1. GAMA Export Department SPORICIDAL WIPES

2. Product Overview Clostridium difficile Clinell Sporicidal – Format and Formulation Evaluation Studies Clinical Advantages/ USPs How we sell this wipe Issues & Questions (that commonly arise) Competing Products & UK regulations This presentation will cover the following topics: Presentation Layout

3. Currently patented in various countries and patent pending in other regions. Manufactured in China. Used by many hospitals in the UK – most notably by many University Hospitals in major cities. After 4 years of Research & Development, Clinell Sporicidal was released in January 2008 in the UK market. Product Overview

4. Wipes generate Peracetic acid which is well recognised as one of the most powerful antimicrobial agents available. The reason why Peracetic acid is not more commonly used is because it is very unstable – and this is the major drawback of this chemical compound. Our patent is based on the technology of keeping the Peracetic acid stable. Clinell Sporicidal is the most powerful wipe in the World to date. This is based on contact time and kill rate of spores. Product Overview

5. (Wipe Size: 21 x 30cm ) Clinell Sporicidal Wipes Wall mounted dispensers are available for this product.

6. Clinell Sporicidal is ideal for: Commodes Terminal cleaning All surfaces in suspected or proven Clostridium difficile cases. This product is marketed as a sporicidal wipe - not an everyday wipe - and has very specific uses. Clinell Sporicidal is used by over 60 NHS Hospitals in the UK. Product Overview

7. To be able to sell this product it would be advisable to have some knowledge of Clostridium difficile and this is outlined in the next few slides. This product is a specialised wipe that is used primarily to deal with Clostridium difficile or any other resistant bug causing outbreaks. Clostridium difficile

8. Gut flora consists of microorganisms that live in the digestive tracts and is the largest reservoir of human flora. Somewhere between 300 and 1,000 different species live in the gut. One of the functions of the gut flora is to prevent growth of harmful bacteria such as Clostridium difficile. This is a spore forming bacteria that is found in around 15% of the populations intestines and in this subgroup of people it is entirely harmless. It makes up part of the gut “flora” of microorganisms. A spore is a dormant non productive body formed by certain germs in response to adverse environmental conditions. Bacterial spores have thick walls and are very resistant to high temperatures, humidity, pH changes and disinfectants. Clostridium difficile

9. However there are cases then the Clostridium difficile (C.diff) can become overgrown in the gut and when this happens it becomes harmful to the patient as the bacteria releases toxins that can cause severe illness. This often occurs after the normal gut flora that controls the growth of C.diff is eradicated by use of multiple antibiotics. When stressed the C.diff produces spores which can tolerate extreme conditions that the active bacteria itself cannot tolerate. Clostridium difficile

10. Patients treated with broad spectrum antibiotics are at greatest risk of C. diff associated disease (CDAD). CDAD is the medical condition of being infected with C.diff. Other risks include: Patients are also at risk of developing C.diff when there are outbreaks in hospitals. Patients who are elderly Underlying illness that compromises the immune System / prolonged stay in a healthcare setting Recent gastrointestinal surgery Which Patients Get C.diff?

11. Transmission: Symptoms include: From person to person by the faecal-oral route. Because the bacteria can form heat resistant spores it can remain in the hospital environment for long periods of time. Once spores are ingested they pass through the stomach undamaged and can change to their active form in the colon and multiply. The bacteria can produce various toxins and these are responsible for the diarrhoea and inflammation seen in infected patients Diarrhoea Bloating Abdominal Pain Foul stool odour CDAD

12. Can range in severity. Can be life threatening and many deaths occur in the elderly population. Treatment is begun as soon as CDAD is suspected. Special antibiotics are used to treat CDAD. To highlight how important it is to deal with C.diff the total reported cases of CDAD in the UK in 2006 was 55,681 which is a rate of 2.45 cases per 1,000 bed days. With an average increased length of stay of 21 days, the cost of CDAD has been estimated at over £6,000 per case. Therefore the UK Government spent over £330 million a year to treat CDAD patients in 2006. CDAD: CDAD

