Hospital Pharmacy Isolator Solutions for USP

Hospital Pharmacy Isolator Solutions for USP <797> Compliance from Esco

Contents

1. Introduction2. Clean Air Devices and Isolators3. Cytotoxic Exposure4. Esco Pharmacy Isolator (Positive Pressure Model)

- Main Features- Isolator Airflow- Maximum Patient Protection and Sterility- Ergonomic Enhancements- Isolator Construction- Microprocessor Control- Factory Testing and Validation

5. Isolator Operating Protocol

Introduction

Pharmacy is the health profession that links health science with chemical science, and it is charged with ensuring the safe use of medication.

Pharmacies:Compound and dispense medication in accordance with physician’s instructions.Provide patient care services including reviewing medications and providing drug use information.

Introduction

Prescription

Order to Pharmacy

Order to Nurses

Preparation of Worksheets/labels

Preparation of drugs

Administration

Introduction

Pharmacy compounding is the practice of preparing drugs in new forms and is one of the pillars of new drug development.

Physicians often prescribe compounded medicines for patients with unique health needs, because they are able to tailor a prescription to each individual patient and best meet their needs.

Introduction

Compounding is indispensable in the following situations:Patients requiring limited dosage strengths and dosage forms(e.g., infants) Patients with drugs allergies to certain ingredientsVeterinary medicine Pediatrics (e.g., making a medicine more palatable to children with flavor additives)Home health care

Introduction

Brutal incidents involving pharmacy compounding:Georgia, USA, March 2001

– 4 patients hospitalized-severe adverse reactions – Ingested a compounded thyroid medication– 1,000 times ordered dose

Florida, USA, July 2001– Aerosol medications contaminated and have little or no active ingredient, 3

patients died– Pharmacists and others convicted of defrauding Medicare

North & South Carolina, USA, September 2002– 1 patient died & 3 suffer adverse event of fungal meningitis– Source contaminated Methylprednisolone

These incidents were an alarm for pharmacies to re-evaluate present practices and controls.

Introduction

A compounded sterile preparation (CSP) is a dosage unit with any of the following characteristics:

Preparations prepared according to the manufacturer's labeled instructions.Preparations containing non-sterile ingredients/ components/ devices that need to be sterilized before use.

U.S Pharmacopoeia (USP) is a private organization formed in 1820. Current members include:

Accredited schools of medicine and pharmacyState medical and pharmacy associationsGovernment agencies, consumer organizations and others

Introduction

USP <797>, enacted Jan 1, 2004 was written to improve the compounding of sterile products.

It is the first official and enforceable requirement for CSPsThe Chapter’s requirements are applicable in all practice settings where sterile preparations are compounded

By setting standards, requirements, and procedures for CSPs, USP <797> reduces the potential for contamination caused by environmental contamination, pharmacist error, lack of quality assurance, incorrect beyond-use dating, and other factors.

Introduction

Specific issues USP <797> addresses: The responsibility of compounding personnel to ensure that CSPs are prepared, stored, dispensed, and distributed safelyContamination risk levelsProcedures to verify the accuracy and sterility of CSPsPersonnel training and evaluationVerification of Automated Compounding Devices (ACDs)Environmental quality and control

Clean Air Devices and Isolators

USP <797> engineeringcontrol requirements:

Laminar flow or biological safetycabinet in an ISO Class 7 cleanroom

An isolator with work zonecleanliness of ISO Class 5(cleanroom not required)


Factors Which Influence Sterility of the Work Zone

“Open Front” Laminar Flow and Biological

Safety Cabinets

Air-Tight Isolator

Cabinet placement, i.e.-Away from doors-Away from pedestrian traffic

Heavily Dependent Independent

Operator technique: i.e.-Gloves over cuffs-Aseptic technique

Heavily Dependent Less Dependent

Environmental factors i.e. room air cleanliness

Heavily Dependent Less Dependent


Pressure Regime Positive Negative(Re-Circulating)

Negative(Total Exhaust)

Non Hazardous Compounding

Yes Yes Yes

Hazardous Compounding(e.g. Chemotherapy)

No Yes Yes

Hazardous Drugs which May Volatilize

No No Yes

Isolator Types and ClassificationEsco offers 3 types of isolators for varying applications

4’ / 1.2m positive pressure model may be ordered in Oct 2007 with deliveries commencing in Nov / Dec 2007


Positive pressure inside work zone maintains sterility even in case of a breach in the barrier.

Suitable for non-hazardous compounding applications :TPN (Total Parental Nutrition); eye-drops; infusion; syringes, etc.

