CLEANROOMTECHNOLOGY.COM

THE INTERNATIONAL JOURNAL OF CONTAMINATION CONTROLJuly 2014

CONTAINMENT:New isolator designs for the scale-up oftissue regeneration in the lab

SINGLE-USE SYSTEMS:Single-use containment systems offercost-effective solution for pharma

FOOD TESTING:New developments mean fasterdetection and greater automation

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To evaluate whether cleanrooms arethe best method of protecting today’sproducts and operators in setenvironmental conditions, one mustconsider the cleanroom classifications.Cleanrooms are classified according to thenumber and size of particles permitted pervolume of air (see Figure 1). For a typicalcleanroom, the relevant particle size is0.5µm and this is directly related to thebacterial contamination levels. Along withthe classifications come the requirementsfor hypergeometric distribution sampling,utilities consumption and cleaning thathas to be both validated and repeatable.

Cleanroom technology sets out tominimise particulates and maintain setenvironmental conditions – but why notconsider the alternative, containmenttechnology?

Containment, barrier isolation andisolator (or glovebox) technologies are allbased on the same basic method ofenclosing an environment. TheInternational Society for PharmaceuticalEngineering (ISPE) defines containmenttechnology as a ‘leak-tight enclosuredesigned to protect operators fromhazardous or potent processes or protectprocesses from people or detrimentalexternal environments or both.’

A basic containment system consists of:a solid cabinet, usually 316L stainlesssteel; viewing window; gloves and gloveport assemblies; supply and exhaust withmicrobially retentive filtration system(high-efficiency particulate air (HEPA)minimum); input and output openings(equipment-door airlocks, rapid transferports) etc. and various other penetrations;extract that provides a negativeenvironment for operator protection; andbuilt-in safety features.

There are two types of isolators asdefined by the ISPE – closed or open. Inthis article closed isolators will be thefocus as they represent the bestalternative solution to cleanrooms (seeFigure 2).

In comparison with a cleanroom, theadvantages of such a closed type ofenclosure are numerous (see panel onnext page). Overall, the benefits ofcontainment technology provide asuperior sterility assurance and costsavings. With the trend towards higherpotency and purity of pharmaceutical andbiopharmaceutical compounds,containment technology is becoming thenorm. Because operators need to limittheir exposure to these products, handlingoperations must be carried out inside theisolator.

Containment technology has changed

vastly over the past five years and thesesystems can accommodate integratedequipment, providing set environmentsand operator and product protection for avery competitive investment (see Figure 3).

With cleanroom technology, everyelement has to be cleaned and disinfected,including HEPA filters which are the mostcomplicated components to cleanand maintain their integrity.Cleanroom cleaning operationstraditionally consist of wipingdown and moppingwalls and flooring,which can takehours to complete.By usingcontainmenttechnology, clean-in-place (CIP) orsteam-in-place

(SIP) operations are fully automated andthe operator only has to push a button torun a full wash-in-place cycle. The systemcan spray one or multiple detergents thatprovide a set cleaning recipe for each typeof compound processed for repeatableoperation.

Cleanrooms have long provided environmental control foroperations or tasks where the products need protection, butMichelle Frisch, PSL, asks are they the best choice for today’srequirements of cleanliness and limited operator interference?

July 2014 23CONTAINMENT

Figure 2 (above): Highcontainment isolatorfully enclosed withlower and upperchambers fordispensing andsampling operations

FIGURE 1: ISO 14644 CLASSIFICATION TABLEMaximum Number of Particles in Air

ISO Class(particles in each cubic metre equal to or greater than the specified size)

Particle size

> 0.1µm > 0.2µm > 0.3µm > 0.5µm > 1µm > 5µm

ISO Class 1 10 2

ISO Class 2 100 24 10 4

ISO Class 3 1000 237 102 35 8

ISO Class 4 10,000 2,370 1,020 352 83

ISO Class 5 100,000 23,700 10,200 3,520 832 29

ISO Class 6 1,000,000 237,000 102,000 35,200 8,320 293

ISO Class 7 352,000 83,200 2930

ISO Class 8 3,520,000 832,000 29,300

ISO Class 9 35,200,000 8,320,000 293,000

ARE CLEANROOMSAN OBSOLETETECHNOLOGY?

