditions?

• Was viable air sampling performed in all ISO classed areas?

• Was viable air sampling performed under dynamic operating conditions?

• Was viable air sampling performed based on the pharmacy’sEnvironmental Sampling Plan?

• If viable air sampling was performed, was any growth speciated to thegenus level?

• Is there any evidence that the pharmacy reviewed the VAS results andspeciation and took appropriate actions, if any?

Polling Question

Daily cleaning of a non hazardous primary engineering control(LAFW or CAI) begins with which of these?

1. Sterile 70% IPA2. Germicidal detergent diluted

with tap water3. Germicidal detergent diluted

with SWFIrrig4. Any of these


1. Sterile 70% IPA2. Germicidal detergent diluted

with tap water3. Germicidal detergent diluted

with SWFIrrig4. Any of these

Kate

Highlight

Polling Question

Daily decontamination and cleaning of a primary engineeringcontrol used for HD compounding (BSC or CACI) begins withwhich of these?

1. Germicidal detergent dilutedwith SWFIrrig

2. Germicidal detergent dilutedwith tap water

3. Dilute bleach or sodiumthiosulfate

4. Sterile 70% IPA


1. Germicidal detergent dilutedwith SWFIrrig

2. Germicidal detergent dilutedwith tap water

3. Dilute bleach or sodiumthiosulfate

4. Sterile 70% IPA

Kate

Highlight

Cleaning and Disinfection "Shalls”

• Written PnP detailing cleaning agents, non-shedding wipes, mop materials, procedure,frequency and documentation.

• Personnel who perform cleaningsuccessfully complete– Hand hygiene and garbing competency

– Cleaning and Disinfection competency

• Floors and easily cleanable horizontalsurfaces in the buffer area, anteroom andSCA are cleaned daily with designatedcleaning agent

• Walls, ceilings, empty shelving, supply binsare cleanedmonthly with designatedcleaning agent


• Written PnP detailing cleaning agents, non-shedding wipes, mop materials, procedure,frequency and documentation.

• Personnel who perform cleaningsuccessfully complete– Hand hygiene and garbing competency

– Cleaning and Disinfection competency

• Floors and easily cleanable horizontalsurfaces in the buffer area, anteroom andSCA are cleaned daily with designatedcleaning agent

• Walls, ceilings, empty shelving, supply binsare cleanedmonthly with designatedcleaning agent


• Only trained compounding personnel cleaninside of the ISO Class 5 areas

• ISO Class 5 critical work area disinfected:– Beginning of each work shift

– Between batches

– Every 30 minutes continuous compounding

– After spills

– Anytime contamination is suspected

• Sterile 70% IPA (sIPA) remains in contactwith the surface being disinfected for 10-30seconds and allowed to dry beforecompounding is started


• Only trained compounding personnel cleaninside of the ISO Class 5 areas

• ISO Class 5 critical work area disinfected:– Beginning of each work shift

– Between batches

– Every 30 minutes continuous compounding

– After spills

– Anytime contamination is suspected

• Sterile 70% IPA (sIPA) remains in contactwith the surface being disinfected for 10-30seconds and allowed to dry beforecompounding is started


• Equipment that is reused is labeled anddedicated according to area of use

• Mops, wipes, etc. are non-shedding


Polling Question

Where is a germicidal detergent used in daily cleaning?

1. Floors and easilycleanable horizontalsurfaces in buffer area,anterooms and SCAs

2. Floors only in buffer area,anteroom and SCAs

3. All floors, easily cleanablehorizontal surfaces andinside ISO Class 5 spaces


1. Floors and easilycleanable horizontalsurfaces in buffer area,anterooms and SCAs

2. Floors only in buffer area,anteroom and SCAs

3. All floors, easily cleanablehorizontal surfaces andinside ISO Class 5 spaces

Kate

Highlight

Use of Disinfectants

• Must be germicidal detergent• Dilution of agent is critical to its efficacy• Contact time• Storage conditions: light or temperature sensitive• Follow manufacturer instructions


Resistance and Rotation of Cleaning Agents

“The development of microbial resistanceto disinfectants is less likely, asdisinfectants are more powerful biocidalagents than antibiotics and are applied inhigh concentrations against lowpopulations of microorganisms usually notgrowing actively, so the selective pressurefor the development of resistance is lessprofound.”“It is prudent to augment the daily use of abactericidal disinfectant with weekly (ormonthly) use of a sporicidal agent.”