Positive Pressure Model

5-10% (exhaust back to the room)

80-90%Re-circulating Air


Negative pressure inside work zone maintains operator protection even in case of a breach in the barrier:

Suitable for compounding of hazardous drugs which will not volatilize i.e. Chemotherapy

Negative Pressure Model(Recirculating)

10-20% (exhaust back to the room)

80-90%Re-circulating Air


Negative pressure to ensure operator’s safety even in case of breach of barrier isolation system

Suitable for compounding of hazardous drugs which may volatilize i.e. Chemotherapy

Negative Pressure ModelTotal Exhaust

Connected to Exhaust

100% exhaust

Cytotoxic Exposure

Four routes of Cytotoxic Exposure:InhalationDermal absorptionIngestion of contaminated foodstuffs or mouth contact with contaminated handsAccidental injection

Cytotoxic Exposure

Acute– Gastrointestinal i.e. Nausea– Irritation to eyes, mucous membranes– Respiratory – occupational asthma to mitoxantrone– Dermatological i.e. rashes, dryness, irritation, hair loss

Chronic– Mutagenecity– Developmental and reproductive effects i.e. increased fetal loss, low birth weight,

infertility– Cancer Risks

Negative pressure isolators eliminate most of the four routes of cytotoxic exposure; hence, reduce the risk to personnel.

Esco Hospital Pharmacy Isolator

Positive Pressure Model

Features and BenefitsULPA filters with a typical efficiency of 99.999% at 0.1 to 0.3 microns provide superior ISO Class 3 air cleanliness, 100 times better than competing products.Work zone and pass-thru are under positive pressure relative to the external environment in order to maintain sterility in case of a breach in the barrier isolation system.Robust dual-wall construction. All positive pressure work zones are surrounded by negative pressure plenums at the sides and back for guaranteed safety.Sentinel Gold™ Microprocessor controller supervised all functions and monitors airflow and pressures in real-time.



Features and BenefitsAngled front and oval gloveports improve reach and comfort.Safe-change cuff rings permit glove changes with zero risk of contaminating the work zone.Easy-to-clean one piece work zone liner with no crevices.External surfaces are coated with Esco Isocide™ antimicrobial coating to protect against surface contamination and inhibit bacterial growth. Isocide™ eliminates 99.9% of surface bacteria within 24 hours of exposure.Optional sharps disposal system improves workflow.Optional hydraulic stand enables work height adjustment.


Positive Pressure Isolator Airflow ULPA-filtered laminar airflow in work zone and pass-thru ensures ISO Class 3 cleanliness.Air in work zone and pass-thru is pulled below the work surface and behind the work zone into the blower plenum.This combines with some ambient air entering through an inlet filter.90% of the total is re-circulated as laminar airflow in the work zone and pass-thru.10% of the total is exhausted through an ULPA filter to prevent heat build-up.


Isolator FiltrationAdvanced separatorless mini-pleated ULPA filters are tested to >99.999% efficiency for 0.1-0.3 micron particulates, significantly better than conventional HEPA filters.ISO Class 3 air cleanliness in work zone, 100 times better than competing products.

Clean Air Recovery Laminar airflow within work zone and pass-thru enables recovery of chamber atmosphere to ISO class 3 conditions within 3 minutes.Entire work zone air is changed 20-30 times per minute.


Pass Thru, Vertical Sliding Inner DoorMinimizes ingress of contamination into the work zone during transfer procedure compared with conventional swing door design.Maximizes the effective work area in the work zone.


Horizontal Sliding TrayEliminate having to reach into the pass-thruMinimizes operator fatigue during transfer procedures

Optional Sharps Disposal SystemEnables smoother work flow and minimizes cross contamination.Sharps may be disposed through the work surface into disposal bins while minimizing contamination of the work zone.


Optional Sharps Disposal System Interface between sharps disposal bin and isolator is aerosol tight to avoid ingress of contamination during the disposal operation.


Safe-Change Cuff RingsGlove changes with no risk of contaminating the work zone.

1 2

Push old glove into the sleeve Remove both O-rings


3 4

Move the bead of the old glove to the forward groove

New glove is stretched over the old glove, with its bead in the rear groove



5

With the new glove in place, the bead of the old glove is gradually eased out of its place and into the sleeve for removal. O-rings are secured.




Ergonomic EnhancementsErgonomically styled sloped front reduces glare and allows for easier reach into the work area.Oval shaped gloveports improve reach into the work zone compared with conventional circular ports.


Ergonomics Enhancements Optional hydraulic stand enables the work surface height to be adjusted to fit the operator, for both sitting and standing operation.Common surgical gloves attach to the cuff ring and may also be used, depending on operator preference.Push-bar handle enhances mobility.

Isolator ConstructionCabinet interior is constructed of durable and pharmaceutical-grade 304 stainless steelSingle piece stainless steel work surface is easy to clean.