13. 6,000 4,000 2,000 0 2001 2002 2003 2004 2005 2006 Underlying causeMentions Number of deaths Deaths from C.difficile Clostridium difficile 72% increase in deaths from 2005 to 2006

14. Deaths from C.difficile Clostridium difficile

15. In the UK the Department of Health released a list of interventions that they recommended for hospitals to follow to reduce the risk of CDAD and this came under the Saving Lives Guidelines. Prudent antibiotic prescribing hand hygiene Environmental decontamination (this is the important step regarding Clinell Sporicidal) Isolation/cohort nursing personal protective equipment They recommended the following interventions: UK Department of Health Guidelines for reducing C.diff infection

16. Prescribe antibiotics according to national guidance and local policy; minimise use of broad spectrum antimicrobials. Remember that using antibiotics increases the risk of C.diff growing unchecked in the gut. Review antimicrobial medication daily and stop as soon as possible. 1 Prudent antibiotic prescribing Percentage of Antibiotics Inappropriately Prescribed or Administered 50% Reasons for inappropriate antibiotic administration: Wrong dose Wrong drug Wrong duration Prevention of Spread of C.diff

17. Wash hands with soap and water before and after each contact with CDAD patient. In UK we have made hospitals conform to a campaign called ‘cleanyourhands’. 2 Correct hand hygiene Alcohol based hand rubs DO NOT kill spores so are not effective for hand hygiene. But washing hands with soap and water will physically remove the spores even though they wont be killed. By removing the biomass with the physical action of soap and water hand hygiene you can reduce the risk of hand transmission. Prevention of Spread of C.diff

18. This is the important step for Clinell Sporicidal. Implement enhanced cleaning in areas with CDAD patients. Reducing environmental contamination with Clostridium difficile spores will help reduce transmission. Ensure deep clean and decontamination of rooms after discharge of CDAD patients. 3 Environmental decontamination Prevention of Spread of C.diff

19. Always use disposable gloves and apron when handling body fluids and when caring for patients with CDAD. 4 Personal protective equipment Always use a single room if available. Cohort care for CDAD patients should be applied if single rooms are not available. 5 Isolation/cohort nursing Prevention of Spread of C.diff

20. Clinell Sporicidal only comes in packs of 25 dry wipes. In the pack it is completely stable and inactive, Before activation of wipe the user must wear gloves. Activation is by wetting the wipe with water under a tap or by dipping in a bucket. Wet for 2-3 seconds ensuring the entire non woven has been wetted and then squeeze all the water out before using. The pack does not have any special storage requirements but recommended to avoid very humid environments. Format

21. Clinell Sporicidal Wipes contains a safe, stable Peracetic acid generator, allowing Peracetic acid to be delivered in a quick, safe and easy to use system. Peracetic acid (PAA) has long been known to be one of the safest and most effective germ killers, but it has been notoriously difficult to keep in a stable format. Therefore in a pack of Clinell Sporicidal there is NO Peracetic acid - you only generate this when the wipe is activated The method of PAA stability is the patented technology part. Peracetic Acid (PAA)

22. Colourless liquid with a characteristic acetic acid (vinegar) type odour. Strong oxidising potential which is the kill method and this is a non-specific kill mechanism so no resistance to form with long term use. Oxidising agents act by oxidising the cell membrane of microorganisms which results in a loss of structure and leads to cell rupture and death. PAA is highly corrosive so the product has been formulated with chelating agents to stop this occurring. The pH is at 8-9 range. Peracetic Acid (PAA)

23. The hydrogen peroxide then reacts with the Tetra Acetyl Ethylene Diamine (TAED) to produce Peracetic acid. One of the powders is a glue which sticks the two non woven fabrics together and traps the powders in the middle. The wipe consists of 2 non-woven fabrics stuck together with different powders in the middle layer. The wipe is activated with water to initiate the production of hydrogen peroxide from the percarbonate peroxygen donor. How Clinell Sporicidal Works

