Slide 1 © PharmOut 2017

Good Cleanroom Design & Construction Practice

Presented by Gordon Farquharson

July 2017

Slide 2 © PharmOut 2017

Agenda

Good Design & Construction Practice – Cleanrooms

• Based on the scope and intents of the revised edition of ISO 14644-4 “Design, Construction & Start-up” due in 2018.

• ISO Link to Annex 15 of the PIC/S GMP Guide.

• Some new energy saving considerations.

• Practical tips – the devil is in the details.

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ISO 14644-4 :2001 and NEW 2018

2001

• Adequate space.

• Specify ISO cleanliness class.

• Clean construction protocol.

• Avoid cracks, crevices, and uncleanable areas.

• Impervious, non-shedding surfaces.

• Coved junctions.

• Guidance on air changes/hr for non-UDF.

• Design review and testing fits with old Annex 15.

2018 new aspects

• Generally updated.

• Air change rates guidance removed; source strength of contaminants and ventilation effectiveness principles included.

• Energy saving measures identified.

• URS added to link to new Annex 15 PIC/S GMP guide.

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Every Cleanroom is a “Prototype” !!

• Process & Product has unique features

• The host building and its environment are unique

• The equipment configuration and layout is unique

• The project team is unique

BUTAll cleanrooms use common components and techniques

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Cleanrooms are very different!

Cleanroom technology

applied to API manufacture

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Cleanrooms are very different !

Formulation equipment

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Role of the Cleanroom 1

1. Exclusion of the external environment.

2. To create the class of cleanliness and environmental conditions required for the process by dilution or displacement of the contamination generated.

• To maintain ISO cleanliness Classes (1-9), or GMP Grades (A-D).

3. Containment of hazards arising from the process.

4. Control of Process-to-Process cross-contamination. A Pharma GMP issue.

5. Control and management of Material & Personnel flows and procedures by way of planning and layout of the suite.

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Configuration of Clean Rooms

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Design Layout

The expectation however, is quite clear. The layout and planning should ensure the following:

1. Effective segregation between the external environment and the classified space.

2. Well managed materials and personnel flow.

3. Segregation spaces of different grade or class.

Planning and layout requirements are not defined in GMPs or Cleanroom standards.

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Don’t Underestimate the Impact of the Process Equipment

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vacuum

heatingcooling

CIP/SIP

classified area

uncontrolled area

uncontrolled area

The Potential of Closed Process Equipment

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Designing for Adaptability

Loose fit - enables changes with minimum disruption

Consider modular design

Clean construction protocol ISO 14644-4

External access for maintenance

Service chases

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Corridors and Working Spaces

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Remember Maintenance of Technical Systems

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Some images from MRC Systems & Clestra

Construction of clean rooms

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Basic Construction Methods

Finish options:

• Sheet PVC

• Sprayed elastomeric paint

• Epoxy paint

Masonry + gypsum applied plaster +

applied finish

Finish options:

• Sheet PVC

• Sprayed elastomeric paint

• Epoxy paint

Gypsum or calcium silicate board +

closing of joints + applied finish

• Mild steel painted

• Stainless steel

• GRP – Glass reinforced polyester

• Phenolic sheet

Options

GMP doesn’t mandate any specific approach.

1. “Stick-built”. In-situ construction

2. Pre-fabricated, pre-finished cleanroom wall & ceiling panel systems

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Choosing the Preferred Option

• Shouldn’t always be at the top of the list.

• Remember you should be considering >20 years life.

Cost

• Materials

• Labour to install

• Technical support

Local sourcing

• Clean/dirty - Dry/wet

Construction environment

• Have to make decisions early for pre-fabricated

• Have longer to cogitate for stick-built

Project lead times and decision making

• Is the systems compatible with development and evolution of the business operations?