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CONTAINMENT

The cleaning time for a typical isolatorcan be less than an hour, depending onthe size of the unit, representing a hugetime- and cost-saving.

Cleanroom technology requires 95%confidence that the classification requiredhas been achieved. With an isolator orglovebox, containment is guaranteed andcan be proven as it is normally monitoredand proven with a particle counter atqualification. The classification can thenbe validated and maintained over time asit is repeatable.

The utility consumption is vastlydifferent between a cleanroom and anisolator. An isolator, being typicallysmaller, uses less energy to operate andbecause it can be operated by onlycompressed air,eliminates anyelectrical consumption.Furthermore, anotherconsumption reductionis achieved with HVACsystems, in thatisolators have reducedflow rates comparedwith cleanrooms, andthey can be vented directly

into the atmosphere.Some systems caneven re-circulate upto 99% of air ornitrogen, greatlyreducing utilitiesconsumption.Thereforecontainmenttechnology consumesfar less energy tomaintain the setenvironmental

conditions than acleanroom.

Figure 4: This dual isolator for highcontainment and aseptic processes has acompact and mobile design with low utilityconsumption

Using glovebox technology eliminatesany possible operator contamination ofthe compound or process, as the operatornever has direct contact with the product.This is one of the main advantages of suchsystems as human interaction is the mostdifficult parameter to control.

Recently, major improvements havebeen made in containment technologies.Containment systems such as isolatorsand gloveboxes can be more and morepolyvalent, circulating air or nitrogen andworking under negative or positivepressures. Such advanced technologiesallow the use of a single, compact andmobile isolator to integrate a full asepticfilling line for potent materials, forexample. The product is thereforeprotected from bacterial agents, theoperator and environment remain safeand operating costs are lower thancleanroom facilities (see Figure 4).

So why would anyone consider puttingin a large, energy-consuming, cleanroomthat is complex to clean and maintainwhen one can achieve betterenvironmental control and reduceoperating costs with a smaller, moreeffective footprint?

CONTACTSMichelle Frisch MBA, Sr. Manager, Global Technical SystemsPowder Systems Limited (PSL)Estuary Business ParkLiverpool L24 8RG, UKT+44 151 448 7700info@powdersystems.comwww.powdersystems.com

Figure 3: Fully integrated clinical trial productionline within high containment isolators, installedon site

1. Achieving set environmental conditions that are repeatable and easy to control, such as relative humidity (RH) control with set points, as well as setting and maintaining oxygen levels

2. Achieving lower ISO Class than cleanrooms with a containment down to the nanogramrange or a non-detectable level – thanks to pre-filtered air or nitrogen, HEPA pre-filtration and air pressure differential

3. Easy cleaning within a small area and no floor to wash; simple to validate as operations are repeatable. Isolator systems allow the use of solvents for cleaning and can be sterilised to reduce any bacterial contamination

4. Reduced cross-contamination and the removal of operators within the same environment as the materials

5. It is more effective and ergonomic to contain the operation rather than wrapping the operator in suits and head covers, while handling products and instrumentations easily through glove ports

6 Improved operator safety by removing the operator from the environment in which operations such as filling occur

7. Fully automated system to control all utilities and environmental conditions8. Lower capital expenditure with a greatly reduced footprint and in many cases

containment technology has a lower capital outlay compared with buying and installing a cleanroom

9. Up to 35–50% lower energy costs because the reduced space that isolators require means smaller air flow capabilities are needed, which in turn leads to lower utility consumption

10. Overall lower operating costs with less maintenance but also reduced or even eliminated gowning and de-gowning time

Benefits of containment technology

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