24. The sporicidal activity benefits from the constant presence of both Peracetic acid and hydrogen peroxide in the wipe. Both are oxidising agents and kill spores. The non woven keeps the components apart until water is added. The powders that are layered between the 2 non wovens can be present in conditions that allow very rapid Peracetic acid generation. Powders and tablets of similar composition would not be stable which is what makes this product quite unique and is the basis for our patent. In other words without the non woven around the powders the concept would not work. Mechanism

25. Microbial load (cfu/g or cfu/ml) can be expressed as log10. cfu = colony forming units. So, if you have 100,000 microbes that is 5 log, 10,000 microbes is 4 log, 1,000 is 3 log, 100 microbes is 2 log 10 microbes is 1 log. Now, if you went from 100,000 microbes cfu/g to 10,000 microbes cfu/g that would be a 1 log reduction (5 - 4 log). Log reduction stands for a 10-fold or 90% reduction in numbers of recoverable bacteria. Therefore : 90% reduction is equivalent to a 1 log 10 reduction 99% reduction is equivalent to a 2 log 10 reduction 99.9% reduction is a equivalent to 3 log 10 reduction 99.9999% reduction is equivalent to a 6 log 10 reduction Log Reductions

26. Clinell Sporicidal was tested at various independent UK accredited laboratories including The Hospital Infection Research Laboratory in Birmingham (this is the most renowned laboratory in the UK). Clinell Sporicidal showed a sporicidal kill count of greater than log 6 within 1 minute contact times under dirty conditions. Evaluation

27. The European Standard test for spores is called prEN13704 but the contact time to pass this test is 60 minutes and the kill count needed to pass is only 3 log. Contact time means “wet” contact time between the disinfectant and the microorganism. It is very unlikely that a surface could be wiped and be expected to remain wet for 60 minutes and therefore this test is impractical in reality. Therefore Clinell Sporicidal was tested under a different protocol using a test designed by Babb JR which requires a greater than 6 log reduction in clean and dirty conditions within a 5 minute contact time. In comparative terms this is 7,500 times (multiplication factor) more powerful then achieving a 3 log reduction and 60 times faster as well. Clinell Sporicidal achieved a 6.75 log kill count within 1 minute contact time in dirty conditions. Sporicidal Testing

28. Started using Clinell Sporicidal in January 2008 Compared CDI rates with chlorine versus Clinell Sporicidal. Published in The Nursing Times, 2011. Research conducted by Jean Yves Maillard. Comparing sporicides in wipe format. Published in the American Journal of Infection Control, 2011. Clinical Studies

29. This paper was published in September 2011 and describes the impact of introducing Clinell Sporicidal wipes into the environmental cleaning regimen of an acute NHS Trust to reduce Clostridium difficile infection (CDI) rates. As part of a ‘bundled’ approach to infection prevention and control measures, the wipes were introduced separately from other interventions. Over previous years, CDI rates had fluctuated, but remained relatively constant. One year after the introduction of Clinell Sporicidal Wipes the CDI rates reduced by 72%. Royal Free Hospital Medical School Royal Free Hospital Study

30. 4 3 2 1 0 2006/7 2007/8 2008/9 Mean C.difficile Rate C.Difficile Rate per 100 Patients 2.71 3.13 0.88 Royal Free Hospital Study

31. All interventions listed by the Saving Lives guidelines were implemented into the hospitals decontamination policy for several years. C.diff rates dropped but stayed at around the 300 cases per year average for several years. The hospital infection control department decided to switch their chlorine to Clinell Sporicidal in the hope that compliance would be increased. After one year the rate of CDAD has dropped by 72% and the following year the rate was even lower. This paper also commented on the savings the hospital made by reducing their CDI rates. Royal Free Hospital Study

