New and improved cleaning

This paper highlights some of the recent developments in disinfectants and consumables and how they can be used successfully to improve the quality and capacity planning in life science cleanrooms.

It looks at three key areas :- - Improvements in a trigger spray system suitable for dispensing sterile product. - Since the control of bacterial spores is the major concern for most pharmaceutical companies there needs to be a continual development programme of safe and effective sporicides. - The demands placed on pharmaceutical cleanrooms for improved capacity planning, quality and process control mean that many companies now require pre-packed sterile components in formats tailored to their needs.

Improvements in a trigger spray system The method of application of a disinfectant or biocide is very important. The method used must be easy to use, cost effective to produce, expel the liquid in the required manner for cleanroom disinfection and perhaps most importantly protect the integrity of the contents throughout use. The two main systems of liquid application in a cleanroom environment are a trigger spray system or an aerosol can. There are benefits associated with a trigger spray system which include an adjustable nozzle so liquid can be dispensed as a jet or a spray enabling thorough wetting of the surface so that disinfection procedures are effective, they are environmentally friendly as they contain no propellants requiring special disposal procedures and all of the liquid can be dispensed from a trigger spray so there is no wastage making them a cost effective solution. However, there is a significant drawback with some trigger sprays as contaminated air can be drawn back into the bottle compromising the sterility of the liquid. By using the patented SteriShield Delivery System, this problem is resolved; providing a system with the benefits of a trigger spray whilst guaranteeing the integrity of the contents. The system operates as closed system preventing air being drawn back into the bottle; eliminating the possible chance of contamination of the liquid. It holds the liquid inside an ultra-clean, medical grade, polyolefin bag. The function of the bottle is simply to enclose and protect the bag in use. All points of entry into the bag including the dip-tube are completely sealed, thereby creating a closed system. This prevents any air being drawn back into the bag when the trigger mechanism is operated, unlike a normal spray bottle. In order to validate that the sterility of the liquid was not compromised during use, a series of tests à were carried out on one litre bottles filled with sterile liquid nutrient. Half the nutrient was sprayed out and the bottles left with their spray nozzles open in a class 10,000 cleanroom. Samples were removed at set time periods, double bagged and sent to an independent laboratory. The media was then tested to see if the contents had become contaminated. No growth was found in any of the samples demonstrating that a trigger spray fitted with the SteriShield Delivery System can protect the sterility of the contents for up to three months. Another consideration of the application of the disinfectant, within the cleanroom environment, is the use of alcohol to disinfect gloved hands on a regular basis, where the very use of the trigger spray itself could lead to contamination. This particular problem has lead to the development of a hands free dispenser that allows an operator to easily operate the trigger spray with their forearms or elbows preventing their hands from being contaminated. Systems exist which allow an aerosol spray to be used "hands free" however no equivalent systems have been available until now for trigger sprays.

Control of bacterial spores One of the most difficult requirements in a life science cleanroom is the control of bacterial spores. The main problem with spores is their resistance to many of the standard disinfectants that are used including alcohol. Often a successful sporicide will have other drawbacks as they can often be dangerous to humans or equipment or both. Hence the search for a non-hazardous but effective sporicide is very important. Traditionally used biocides such as alcohol, quaternary ammonium compounds, phenols and amphoteric surfactants are effective against bacteria in their vegetative state but useless against spores. Biocides that do have sporicidal activity including aldehydes, hypochlorites, hydrogen peroxide/peracetic acid are often toxic, irritant, corrosive, leave residues or need a long contact time. Sometimes these types of sporicides are withdrawn because of operator complaints, rusting equipment or health and safety issues. An alternative is an alcohol free biocide that has broad spectrum activity and excellent sporicidal action even under conditions of heavy soiling. The active ingredients are a mixture of a quaternary ammonium compound and stabilised chlorine dioxide. Premier Klercide-CR Biocide B is also non toxic, non irritant, non hazardous and non corrosive with a contact time of five minutes. Our development programme has looked at ways of improving the test methods for sporicides, as it is very difficult to get reliable results. Testing sporicides in the laboratory is very difficult for many reasons and can slow down the validation process. There is a draft CEN test method that proposes a log 3 reduction in spores but this is unlikely to be finalised for sometime. To overcome these issues we have a methodology available that is based on a membrane filtration method and is suitable for any disinfectant. The aim was to design a test that was reliable, repeatable at an independent laboratory and inexpensive to carry out. We used two laboratories to carry out the test to investigate two strengths of our product Premier Klercide-CR B and a peroxide/peracetic acid compound. á. The tests were carried out at 100% concentration in clean conditions and in soiled conditions at 90% of the ready to use concentrations. This is important to note, as the use of a ready to use concentration will always be diluted by the interfering substance and innoculum. The results were very consistent. We have several large pharmaceutical companies who are validating this test method for themselves with promising results. Many of the sporicides on the market are only available in liquid format either sprays, aerosols or dilutable powders so we have worked on the development of a sporicidal wipe. This is especially useful in very critical areas such as isolators and laminar flow cabinets that may have areas where liquid collects and then cannot easily be removed. Klerwipe-CR Sterile Biocide B impregnated wipes are specifically designed for cleanroom environments. The impregnated wipe is a low particulate polyester/cellulose blend that is suitable for use in cleanrooms up to ISO Class 5. This new sporicidal wipe gives operators more choice when it comes to controlling the risk of bacterial spores.

Increasing cleanroom capacity Other recent innovations have come in the area of pre-packed sterile consumables. There are many reasons for the need for sterile bulked bags of components.

- Busy units have stopped any non-core activities that used to include pre-packing of their own wipes and sterile components.

- Regulatory authorities are demanding better disinfection procedures usually leading to more physical wiping.

- Individually packed sterile components are often packed in unsuitable paper packaging that are prone to spore contamination and create excessive waste and particulate levels.

- The increased demand for better disinfection has resulted in high atmospheric levels of alcohol which in some instances has exceeded occupational exposure limits.

The need for better transfer and disinfection procedures has been highlighted by studies looking at the bioburden on a range of items passed into pharmaceutical isolators. This work published last year â showed that 60% of items ready for transfer into an isolator were contaminated with bacteria prior to disinfection. Of more significance the results showed that 40% were contaminated with bacillus spores, which would not be removed by spraying with alcohol alone. Hence, the reports recommendation of more wiping during transfer of sterile products. The answer to this problem is not to use individual sterile products, which then need wiping individually, but packs of multiple product. Klerpacks are a range of double bagged sterile multi-packs of syringes, needles etc, CE marked where required. The savings in time and money when using these multi-packs has lead to the range extending to include sterile pens, bins, waste bags, chemo dispense pins, fluid connectors, reconstitution devices amongst others. For users of gassing isolators the multi-packs can be provided in vaporised hydrogen peroxide proof packaging to reduce the aeration time and decrease production downtime. To conclude there are always areas within cleanroom disinfection and consumables where improvements can be made to products, testing and backup in order to make life easier for cleanroom operatives. We will continue to look for new areas where we can improve products and services, who knows what the next challenge will be?