What are the PEC and C-PEC? What are NAPRA requirements in regards to PEC and C-PEC?

PEC, standing for Primary Engineering Control, is an umbrella term for devices that provide ISO Class 5 environment during sterile non-hazardous compounding. The primary goal of a PEC is to protect the compound/product during the compounding process. This is achieved through passing unidirectional and ‘filtered to ISO 5’ air over the compounding process. PEC is not suitable for sterile hazardous compounding.

C-PEC, Containment Primary Engineering Control, refers to a PEC that protects the personnel and environment as well as the compound, hence the notion of containment. The triple protection is required during sterile hazardous compounding.

The term C-PEC may also loosely refer to other containment devices that protect only personnel and environment. For example, non-sterile compounding (level A, B, and C), in which sterility is not required but protection of personnel and environment is still needed. A common case for this is powder containment hoods.

Below is a brief description of some the most common PEC/C-PEC devices along with required test and certification according to NAPRA.

PEC / Sterile Non-Hazardous Compounding

ü LAFW (Laminar Airflow Workbench/Workstation), also known as LAFS (Laminar Airflow System), clean bench, or laminar flow hood, is a PEC and therefore it is utilized in sterile non-hazardous compounding. It is available in two types: Vertical flow and Horizontal flow. The only difference is whether the filtered air is directed from top to bottom or from the back/baffle/diffuser coming toward the technician/pharmacist. While the functionality is similar, some may prefer one over another due to their hand position and technics during aseptic processes.

Important Note: A PEC must operate continuously during every sterile compounding activity

Important Note: LAFW must be positioned in an ISO class 7 cleanroom that is adjacent to an ISO class 8 anteroom

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EducationalNewsletter OCTOBER2018Issue:PEC,C-PEC,andNAPRArequirements

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Figure1:ConceptualdrawingsofhorizontalandverticalLAFWs(sideviews)

ü CAI (Compounding Aseptic Isolator), also known as RABS (Restricted Access Barrier System), positive pressure isolator, or positive pressure glove box is a PEC.

Figure2:ConceptualdrawingofaCAI(frontview)

Test and Certification of LAFW: NAPRA has adopted CETA Application Guide, CAG-003, for test and certification of LAFW.

Required tests: airflow velocity testing, HEPA filter leak test, Induction leak test, airflow smoke pattern test (shall be performed under “dynamic conditions”), and non-viable particle counting (verification of ISO 5 environment). Required frequency: every 6 months, when relocated or repaired, when viable air sampling results do not comply with specification.

RoomAir

MainChamber(++pressure)

Pass-throughChamber(+pressure) ISO5Air

HEPAFilter

Blower

Usedairrecirculatedbackintotheroom

ISO5Air

HEPAfilter

Airintake

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CAI is utilized in sterile non-hazardous compounding. It usually has two chambers, “transfer, pass-through, or antechamber” and “main”. Both chambers are positively pressured, with main one having the higher relative pressure.

C-PEC / Sterile Hazardous Compounding

ü CACI (Compounding Aseptic Containment

Isolator), also known as RABS (Restricted Access Barrier System), negative pressure isolator, or negative pressure glove box is a C-PEC. Hence it is used in sterile hazardous compounding. The main chamber is negatively pressured for containment purposes and protection of personnel and surrounding area/environment. The pressure of pass-through chamber is positive relative to the main chamber but negative relative to the cleanroom or segregated area. The pressure settings of the two chambers may vary according to manufacturer’s design.

Test and certification of CAI: NAPRA requires test and certification of CAI in accordance with CAG-002.

Required tests: airflow test, chamber pressure test, installation assessment test, HEPA filter leak test, recovery time test, smoke pattern test, ingress and egress test, and non-viable particle counting (verification of ISO 5 environment).

Required frequency: every 6 months, when relocated or repaired, when viable air sampling results do not comply with specification. Required frequency: minimum every 6 months.