32. Dr Jean-Yves Maillard, Welsh School of Pharmacy Cardiff University has a very well renowned microbiology department and there has been some research conducted into Clinell Sporicidal and other “sporicidal” wipes by Dr Jean-Yves Maillard who has been looking at all sporicidal wipes and their effects on C.diff on surfaces. He spent over a year looking at the many different sporicidal wipes on the market to understand what the alternatives are to liquid sporicides and what role they may play in reducing Clostridium difficile infection rates. This landmark study was published in The American Journal of Infection Control in April 2011. Clinell Sporicidal was proven to be the most effective sporicidal wipe on the market. Cardiff University Study

33. Wipes Ingredients disclosed in label and claim Claim on label Inorganic peroxygen generator, tetra acetyl ethylenediamine, surfactants Wipe A (Clinell Sporicidal) Sporicidal Wipe B (Tuffie5) <1% polymeric biguanide hypochloride, alkyl di-methyl benzyl ammonium chloride, didecyl dimethyl ammonium chloride Sporicidal Wipe C (NewGenn)QAC, PHMB and bronopol Bactericidal claim & claim against Clostridium difficile on label Wipe D (TriGene)Didecyl dimethyl ammonium chloride 0.45% Sporicidal Wipe E (AzoMax) Composition not disclosed; “effective against C. difficile spores under 30 seconds with mechanical action of cleaning” Sporicidal Wipe F (PDI Rapid) Didecyl ammonium chloride, lauralkonium chloride, polyaminoporopyl biguanide, 2-bromo-2-nitro-para1-3-diol Sporicidal Wipe G (Active8) “impregnated with low-level biocides” 5% cationic surfactant, amphoteric surfactant and EDTA Sporicidal Wipe H (SuperNova) Composition not disclosed Sporicidal Wipe J (Enduro) <1% cationic and non-ionic surfactantsNo sporicidal claim on label Cardiff University Study

34. Efficacy testing.The study looked at 3 different properties of the sporicidal wipes: Bacterial removal How good are the wipes in removing Microbial contaminants? (not killing effect) Bacterial transfer “adpression tests” Can the wipes transfer survivors to other Surfaces (i.e. cross-contaminate)? Antimicrobial activity Can the wipes kill the bacteria they remove? Step 1 Step 2 Step 3 Cardiff University Study

35. Sporicidal Effect (against C.difficile 20291 ribotype 027) Sporicidal effect (log10 reduction ±SD) 10 s contact time 5 min contact time Unmedicated wipe0.14 (± 0.07)+0.42 (± 0.07) Hypochlorite soaked wipe+0.50 (± 0.83)4.64 (± 0.00) Wipe A (Clinell Sporicidal)0.72 (± 0.32)3.74 (± 2.26) Wipe B (Tuffie 5 Wipes)+ 2.38 (± 0.03)+0.05(± 0.10) Wipe C (NewGenn Wipes)+ 1.55 (± 0.09)+0.11 (± 0.10) Wipe D (TriGene Advance Wipes)+ 1.90 (± 0.23)+0.20 (± 0.04) Wipe E (AzoMaxActive Wipes)+ 1.20 (± 0.05)+0.26 (± 0.08) Wipe F (sani-Cloth Rapid Wipes)+ 0.28 (± 0.10)+0.41 (± 0.20) Wipe G (Active8 Wipes)+ 1.02 (± 0.41)+0.32 (± 0.04) Wipe H (SuperNova Wipes)0.01 (± 0.14)+0.30 (± 0.05) Wipe J (Enduro Patient Wipes)+ 0.17 (± 0.32)+0.12 (± 0.08)

36. Efficacy testing against C.difficile. Bacterial removal Only Clinell Sporicidal (Wipe A) removed over 4 log of spores. Chlorine soaked wipes were the next highest at 2 log removal. Bacterial transfer “adpression tests” Clinell Sporicidal was the only wipe to not transfer spores from one surface to the next. Antimicrobial activity No wipe showed a sporicidal kill effect at 10 seconds contact time. At 5 minutes contact time only Clinell Sporicidal Wipes and Chlorine soaked wipes showed a kill effect. Step 1 Step 2 Step 3 Cardiff University Study

