MANUFACTURING Article Busting the myths of CHLORINE DISINFECTION A successful cleanroom disinfectant needs to meet many criteria, not only in terms of its efficaciousness but also in terms of packaging, ease of use, operator acceptability, etc. Many articles have been written on how to specify and select a cleanroom disinfectant, but this is not the main focus of this article. However, a brief summary of requirements helps when comparing available chlorine chemistries. The ideal cleanroom disinfectant decontamination process is if the Taking as a given good broad spectrum disinfectant has no residue that needs to efficacy including highly resistant be removed or as a minimum is free bacterial spores, the requirements for rinsing. the ideal cleanroom disinfectant are The product will need to have in quite lengthy: a sterile option for grade A excess of a 12-month unopened shelflife and B environments1, non-flammable so and in excess of a three-month in-use it can be used over large areas with no shelflife to be practical to store and use. health and safety concerns, also fast This ideal disinfectant would then need drying with short contact times to reduce to be manufactured to the requirements the time taken for biodecontamination. of cGMP, be notified to the BPR2 and However, in an ideal world, this cannot provided in cleanroom compatible be traded for any problems with either packaging in a variety of formats so it equipment or operators and the wider was suitable for use in all areas of the environment in terms of disposal. cleanroom. It goes without saying that Another requirement shortening the this all needs to be achieved in a cost- effective formulation. Many people believe that this ideal sporicide ABOUT THE AUTHOR: does not exist and a Karen Rossington, compromise must always be made. hypochlorite known as chloride of lime. in the 1930s and today it is the most Marketing Consultant to On first reflection, a chlorine- John Snow used it in 18543, after an widely used of all the chlorinated Contec Inc. based disinfectant would not outbreak of cholera to attempt to bleaches. Rossington works as necessarily spring to mind as disinfect the Broad Street pump water Hypochlorite solutions were used for an independent the disinfectant that meets all of supply in London. Claude-Louis the treatment of open wounds during consultant to these ideal needs. Sodium Berthollet, in 1785, prepared a bleaching World War I and led to the use of onsite companies in the hypochlorite is the most widely agent by dissolving Scheele’s gas in generation of hypochlorite in hospitals. pharmaceutical used chlorine-based surface water and in 1789 improved it by mixing These disappeared out of favour until contamination control disinfectant but has some it with a solution of caustic potash the 1990s, which saw a great surge in sector. She represents known drawbacks, notably (KOH); this was carried out in a French the interest of onsite generation of Contec Inc., a manufacturer of inactivation in organic matter, corrosive chemical plant in Javel and was known chlorine. These onsite generators contamination control products for to some metals and it will leave a and remains known today as Javelle provide a solution containing only 0.8% lifescience cleanrooms. Having particulate residue. However, all chlorine water. A short while later, Antoine- chlorine, which is non-hazardous, previously worked with isolator and disinfectants are not the same. Germain Labarraque replaced the however hazardous hydrogen gas is cleanroom design, Rossington has Advances in production methodologies expensive potassium hydroxide with produced as a by-product. Onsite spent the last 14 years in both the have allowed the creation of a caustic soda, resulting in what was generation is also quite inefficient marketing and development of disinfectant that meets all of the probably the first use of sodium compared with bulk production because cleanroom disinfectants and has aforementioned requirements. hypochlorite as bleach. of associated electricity costs. written and presented many papers Chlorine first began to be used as a Dry calcium hypochlorite appeared on on cleanroom disinfection and History of chlorine disinfection disinfectant in the late 1800s, early the US market in 1928. This bleaching biodecontamination. One of the first known uses of chlorine 1900s. Liquid bleach, sodium agent contains up to 70% active chlorine for disinfection was in the form of hypochlorite, came into widespread use and is also known as high-test EPM 36 MANUFACTURING Article Efficacy data for 2,000 ppm hypochlorous acid. hypochlorite (HTH). It is available in a dissociated hypochlorite ion (OCl-) variety of forms including powder, predominates at higher pH values, granules, briquettes and tablets. Calcium above 7.5 pH, whilst the undissociated hypochlorite systems tend to be used for hypochlorous acid (HOCl) predominates small water treatment plants and well at lower pH values. At pH 5, nearly all systems. Calcium hypochlorite has a the chlorine is