Important Note: A C-PEC for sterile hazardous compounding

- Must be externally ventilated - Must operate continuously, 24 hours a day - Must be connected to a notification system

Important Note: CAI must be positioned in an ISO class 7 cleanroom that is adjacent to an ISO class 8 anteroom. However, a CAI may be positioned in a room where particle count exceeds ISO class 7. In this case limitation to the compounding activities are applied:

- Only BUD of 12 hours or less - Only low risk preparation - One preparation at a time - Preparation are compounded in reserved area for sterile compounding and fulfilling a few logistic

and facility requirements - Compliant personnel and required SOPs

Important Note: CACI must be positioned in an ISO class 7 cleanroom or better, under negative pressure that is adjacent to an ISO class 7 anteroom. However, a CACI may be positioned in a room where air particles exceed ISO class 7. In this case limitation to the compounding activities are applied:

- CACI must be in a segregated area with -2.5Pa relative pressure and minimum 12 ACPH - Only BUD of 12 hours or less - Only low or medium risk preparation - One preparation at a time - Preparation are compounded in reserved area for sterile compounding and fulfilling a few logistic

and facility requirements - Compliant personnel and required SOPs

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Figure3:ConceptualdrawingofaCACI(sideview)

ü BSC (Biological Safety Cabinet or Bio-Safety Cabinet) Class II is designed to provide protection of

compound, personnel, and environment. Hence as a C-PEC, Class II is used in sterile hazardous compounding and may be an alternative solution to CACI. BSC II pushes a curtain of ISO 5 air over the DCA (direct compounding area) to provide sterility while at the same time acting as a containment ventilated enclosure. BSC II itself has 4 types of A1, A2, B1, and B2. Types A1 and A2 exhaust about 30% of the intake air and recirculate about 70% back into the BSC for reuse (passes through HEPA again for ISO 5 compliance). Intake airflow velocity is 75 ft/min for A1 and 100 ft/min for A2. The other difference is that in case of A2, all the plenums must be under negative pressure. USP 800 does not allow type A1 for sterile hazardous compounding. While NAPRA does not differentiate between the Class II types, it requires the BSC II to be placed inside “ISO class 7 cleanroom under negative pressure and adjoined by ISO class 7 anteroom”.

Figure4:ConceptualdrawingoftypesA1andA2

Test and certification of CACI: NAPRA requires test and certification of CACI in accordance with CAG-002.

Required tests: airflow test, chamber pressure test, installation assessment test, HEPA filter leak test, containment integrity and enclosure leak test, recovery time test, smoke pattern test, ingress and egress test, and non-viable particle counting. There is also one other particular test that must be done on CACI according to CAG-002, though NAPRA has not mentioned it. That is gauntlet breach air velocity test.).

Required frequency: every 6 months, when relocated or repaired, when viable air sampling results do not comply with specification.

AirintakeA1:75ft/minA2:100ft/min

DuctedthroughCanopyAndconnectedtotheexhaustsystem

Airintake

Contaminatedair

30%exhausted.70%re-filteredandrecirculatedforreuse

Mixedairexhausted

IncaseofA2,allplenumsareunderorsurroundedbynegativepressure

ISO5Air

RoomAir

ISO5Air

ContaminatedAirAir

MainChamber(--pressure)

Filteredairductedtotheexteriorofthebuilding

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NAPRA requires the BSC Class II to be ducted out to the exterior of the building. In order to exhaust the Class II type A1 or A2 a canopy connection is mandatory. Straight (hard) ducting is not permitted for the A1 and A2. BSC Class II type B1 exhaust about 70% of intake air and recirculates/reuses about 30% of it. Canopy connection is not permitted, and the BSC must be hard ducted to the exhaust system.

Figure5:ConceptualdrawingoftypeB1

BSC Class II type B2 exhausts 100% of the intake air. It is sometimes referred to as the “total exhaust” version.

All four types, HEPA filter both recirculated and exhausted air. B2 provides higher level of protection in comparison to B1, B1 higher than A2, and A2 higher level of protection than A1. Selection of the right type requires a risk assessment of the compounding activities. The installation as well requires careful planning and connection to the exhaust system through canopy or direct duct.

Figure6:ConceptualdrawingoftypeB2

ISO5Air

70%exhausted30%recirculatedforreuse

Airintake

Contaminatedair

Contaminatedair

AirintakeHarddustedtotheexhaustsystem,100%exhausted

Airintake

ISO5Air

Important Note: BSC Class II must be positioned in an ISO class 7 cleanroom or better, under negative pressure, that is adjacent to an ISO class 7 anteroom.

