The success of any pharmaceutical construction project may ultimately depend not so much on the process and services provisions which can be evaluated objectively against defined performance specifications but on the perceived ‘quality’ of the facility based on a subjective evaluation of the finishes. For this reason attention to the selection of materials and the detail of their assembly or application must assume a high priority for the designer.
It is also important in considering structural solutions for a project that in addition to the obvious requirement for suitability, allowance is made for the significant services loads often imposed in a pharmaceutical application. The structure should permit frequent penetration for holes and chases. Care should be taken in design of floor slabs particularly in the location of movement joints to ensure they do not compromise the integrity of applied floor finishes.
Construction Techniques
Choice of construction techniques is influenced by a number of external factors, in addition to the obvious requirements that they be fit for the purpose chosen and do not, of themselves, contribute to the particulate burden. The key factors are: • Facility location
• Flexibility
• Cost effective solutions.
Facility location: The location of a facility can influence construction materials,
not only in terms of availability of raw materials and installation skills, but also by strict interpretation of building codes.
Flexibility: Once particulate contamination performance criteria have been satisfied,
and these must not be compromised, flexibility is the greatest single requirement facing facility managers. How to design a facility which meets current performance requirements, can be adapted to accommodate frequent equipment changes and can be upgraded to meet developing standards without requiring total refurbishment.
Cost effective solutions: With so many diverse requirements to be satisfied, a
thorough value engineering exercise is required at the detail design stage to ensure that the proposed solutions represent best value per currency unit.
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Primary Construction Materials
With such a wide variety of construction materials and systems available, it has already been suggested that selection can be a matter of personal preference and available budget. Clearly some guidelines can be established to assist selection.
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The philosophy must be to provide a room fabric which has the following characteristics:
• Hard, impervious, smooth surfaces with no sharp angles or edges, in order to prevent particle generation.
• Coved corners, angles and plinths to facilitate thorough cleaning.
• Smooth, flush details to abutments with openings or the interface of different materials so as not to inhibit air circulation.
Generally, design guides refer to these elements as ‘crack and crevice free construction’. Selection of materials will also be influenced by local building codes and in many cases by corporate standards of construction. In the former case, requirements for structural stability or fire resistance and the ability of materials to resist surface spread of flame will be of particular importance.
Corporate standards reflect many years of experience in detailing construction to meet the manufacturing demands of particular product requirement and, invariably, provide cost effective solutions. They form an invaluable starting point for any design exercise.
Externally elevational treatment will be subject to local planning consent and will either reinforce corporate identity or enclose space as economically as possible depending on client policy. We are not so much concerned here with these subjective values but with looking objectively at production spaces within these buildings.
There are essentially three methods of internal wall construction: • Masonry construction
• Lightweight construction (Figure 7.6) • Demountable partitions (Figure 7.7).
The two former methods require applied finishes if they are to meet performance standards, while the latter will generally be prefinished. Most in situ construction techniques require the application of a finishing material if the construction is to satisfy design guide criteria. As room cleanliness levels increase or where process demands dictate, so the sophistication of the finishing coat will also increase.
At the lowest end of the scale, this may be as straightforward as water-based vinyl emulsion type paints, applied directly onto fairfaced masonry or gypsum board. The comparative frequency of maintenance can be readily offset by low cost and ease of application.
A considerable range of hard wearing epoxy and similar resin-based paints and spray coatings are available, suitable for the most demanding aseptic applications. Many such products possess an inherent elasticity which resists cracking, even when movement of the substrate induces tension.
Flexible sheet vinyl materials, either 1 mm or 2 mm flooring grade, are often used in aseptic rooms of the highest quality. The vinyl is carried over preformed cove formers at wall/wall and wall/ceiling junctions to ensure easy cleaning. The use of high quality impact adhesives ensures that, even in negative pressure environments, the material stays firmly fixed to the wall. All joints are thermally welded ensuring a smooth, impervious wall surface.
Personal preference may permit the use of other materials. Rigid sheet materials of acrylic and similar substances can, with careful detailing of joints, also provide attractive and hard wearing surfaces. Ceramic tiles, both glazed and unglazed, have
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been used extensively in the past although their use has declined with the advent of epoxy materials with similar wearing characteristics. The breakdown of grouted joints in more aggressive cleaning environments has made this type of finish extremely suspect.
As with walls, ceiling construction falls into quite distinct categories:
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Figure 7.8 Stainless steel floor gully (details courtesy of BM Stainless Steel Drains Ltd)
• Monolithic systems • Tile and panel systems.
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Figure 7.9 Shield detail in vinyl skirting
the cleanrooms, the space above the ceiling becomes an important service zone. Only rarely therefore, will the concrete soffit of a roof or intermediate floor slab be finished as a ceiling. It is much more likely that a ceiling system will be suspended well below such elements, to facilitate service distribution.