Modification and relocation requirements

• In house / Local resources

• Vendor dependent

Repair

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Other Attributes of The Construction System

Ceiling:• Suspended• Bridging on walls• Walk-on

Low level return air ducts:• In wall construction• Double wall required• Plant on surface

Services in walls:• In wall thickness• In a service pod on wall• In a service chase

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Masonry System

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• Masonry walls

• Concrete ceiling

• Hard plaster (gypsum)

• Door frames set into

the wall structure

• Applied epoxy paint to

walls

• Thin epoxy floor finish

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Gypsum Board and Frame System

• Metal frame

• Calcium silicate or Gypsum board attached

• Joints taped

• Finish applied – this case a glass reinforced polyester resin.

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GRP Cleanroom Panel SystemPicture courtesy of MRC Systems Ltd

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Typical Metal Panel System

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Floor Channels...

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Ceiling Channels...

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Walk-on Ceiling…

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Single or Double Glazing…

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Doors Swing Slide Powered…

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Requirements - Door Attributes

1. Swing doors should close with air pressure.

2. Often need to work with electromechanical interlock systems

3. Doors should be self closing (soft close to avoid pressure shocks).

4. Hygienic design. Avoid cavities and ledges.

5. Powered doors

• Becoming more common

• Ensures optimum open/close rate

• Can help avoid hand contact

6. Sliding doors

• OK

• Ensure cleanroom style

• Avoid floor tracks

• Ensure top track cleanable

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Door Options

• Hinged

• Horizontal sliding

• Vertical roller door

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Advantages of Sliding Doors

• Saves space (in particular in clean corridors for Grade C & D areas).

• No wind effect when opening & closing.

• More convenient for moving materials & equipment (pallets, IBCs).

• Less susceptible to mechanical damage.

• More convenient for large openings.

• Can be part opened.

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Disadvantages of Sliding Doors

• Sometimes greater cost than double leaf swing door.

• Top track needs periodic inspection.

• Not good for dusty rooms – should be on clean corridor side.

© FactoryTalk 2015 10-May-15

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Doors in OSD Application-With Airlock

+

+++

Process Room

+

Clean process corridor ++

+++

Process Room

+

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Doors in OSD Application – Without Airlock

34

Process Room

+

Clean process corridor ++

Process Room

+

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Sliding Doors in OSD Cleanroom

Example MSD Singapore

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Sliding Door Details

Very important to choose specialist good supplier.

Essential Top track, door leaf, and bottom guide.

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Single Door Width

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Insulated Sliding Doors – Cold Room

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GRP Sliding Doors

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Glass & Low Leakage Sliding Doors

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Door Leakage

• Generally some leakage is OK.

• Should be estimated and allowed for.

• If cleanrooms are too airtight, pressure balancing and pressure stability become problematic.

• Example – SP 30 +/-3 Pa

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Cleanroom Flooring (1)

• PVC sheet (lowest cost)

– Adhered to floor.

– Seams welded

– Cove former to walls

• Tacky mats

– Permanent

– Peel-off

Sheet materials adhered to floor:

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Cleanroom Flooring (2)

1. Epoxy (thin self levelling)

• Available in ESD/static dissipative and conductive versions.

2. Polyurethane (thin self levelling)

• Some uses the natural power of silver to fight bacteria, and

• Available in ESD/static dissipative and conductive versions.

3. Epoxy terrazzo (thick)

• recycled granular material.

4. Tiles

• Ceramic (chemical plants)

• Epoxy

• Terrazzo

Applied screeds

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Cleanroom Flooring (3)

1. Classified cleanrooms

• Surface swabbing with mops and controlled disinfectant materials.

• Routine hygiene and cleanliness monitoring

2. Non-sterile manufacturing

• Machine cleaning preferred

• Periodic housekeeping controls.

Cleaning

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Equipment Integration

• Space for the equipment.

• Integration with the room fabric.

• Maintenance access.

• Room Pressure barriers.

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Equipment Integration

• Room Pressure barriers.

• Impact of equipment on room pressure due to air in-flow (loss) into the equipment.

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Thank you for your time.Questions?

Gordon Farquharson

gordon.farquharson@pharmout.net

www.pharmout.net

Executive Consultant