“The development of microbial resistanceto disinfectants is less likely, asdisinfectants are more powerful biocidalagents than antibiotics and are applied inhigh concentrations against lowpopulations of microorganisms usually notgrowing actively, so the selective pressurefor the development of resistance is lessprofound.”“It is prudent to augment the daily use of abactericidal disinfectant with weekly (ormonthly) use of a sporicidal agent.”

Excerpted from USP Chapter <1072> Disinfectants and Antiseptics

Polling Question

USP <797> requires use of sterile water to dilute cleaningagents inside of primary engineering controls?

1. True2. False


Kate

Highlight

When to use Sterile Water?

• Sterile water (SWInj or SWIrrig) should be usedto dilute disinfectant solutions used inside ofthe ISO Class 5 areas

• Though these areas and cleaning supplies arenot sterile, use of sterile water reducespyrogens and potential bioburden


• Sterile water (SWInj or SWIrrig) should be usedto dilute disinfectant solutions used inside ofthe ISO Class 5 areas

• Though these areas and cleaning supplies arenot sterile, use of sterile water reducespyrogens and potential bioburden

Type Water CFU/mL* Pyrogens*

Tap Water 500 100 EU/mL

Purified Water 100 0.25 EU/mL

Water for Injection < 10 < 0.25 EU/mL*Sources: USP NF defines standards for Purified water and Water for Injection; US EPA definesdrinking water standards

Establishing a Program

• Work with Infection Controldepartment

• If building new facility, design forcleaning

• Important to understand designand materials of construction– Determine required

materials/equipment– Assess compatibility of agents

• Develop procedure– What, when, where and how– Agent rotation– Consider existing organizational

policies or procedures

• Train personnel to procedure• Document cleaning activities

performed• Monitor adequacy of program

– Environmental sampling– Observation


• Work with Infection Controldepartment

• If building new facility, design forcleaning

• Important to understand designand materials of construction– Determine required

materials/equipment– Assess compatibility of agents

• Develop procedure– What, when, where and how– Agent rotation– Consider existing organizational

policies or procedures

• Train personnel to procedure• Document cleaning activities

performed• Monitor adequacy of program

– Environmental sampling– Observation

More than Daily* Daily MonthlyISO Class 5 PEC & worksurfaces• Beginning of day/shift• Prior to each batch• Every 30 min• When visibly soiled• As spills occur• Suspect contaminationEmpty trash as needed

Empty trashISO Class 5 PEC**Easily cleanable horizontalsurfaces in ante andcleanrooms (including pass-through counter)Restock daily supply cartFloors from furthestlocation in cleanroom outthru anteroom (includingpass-through floor)

Empty trashCeilingWalls, Pass-throughsEvery surface• Outside of PECs• All carts (top, bottom,

wheels, etc.)• Supply bins• Doors, handles, ventsISO Class 5 PEC**Restock supply cartFloors (same as daily)Clean refrigerators, freezers,incubators, etc.


ISO Class 5 PEC & worksurfaces• Beginning of day/shift• Prior to each batch• Every 30 min• When visibly soiled• As spills occur• Suspect contaminationEmpty trash as needed

Empty trashISO Class 5 PEC**Easily cleanable horizontalsurfaces in ante andcleanrooms (including pass-through counter)Restock daily supply cartFloors from furthestlocation in cleanroom outthru anteroom (includingpass-through floor)

Empty trashCeilingWalls, Pass-throughsEvery surface• Outside of PECs• All carts (top, bottom,

wheels, etc.)• Supply bins• Doors, handles, ventsISO Class 5 PEC**Restock supply cartFloors (same as daily)Clean refrigerators, freezers,incubators, etc.