Selection of floor finishes will be influenced by local conditions more than any other materials. Of particular importance is the presence of wet processes. Standing water on floors can be a significant problem. Wear characteristics may also be significant if other than pedestrian use is anticipated. Wheeled vehicles, particularly pallet trucks and similar wheeled units, can have a devastating effect on floor
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materials. In addition to care with selection, detailing is also important with expansion joints, drain outlets (Figure 7.8), wall/floor coved junctions (Figures 7.9 and 7.10) and other material interfaces requiring particular attention.
Materials fall into distinct groupings: • Sheet and flexible tile materials • In situ and tile terrazzo
• Floor coating systems: epoxies, paints and seals.
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Secondary Elements
Doors serve two principal functions in cleanroom facilities: firstly to permit the passage of people and secondly to permit movement of materials, either in small quantities by hand and trolley, or in bulk by pallet truck etc. The two functions place quite different requirements on door systems. As cleanliness levels increase, the need to restrict movement in order to reduce the contamination burden assumes increasing significance.
Personnel doors will range from standard painted timber or steel doors in low grade rooms, through solid timber doors which have plastic laminate faces and are edged with hardwood, metal or plastic laminate (Figure 7.11). Doors sets purpose made for higher grade pharmaceutical applications are available in GRP, stainless steel and glass (Figure 7.12). The essential in selecting doors, as with other finishing materials, is the maintenance of hard wearing, crack free surfaces. Attention must be paid to detail design in locating frames into structural openings. Selection of
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iron-mongery is also important. Closers must work smoothly, often against considerable room overpressure.
It is essential to avoid the use of unnecessary locks and latches in favour of pull handles and push plates. Electromagnetic interlocks, which minimize the penetrations of the door skin, should be used where possible. Additional protection may be necessary on door faces susceptible to damage from truck and trolley movement.
Perhaps because early cleanroom legislation discouraged the use of windows or because satisfactory detailing was difficult to achieve, cleanrooms were, for many years, claustrophobic areas with no natural daylight. There are, however, significant operational benefits from the extensive use of glazing. These might include: • Greater unity between different sections of the manufacturing process.
• Supervision without the necessity for supervising staff to be continuously entering and leaving the cleanroom through a complex changing process.
• Improved working environment for production operators.
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• Greater aesthetic interest.
Glass is, in fact, an extremely suitable material for cleanroom use, as it readily satisfies the principal design criteria, being hard, smooth, impervious and easily cleanable. It can be used effectively in conventional pane sizes (Figure 7.13) or by using thicker, laminated panels for entire full height partitions.
It is therefore important that every effort is made to overcome the technical difficulties, such as contaminated air ingress around frames and solar heat gain. Whenever possible, glazed areas should be flush with adjoining wall surfaces and double glazed, to meet this criteria, on both sides of the wall where the cleanrooms adjoin one another. Glass should be located into purpose made frames in stainless steel or similar materials or located directly into appertures formed in the wall construction using silicone mastic adhesive/sealants.
Material transfers, speech membranes and even conveyor pass throughs can be located with great ease.
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A wide range of fixtures and fittings are essential within the room, if the manufacturing function is to be effective. It is not possible to cover every eventuality, but the list is certain to include:
• Light fixtures
• Filter housings and return air grilles (Figure 7.14) • Material transfer hatches
• Piped and electrical services (Figure 7.15) • Autoclaves, production equipment, etc.
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The same considerations given to other aspects of cleanroom detailing will also apply to these components. Wherever practical, fixtures must be flush mounted and sealed into the room fabric. Non-essential equipment should be located outside the room, allowing routine maintenance to be effective without any requirement for maintenance staff to enter the cleanroom, or for the integrity of the room to be breached. Fluorescent light tubes and even HEPA filters can be changed in this way, should service access above the rooms be practical. Where this access is not possible and tubes or filters are changed from inside the room, fixtures must be detailed to ensure that removing diffusers does not breach the room integrity, permitting ingress of contamination.
Long horizontal service runs should also be avoided whenever practical. The zone above the suspended ceiling provides an ideal area for installing service ring mains from where individual services can drop directly to points of use. Services can be grouped and brought into the cleanroom through service pendants. Hollow wall construction may also permit flush mounting of services which would otherwise be an untidy intrusion of the room.
Detailing may be as specific to applications as is function. It is therefore very difficult to provide details which can be regarded as generic or typical.
A significant range of materials and details have been considered here. It is important in concluding to restate the point that production areas must be ‘fit for purpose’. It is not suggested for one moment that all processes need to be conducted in rooms that are also suitable for aseptic manipulation. The selection of appropriate materials and construction techniques for differing applications requires the designer to establish a balance between cost and risk: risk that materials may break down and contaminate the manufacturing process and control of project cost within a realistic budget. Establishing this balance and applying similar consideration to development of layouts based on a thorough understanding of manufacturing process and utility requirements are essential contributions to be made by the design team towards the creation of a GMP manufacturing facility.