Isolator ConstructionRaised edges on all sides with large radius corners to contain spillage and simplify cleaningWork zone has no welded joints to collect contaminants or rust


Isolator ConstructionHinged access window can be opened fully for loading large equipment and for cleaning purpose


Isolator ConstructionCabinet exterior is constructed of industrial-grade electro-galvanized steelExternal surfaces are coated with Esco ISOCIDE™ antimicrobial coating to protect against surface contamination and inhibit bacterial growth


Microprocessor Control Sentinel™ Gold Controller with multi line LCD displayWork zone and pass-thru pressures and downflow velocity are monitored with alarms and displayed on the LCD screen.



Factory Testing and Validation

Filter Leak Tests verify the integrity of the ULPA filters as-installedDownflow Velocity Tests verify adequate laminar air flow velocitiesPressure Test measures work zone and pass-thru pressuresParticle Counts (Air Cleanliness Tests) verify air cleanliness in accordance with ISO 14644-1


Factory Testing and Validation

Product Ingress and Egress Tests determines if the isolator work zone can maintain ISO Class 3 during transfer proceduresRecovery Time Test determines the amount of time the main chamber takes to recover to ISO Class 4 in the event of a contamination eventBreach Test verifies product protection in case of a glove failure.Operator Comfort Tests include noise, light and vibration.

Isolator Operating Protocol

Basic Laboratory PracticeWear gloves: regular changing of gloves, double gloveWear gowns: vinyl coating, polyethylene coating recommendedWear masks: N-95 mask when compoundingShoe cover and hair coverWash hands regularly

Cleaning and Disinfection Cleaning and disinfecting the isolator at the beginning of each shiftCleaning and sanitizing the interior of the isolator between CSPs to avoid cross contaminationCleaning the background environment


Tools for Cleaning and DisinfectionWipers and Mops

– Polyester knit fabrics used for wipers and mop covers will not contaminate isolator. They are the best choice for “non-linting” and “non-shedding” materials.

– Wipers can be wetted with:–Detergents to clean/disinfect the isolator–Deionized water or 70% IPA to remove residual cleaning agents / disinfectants


Isolator Cleaning and DisinfectionCleaning

– Remove any residues and soils produced from the prior shift’s activity using small flat surface mops, wipers, swabs and detergents

Rinsing Following Cleaning– After cleaning, detergent residues are removed from the surfaces with wipers or

mops that have been wetted with sterile deionized water or sterile 70% IPA

Disinfection– The same procedures are followed for disinfection, except that liquid disinfecting

agents are substituted for detergents i.e. quaternary ammonium compounds (“quats”)


Isolator Cleaning and DisinfectionRinsing Following Disinfection

– After disinfection, disinfecting agent residues are removed from the surfaces with wipers or mops that have been wetted with sterile deionized water or sterile 70% IPA

Gaseous Sterilization– If required, the isolator can be sterilized with a suitable sterilant such as

Vaporized Hydrogen Peroxide (VHP)

Cleaning and Disinfection Between CSPsWipe the work surface of the isolator with 70% IPAPre-wetted wipers may be used, if availableGloved hands should be wiped to prevent cross contamination


Pre-Compounding ProceduresVerify the isolator was shut down by the previous user. The following record keeping processes can be utilized:

– Check list– Sign-off– PC log– Tagging

Check the gloves for any breach before starting because gloves are prone to wear.Wipe down the interior of the isolator.


Aseptic Compounding ProcessProper planning before the materials are placed into the isolator.Organize the necessary materials for compounding and placing them in the pass-thru. Wipe down surfaces of items.Allow pass-thru air to purge before the inner side door is opened.In order to maintain air cleanliness inside the chamber, the two doors should not be opened at the same time.Place items in the work zone and wipe down.Verify all items required for the compounding session are in the work zone.


Aseptic Compounding ProcessUse proper aseptic technique.Discard sharps in an approved sharp container after use.Remove completed products via the pass-thru.Label products before logging and delivery to patients.Compounding session is complete.

Post-Compounding ProceduresThoroughly sanitize the interior (refer to cleaning procedures) in order to prevent residual compounds from contaminating the next process.Shut down the isolator if desired.


Reference links

European Association of Hospitals Pharmacists– http://www.eahponline.org/

Pharmacy Practice News– http://www.pharmacypracticenews.com/

Clinical Pharmacy Europe– http://www.pharmacyeurope.net/

Hospital Pharmacy Europe– http://www.campden.com/default.asp?ptid=3&pid=2&pgid=1

http://www.eahponline.org/

http://www.pharmacypracticenews.com/



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Hospital Pharmacy Isolator Solutions for USP