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ü BSC Class III provides the highest level of protection for the personnel and environment. It is a gas-tight enclosure designed for highly infectious and hazardous processes. While 100% of the air intake is exhausted to the exterior of the building, it must pass through two HEPA filters in series. Both NAPRA and USP 800 allow use of Class III for sterile hazardous compounding. However, it is recommended the compounding activity should justify the use of Class III as it could be an overkill and costly to purchase and operate one.

C-PEC / Non-Sterile Compounding

ü BSC (Biological Safety Cabinet or Bio-Safety Cabinet) Class I: Class I BSC may as well be loosely referred to as CVE (containment ventilated enclosure), powder containment hood, safety enclosure, balance enclosure, or safety hood. ‘BSC Class I’ does not provide ISO class 5 air. So it is suitable for non-sterile compounding only. ‘BSC I’ or its siblings named above, solely provide protection for personnel and environment. While these names may be used interchangeably, there are minor differences to note.

Figure7:ConceptualdrawingofaCVE

BSC or CVE in most cases is the proper device capable of handling level C compounding. It may be ducted to the outside, utilizing single layer of HEPA filter, or may utilize two filter in series (redundant filter), and recirculate air back into the compounding room or lab.

Test and certification of BSC Class II: While CETA application guides are adopted for test and certification of class II, CETA guide refers to ANSI/NSF 49 for the test and certification of Class II and merely adds a particle count to the procedure.

Required tests: measurement of air supply, air intake velocity, smoke pattern, HEPA leak test, interlock system test, device calibration, and particle count test.

Required frequency: every 6 months, when relocated or repaired, when viable air sampling results do not comply with specification.

Test and certification of BSC Class III: according to manufacturer’s recommendation.

Required frequency: every 6 months, when relocated or repaired, when viable air sampling results do not comply with specification.

The term C-PEC is mainly used for sterile hazardous compounding. However, the term has been lent to the non-sterile compounding as well. In such case, it’s important to note that C-PEC for non-sterile do not provide ISO Class 5 air. They only provide protection for the personnel and environment.

Airintake

HEPAfilter

Exhaustedair

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Powder Hood is most common type in pharmacy settings used in non-sterile compounding. Considering the recent NAPRA guide on non-sterile compounding, these hoods may be proper for level A and B compounding but majority lack the requirement of level C compounding (That is possibility of being ducted to the exterior of the building or having redundant filters each capable of being tested separately)

Balance Enclosure is designed to eliminate the vibration caused by the blower or motor. The vibration may cause inaccuracy or problem with calibration of the balance.

Figure8:Conceptualdrawingofacontainmentventilatedenclosurewithredundantfilters

Fume Hood is capable of handling highly volatile, hazardous, and at times large volume of chemicals. Majority of fume hoods are ducted to the exterior of the building through high performance exhaust systems and complying with local building codes. Recent developments resulted in variety of filters (carbon filters) capable of cleaning the air off various chemical and hazards and recirculating it back to the lab environment. Although fume hood is not same as BSC it maybe used in non-sterile compounding of all levels if the hood is setup properly.

HEPAfilter

HEPAfilter

Airintake

Doublefilteredairisrecirculatedbacktothesurroundingenvironment

Test and certification of BSC I / CVE / powder hood: NAPRA requires leak test for the HEPA filter, and manufacturer’s recommended test for the device itself. These tests are required at least every six months. While manufacturers, and test and certification companies unanimously follow IEST-RP-CC-034 for filter leak test, the performance of the BSC itself may be a subject of disagreement on which guide or standard to follow. ASHRA 110 has long been used for testing of fume hoods. A Canadian equivalent to ASHRA 110 is CSA Z316.5. The methodology in these standard has been developed with input from industry and manufacturers and can be used for similar devices in the family of ventilated enclosures. CETA may, in future, provide a guideline for testing of BSC I or CVE. Required frequency: every six months, and when relocated or repaired.

A C-PEC utilized for level C compounding is required to be preferably exhausted to the exterior of the building. However, if not exhausted, redundant HEPA filter is acceptable. If C-PEC is contributing to create the negative pressure for the C-SEC/compounding room/segregated area, it must be ON 24/7.

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NextIssue,November2018:C-SECrequirements,acomparisonbetweenUSP800andNAPRAmodelstandardfornon-sterilecompounding.IncludestipsforturningacurrentroomintoaNAPRAcompliantspace.