37. Main conclusions are that Clinell Sporicidal Wipes are the best at removing spores and not transferring them as compared to any other wipe with a sporicidal claim including chlorine soaked wipes. With regard transfer of spores, the same material as Clinell Sporicidal was used without the chemicals to see if transfer is prevented and this was not the case. It is concluded therefore that the chemical composition within the wipes are responsible for the non-transferance of the spores. Not possible to achieve a sporicidal kill effect within a very short contact time with any wipe product (this includes 5,000ppm of chlorine). Clinell Sporicidal was the only branded wipe proven to be sporicidal at a 5 minute contact time. Cardiff University Study

38. It has a number of very specific uses: Clinell Sporicidal is primarily a chlorine replacement Commode cleaning Suspected & confirmed sporicidal outbreaks Terminal cleaning Uses of Clinell Sporicidal

39. Quick and easy to use Environmentally friendly No toxic fumes No measuring or dilutions needed as with chlorine agents – which is complex to mix and is very often mixed incorrectly. Very little training needed – anyone can use it without error. Breaks down to harmless by-products of vinegar, carbon dioxide and water and poses no risk to the user, the patient or the environment. No persistent toxic or carcinogenic residuals are formed unlike chlorine (hypochlorite) based products. Can be used in close proximity to patients unlike high concentration hypochlorite based products ensuring no risk of lung damage. Advantages Over Chlorine

40. Works in highly soiled conditions Unlike chlorine based products, PAA will penetrate dirt and organic matter and kill spores within faeces. Chlorine based products will not do this without detergent and therefore Peracetic acid has much better kill rates in dirty conditions. Clinell Sporicidal has detergent incorporated into the wipe so no first line of cleaning is required separately Advantages Over Chlorine

41. It is not an everyday wipe and it has very specific uses. This is the most powerful wipe in the world and its primary function is to kill spores. GAMA hasn’t created a new chemical but has devised a technology of keeping one of the best antimicrobial agents stable. PAA has been used on endoscopes for many years. Many leading UK University Hospitals are using this product and have reduced their C.diff rates dramatically. The Royal Free Hospital is attempting to publish their findings on this in the next few months. There are a number of key points to mention: > > > How to Sell this Wipe

42. Clinell Sporicidal hasn’t just passed prEN13704 but has also passed the Babb et al test which requires a 100 times more powerful effect at a 12 times faster speed to pass. NOTE: prEN13704 is a preliminary test and not fully approved yet hence the prefix “pr” before the test number. However on comparison with products that claim to pass EN13704, Clinell Sporicidal has been shown to have a 7,500 times more powerful kill count as well as a 60 times faster contact time. Outline advantages over chlorine and emphasise the danger of using chlorine regularly. Make a point of saying that this safer easier to use product will increase compliance and the subsequent drop in CDAD rates will save the money. > > > How to Sell this Wipe

43. Q What happens if someone uses it without wearing gloves? The worst case scenario is a superficial epidermatitis (skin inflammation) which may cause tingling of the skin and possible transient skin blanching (temporary colour change). Most people do not have any reaction to the wipes (around 80% will not react). If a reaction does occur then it usually passes within a few minutes and is not dangerous at all. Advise to wash with copious amounts of water. Issues and Questions

44. Q Is this a COSHH (Control of Substances hazardous to health) product and is PAA dangerous to use? We need to pass this through our Health and Safety officer. PAA usually is considered a COSHH product but this is usually for PAA at much higher concentrations then the 3000ppm that this product generates. PAA is not dangerous to use at 3000ppm which is 0.3%. In addition the PAA has been stabilised with pH modifying agents within our formulation to optimise the antimicrobial activity by keeping it within a tight pH range (range 8-9.5) and at its most stable pH. Chelating agents are present to stop divalent metal ions destabilising the PAA Issues and Questions