* Clean PEC with sterile 70% IPA** Clean with germicidal detergent diluted with SWf Irrigation followed by sterile 70% IPA; use decontamination first agent if HD PECRed represents best practice recommendation; Black indicates 797 required

What’s the same? What’s different?1. Complete hand hygiene & garbing

appropriate to compounding area

2. Cleaning solution is germicidal detergent;sporicidal may be rotated in weekly/monthly

3. Cleaning solution prepared in containerdedicated for use in ISO Class 5 areas &documented

4. All surfaces cleaned with cleaning agentdiluted with sterile water

5. Use low-linting wipes and/or tools dedicatedto ISO Class 5 areas

6. Disinfect all surfaces with sIPA after cleaning

7. Order of cleaning with cleaning agent andIPA:

Ceiling

Back

Sides, IV bar and hooks

Anything in PEC

Deck

LAFW: SameIntegrated VLF: Same except

Surfaces need to be reached with mop Clean/disinfect inside surface of Lexan®

CAI: Same except Surfaces may need to be reached with isolator tool (preferable to

open CAI if in controlled space) Surfaces of ante-chamber are decontaminated and cleaned before

the main chamber and in same order

BSC: If used for HD, same except Add 1st step: deactivate HD residue on all surfaces with appropriate

agent followed by cleaning agent and sIPA Additional surface to decontaminate/clean (inside of the sash view

screen) PPE/trash from decontamination discarded in black RCRA bag; rest

discarded in yellow HD trace trash.


1. Complete hand hygiene & garbingappropriate to compounding area

2. Cleaning solution is germicidal detergent;sporicidal may be rotated in weekly/monthly

3. Cleaning solution prepared in containerdedicated for use in ISO Class 5 areas &documented

4. All surfaces cleaned with cleaning agentdiluted with sterile water

5. Use low-linting wipes and/or tools dedicatedto ISO Class 5 areas

6. Disinfect all surfaces with sIPA after cleaning

7. Order of cleaning with cleaning agent andIPA:

Ceiling

Back

Sides, IV bar and hooks

Anything in PEC

Deck

BSC: If used for HD, same except Add 1st step: deactivate HD residue on all surfaces with appropriate

agent followed by cleaning agent and sIPA Additional surface to decontaminate/clean (inside of the sash view



CACI: If used for HD same except Add 1st step: deactivate HD residue on all surfaces with appropriate

agent followed by cleaning agent and sIPA Surfaces may need to be reached with isolator tool (preferable to

open CACI if in controlled space) Surfaces of ante-chamber are decontaminated and cleaned before

the main chamber and in same order Additional surface to decontaminate/clean (inside of the sash view



Inspector Evaluation Metrics: Competency


Inspector Evaluation Metrics: Cleaning

• Observe staff performing daily clean (if possible)• When you are in the controlled environments check the following:

– Returns– Storage of cleaning agents, supplies and equipment– Inside supply bins– Behind and on sides of hoods


No roomto clean

Cleaning Logs

• Do forms reflect written policy andprocedure?

• Are written SOPs and forms sufficientlydetailed?

• Are staff trained on PnP?• Are forms complete?• Is monthly cleaning performed at

approximately the same time of month?














Summary

• Building a compliant facility isn’t enough!• Maintaining the facility and regularly measuring and

adjusting its performance during regular service fromCertification professionals is necessary.

• Vigilance and adherence to proper cleaning and otherwork practices are required to maintain a state ofcontrol.

• Environmental Sampling provides the ongoing evidenceof the effectiveness of the facility, cleaning and workpractices in achieving an environment that is suitablefor compounding sterile preparations.


• Building a compliant facility isn’t enough!• Maintaining the facility and regularly measuring and

adjusting its performance during regular service fromCertification professionals is necessary.

• Vigilance and adherence to proper cleaning and otherwork practices are required to maintain a state ofcontrol.

• Environmental Sampling provides the ongoing evidenceof the effectiveness of the facility, cleaning and workpractices in achieving an environment that is suitablefor compounding sterile preparations.