Pharmaceutical clean rooms: specialty hygiene coatings

Clean rooms are areas in which it is essential that microorganisms are not allowed to proliferate because they could contaminate pharmaceuticals and directly affect human health.

The infrastructures being coated are diverse, creating demands on a coating to cope with anything from old, possibly damp substrates, to modern synthetic surfaces. They must also allow for moisture vapour pressure, give excellent adhesion even if steam-cleaned daily, be resistant to cleaning chemicals or contamination from chemical splashing and continue to provide a seamless film-protected environment.

To ensure this, the coatings must be part of a system approach that recognizes substrates — particularly old, previously uncoated ones — will be contaminated with microorganisms and require sterilizing before a hygiene system is applied. Following this, the specific situation may demand that the coating can be reinforced to resist impact damage and that a fully seamless approach is provided over existing or potential joints and cracks.

Industry requires the system to give long-term protection from microorganism growth and this will usually be seen as the main requirement. A further requirement is that the coating system will do this without exuding contaminating chemicals. If biocides, which leach to the surface, are used to protect the film, they will be short-lived and will potentially contaminate the environment.

There are additional specialty requirements. Pharmaceutical industries demand clean rooms whose surface finishes will not attract and retain dust, and are easily cleaned. Rooms can be prone to condensation and this emphasizes the point that film-protective agents must be nonleaching.

Table 1 Properties of hygiene topcoats for different applications.

Time restraints mean a room must be ready to be used 24–48 hours after the application of a hygiene coating. To comply with this, water-borne agents are best as they can be applied without contaminating the environment with high levels of volatile organic compounds (VOCs).

Legislation

Manufacturers will have in-house demands from their own hygienists and environmental managers, and external legislation regarding validation and performance of hygiene measures. When considering what legislation prevails at a given time, we truly enter a field for experts. A simple look at some relevant extracts from the European Directive (93/43/EEC) is useful:

"Surfaces must be maintained in a sound condition and they must be easy to clean and, where necessary, disinfect. This will require the use of impervious, non-absorbent, washable and non-toxic materials, and require a smooth surface up to a height appropriate for the operations."

The European Biocidal Products Directive demands that any biocide or product containing a biocide, such as a hygiene coating, shall be subject to regulation. Most European countries have adopted this position.

Finally, VOC regulations are decisive. It is highly desirable to use water-borne coatings, which have as low a content of VOCs as possible.

Pretreatments and coating systems

What coating systems are available? What are the key benefits and properties, and what advantages are there over conventional paints?

Coating systems. The choice is often made from remarkably few criteria:

• Is the system perceived as safe to use and does it carry any approvals to verify efficiency?

• Has the system been validated to recognized standards by an independent third party?

• Can it be used in the given process area?

• Is the system a complete package?

• Can it be applied by brush, roller or spray as may be convenient or dictated by process considerations?

The package approach is important to guarantee the coordination of the system, and should include the following products:

Repair mortars. One- or two-pack materials based on the most modern liquid or spray-dried polymers in conjunction with cement and microsilica technology.

Sealants. Specific water-based acrylic sealants are available. These are internally film protected in a similar way to the coatings, in sealing around door/window frames, and between coatings and skirting boards, for example.

Biocidal washes. Typically a biocidal wash is water-based and supplied as a concentrate for use as-is in known areas of contamination, or diluted with water as a sterilizing wash.

Primers. Water-borne primers are available to provide the functions of substrate binder (where friable), for metal primer and to ensure top coats strongly adhere.

Top coats. These may be used alone, in combination with each other as defined by the manufacturer or as part of a reinforced system. Table 1 shows details of five types of top coats, all water-borne with low-VOC levels, fire retardancy and defined physical test data. In most cases, two coats can be applied in a day.

Figure 1 Procedure for producing smooth crack-bridging finish.

These features allow a full range of substrates to be coated, though some demand a system approach rather than any single coating. For example, a tailor-made system would include lining board substrate, which incorporates

• primer to kill suction and prevent absorption of the coating resin binder into the substrate, thereby ensuring film integrity

• product A set with glass-fibre woven reinforcement

• two finish coats of product B.

This gives a tough impact-resistant system, which covers the joints in between the boards to give the required seamless finish.

Other reinforcements include knitted nylon reinforcement tapes for specific joint treatments, which may be used locally as shown in Figure 1 — in this case the crack could be static or dynamic.

Hygiene coatings versus traditional materials. Traditional materials include conventional fungicidal paints, tiles and wall cladding systems.

Conventional fungicidal paints. These are designed to 'quick kill' microorganisms with biocides that are in excess on the surface of the dried paint. The drawback is that they leach potentially toxic chemicals into the environment.