45. > This product is much more expensive then chlorine and I don’t think the hospital can afford it. Clinell Sporicidal will always be more expensive then chlorine but the advantages it offers over chlorine are very important to highlight. By having an easier to use product that is safe will increase staff compliance which will in turn reduce C.diff rates. By reducing C.diff rates this allows for a cost saving for the hospital. This product will also save on nursing time and provide staff and patients with a safer disinfectant. Finally, this product is safe to use on surfaces and medical equipment unlike chlorine which means no spend on replacing damaged items. Issues and Questions

46. > We are looking at various other sporicidal products before deciding what to do. This will be a good time to talk about the different sporicidal wipes on the market and explain the differences between them and Clinell Sporicidal. Most are fairly new and include products like PDI Rapid Wipes, Tuffie 5, Azomax Active, Newgenn wipes, Supernova as well as a few others. There are a number of major differences between what we are offering hospitals and the above list of products. It is very important to highlight to the customer the difference between Clinell Sporicidal and other competing products which are outlined on the following slide. > (Continued) Issues and Questions

47. > Point out the following facts: We are the only sporicidal product to tested at an accredited laboratory. Clinell Sporicidal are the only wipes to show a contact time of 1 minute and a kill count of greater then 6 log. The other companies will not openly tell hospitals that their contact times are 60 minutes with a 3 log kill count (EN13704). A contact time of 60 minutes is not achievable in practice as no surface would stay wet for that long. A contact time of 1 minute for Clinell Sporicidal is very practical and achievable in a clinical setting. We have also conducted comparison testing on many of these other wipes and have found that many of them are not sporicidal at all i.e. they fail EN13704 regardless of its impractical application. This data is available on request. Most sporicidal wipes contain quaternary ammonium compounds as the active ingredient and this is well documented as not being sporicidal. Published data is available on request. > > > > Issues and Questions

48. Difficult to do a cost analysis on this product in the usual way as this is not an everyday wipe and doesn’t replace existing wipes as such. 1 2 3 Chlorine is much cheaper to use but the arguments must be put across on the benefits of using this over chlorine and the potential for cost saving with reduction of CDAD. This product should be looked at as new advanced technology which justifies the premium price tag. Cost Analysis

49. This is due to its ease of use which will lead to better staff compliance. 4 5 6 Also our product has been shown to be more effective in dirty conditions on comparison with chlorine. Just 1 case of C.diff that is prevented will save a UK hospital approximately £6,000 and this cost saving will more then make up for the increased spend on Clinell Sporicidal. The only effective way to approach procurement and justify cost is to explain to them that this product will reduce their C.diff rates to a higher and more effective way then chlorine ever would. Cost Analysis

50. There are many wipe products currently on the market claiming to be sporicidal. The last year in particular has seen a rapid increase in sporicidal products on the market in the UK and these have been released by some of the big market players such as PDI, Synergy Healthcare and Verna Care. However, all these products are Quaternary Ammonium based and are renowned for giving false positive results on spore testing. Most microbiologists do not consider them to be effective against spores. Competitor Products

51. No agency monitors what companies are doing and what tests they need to pass and which laboratories they do their testing at. Generally left to hospitals to look at every product themselves and in many cases they do not know what to look for anyway. Currently UK rules on disinfectants and their uses is extremely lax and unlike other countries who have more stringent regulations in place. UK Disinfectant Regulations

52. It is possible to get false positive results for spore testing with quaternary ammonium formulas. The reason for this is that QACs are highly charged molecules and therefore can stick to the spore surface without actually killing the spore. Then when the spore opens (germinates) the quaternary ammonium that has stuck to the surface can have some effect on the bacteria inside the spore. Poor laboratories can sometimes not tell the difference between the actual spore being killed versus the spore opening and the bacteria inside being killed. Companies often use unaccredited laboratories who cannot pick up on this type of problem and this can have a major effect on the results. Additional Notes

53. Questions? GAMA Healthcare Ltd. International Sales Department Unit 2, The Exchange Brent Cross Gardens London NW4 3RJ England, United Kingdom.