present as HOCl, while a very strong oxidising potential and pH value of 10 drives nearly all the consequently is very dangerous to store chlorine to be present as OCl-. and use. Calcium hypochlorite dissolved in water generates 2 mols of hypochlorous acid for every 1 mol of calcium hypochlorite. Chlorine as a disinfectant Not all chlorine species are equally effective as disinfectants. Many studies have explored the mechanism of chlorine disinfection and although it is not possible to precisely explain how Fig 1. At low pH and high chlorine each particular chlorine species works, concentrations, the hydrolysis is not complete 4 current theory states that inactivation and a significant fraction remains in the form occurs by means of one or more of the of molecular chlorine Cl2. following mechanisms: inactivation of the key enzymes, disruption of nucleic In a sodium hypochlorite solution that acids rendering them non-functional and normally sits at a pH of 11–13, all oxidative damage to cell walls or other available chlorine is in a form of vital cell components. For each of the hypochlorite ions, which as previously mechanisms described above, the discussed is far less efficacious than effectiveness of each disinfecting agent hypochlorous acid. Until recently, it has is a function of both its rate of diffusion not been possible to create through the cell wall and its reactivity hypochlorous acid in a stable solution with the cell wall, proteins and nucleic with a usable shelflife. Hypochlorous acid. acid generated from dissolving dry Hypochlorous acid (HOCL) is the most calcium hypochlorite has a shelflife of effective disinfectant in the chlorine approximately four hours and therefore family available in dilute solution. It is has not been suitable for use in suggested that HOCL is 80 to 120 times5 pharmaceutical or healthcare more efficacious than sodium environments. Advances in chlorine hypochlorite. Owing to the fact that chemistry have made it possible for HOCL has no charge and has a contamination control products relatively low molecular weight, it is manufacturer Contec Inc. to stabilise a better than the other chlorine-based solution based on calcium hypochlorite disinfectants at penetrating the cell walls. at a pH of 3.5 to 5.5, so all available It also reacts more rapidly than other chlorine is in the form of hypochlorous chlorine-based disinfectants to oxidation acid as a ready-to-use product with a reactions with organic matter, i.e. the shelflife of 18 months. critical components of microbial cells. Conversely, the hypochlorite ion is a Stabilised hypochlorous acid efficacy relatively poor disinfectant because of its If the science was correct, this inability to diffuse through the cell wall. hypochlorous acid-based disinfectant Since it is negatively charged, it is should be more efficacious and faster electrostatically repelled from the cell acting than the equivalent sodium walls, which are also negatively charged. hypochlorite product. Contec’s solution It is much larger in size than an HOCL of 2,000 ppm hypochlorous acid was molecule so it also diffuses more slowly. therefore tested against the standard EN panel of tests for disinfectant efficacy; Chlorine chemistry the table (top of page) shows a Chlorine is added to water in one of summary of these results. Complete kill consideration. Hypochlorous acid at low References three forms: elemental chlorine (chlorine against spores was achieved in both concentrations is non-hazardous and 1EudraLex. The Rules Governing gas), sodium hypochlorite solution or clean and dirty conditions against a requires no specialised disposal process Medicinal Products in the European Union calcium hypochlorite powder (high-test modified EN 13697 surface test in 1 min. or operators to wear any PPE other than Volume 4 EU Guidelines to Good hypochlorite). Chlorine gas reacts This is a significant increase in both log standard cleanroom gloves. Manufacturing Practices for Medicinal rapidly with water to form two reduction achieved and kill rate over Very often, fast-acting and efficacious Products for Human and Veterinary Use. compounds: hypochlorous acid (HOCl) sodium hypochlorite. Various micro- sporicides are detrimental to the Annexe 1. and hydrochloric acid (HCl). organisms were tested, including a environment they are used in. At 2EU Biocides Regulation (528/2012). particular resistant concentrations of 2,000 ppm, 3White’s Handbook of Chlorination and house isolate, which hypochlorous acid is non-corrosive, so Alternative Disinfectants, Black and was typed as P. when used in a controlled manner will Veatech Corporation, Wiley Publishing. glucanolyticus. Test be compatible with cleanroom materials. 4GM Fair, et al. The dynamics of water work was also Although not residue free, as chlorination, Journal of the New England repeated against the hypochlorous acid does leave a very low Water Works Association, 1947 61 HOCl is a weak acid that further newest version of EN 16506 for fungi and level of calcium salt on the surface — 285–391.