Figure 2 Construction of a seamless hygiene cladding system.

Ceramic tiles. Grouting is the weak link with growths usually seen in that area. They can only be used on ideal substrates.

Wall cladding systems. These are inert, but expensive and require specialist installation. They do not provide a seamless finish and usually have no inherent 'surface protection', unlike hygiene coatings. However, they can be used as the basis of a seamless system (Figure 2).

Microbial problems and hygiene coatings

Pharmaceuticals and clean rooms. The threat here is from the contamination of products and cultures from (mainly) airborne bacteria. Equally, it would be disastrous to have fungal/mould growth giving potential cross-contamination. It requires only low levels of opportunist pathogens such as salmonella and pseudomonas to cause spoilage.

Figure 3 Changes in bacterial count over time (arbitrary units, bacterial count 3106).

Combating the proliferation of microorganisms. What is needed from a hygiene coating to prevent proliferation and how is this achieved? A comparison on a life cycle graph illustrates the point in Figure 3. On the unprotected film, bacteria proliferate until, in the closed test system, they run out of space and food. The contact/quick kill paint swiftly kills bacteria until the active runs out and growth recommences. The correctly formulated hygiene coating shows a growth pattern as it neutralizes more slowly, but then eliminates growth to virtually zero proliferation.

Any individual organism must be neutralized by a process that is nonsite specific (for example, multisite) to avoid the risk of resistance developing. This can be simply summarized as:

Mode of action. The biocide chemically disrupts the metabolism of the microorganisms preventing life processes.

Sites of action: Respiration; spore forming; protein/enzyme synthesis; reproduction; and energy assimilation. All these are sites or areas where the reproduction processes are attacked and this results in a neutralized microorganism by the following process:

• surface is contaminated

• assimilation at multisites

• disruption by biocide

• denatured

• nonproliferating, nonsporing.

The biocide is thereby absorbed at multisites and the microorganism is rendered neutralized and unable to reproduce. Because of the multisite action, resistance to attack does not develop.

The mode of action of the coatings illustrated in this article can be summarized as follows (Table 1):

Product A. This consists of a polymer-rich binder with a low-film PVC. The active ingredient(s) are distributed throughout the dominant binder, held in place by a chemical modifier action forming a crystal structure associated, on coalescing and drying, with the acrylate bond structure. It will, therefore, remain evenly distributed and will not migrate or accumulate at the surface. The biocidal action — more correctly described as a biostatic action — relies on an active ingredient of extremely low solubility. The microorganism will, however, solubilize the active at a molecular level. This is absorbed into the cell across the cell wall/membrane. As this is nonsite specific, there is almost no chance of a build up of resistance.

Products B–E. These rely on different in-film protectives but with the following common properties:

• nonmetallic antimicrobial dispersion

• low water solubility

• bound and evenly distributed throughout the film — therefore, consistent lifetime activity

• surface active — adsorbs into the cell a minute amount of active in solution at the surface, which is enough to render the cell nonviable

• chemically disrupts the cell by preventing basic life processes

• main pathway — nuclear cell diffusion

• can disrupt a number of stages of this process.

A more detailed scientific explanation of the mode of neutralization of microorganisms (fungi and bacteria) by hygiene coatings is set out in Table 2.

Approvals and test certification

The hygiene coatings illustrated in this article have been tested to a variety of challenge tests from European sources.

Fungi/yeasts. The recognized test in the UK is BS3900 Part G6 "Anti-microbial Surface Properties". This calls for resistance testing to a minimum of nine mixed fungal/yeast inoculum. More can be tested. Product A in this paper was subject to a mix of 39 species, successfully neutralizing all.

Table 2 Mechanisms by which hygiene systems neutralize fungi and bacteria.

Bacteria. The search for a universally accepted test method continues in this area. There have been several attempts by the International Biodegradation Research Group to produce both a European and an ISO standard method. Current thinking centres on the Japanese Standard JIS Z2801, which is a surface antimicrobial challenge test. Hygiene coatings act as a secondary line of defence to known cleaning regimes. Tests are also commonly performed on a wide range of additional bacteria.

Key points

Conclusion

A holistic approach is needed to select a hygiene coating for the pharmaceutical industry. The coating must offer a range of physical properties to perform a number of associated tasks dictated by both the substrate onto which it is being applied, as well as the use environment with decorative aspects being covered by a range of matt to gloss finishes. The antimicrobial 'film protected' coating must be demonstrated to be multisite specific in its action, as safe as possible to use and offer guaranteed long-life performance.

Robert Stanfield is technical director of Liquid Plastics Ltd, UK.