Confidential - May Not Be Reproduced, Distributed Or Disclosed Without Prior Consent from Teleflex EMEA Athlone

Clinical Evaluation CR0026 Transurethral (Malaysia) Rev AF

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Confidential

CLINICAL EVALUATION REPORT CR0026

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Table Of Contents

1. Introduction and Executive Summary ...... 3 2. Intended Use ...... 3 3. Contraindications ...... 4 4. DeviceConfidential Classification ...... 4 5. Device Description...... 5 6. Product Experience / Post Market Data - 2015 Review……………………………..13 7. Product Experience / Post Market Data – 2013 review ...... 15 8. Product Experience / Post Market Data – 2010 review ...... 29 9. Risk Analysis / Review ...... 51 10. PubMed Database search strategy results ...... 51 11. Product Literature and Instructions For Use ...... 52 12. Device Equivalency ...... 52 a. Clinical Parameters ...... 52 b. Technical Parameters ...... 52 c. Biological Parameters ...... 53 13. Market experience data ...... 53 14. Author Objectivity ...... 53 15. Post Market Clinical Follow Up ...... 53 16. Summary and Conclusion ...... 53 17. References ...... 55 18. Appendices; Appendix 1. Authors CVs ...... 59 19. Appendix 2. Device Codes ...... 62 20. Approvals ...... 63

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1. Introduction and Executive Summary Teleflex Medical actively updates its risk documentation with post market surveillance information. As part of this process, the medical device clinical evaluation is updated. The evaluation is used to assist in determining if:

• ConfidentialAny previously unrecognised hazards or hazardous situations are present?

• Any estimated risk(s) arising from a hazardous situation have been rendered unacceptable?

This clinical evaluation includes data obtained from the post-market surveillance phase for the device, including, data obtained from the use of the device and available literature.

The devices classified as Transurethral Devices belong to the risk Class IIa, Is per the Medical Devices Directive 93/42/EEC as amended by 2007/47/EC and are well established in medical practice. The report also considers products sold in the US.

This report presents a critical evaluation of a compilation of data relating to the clinical use, safety, performance, design characteristics and intended purpose of Transurethral Devices (Appendix 2).

The potential hazards and hazardous situations associated with the use of transurethral devices were reviewed. The clinical risks were estimated. This clinical evaluation report demonstrates that these devices are suitable for their intended purpose and confirms that any undesirable side effects are outweighed by the clinical benefits of these devices.

The data provided in this clinical evaluation report supports the following conclusions

. under normal conditions of use (defined in the Instructions for Use), Transurethral devices achieve their intended performance, and . the risks associated with the intended use of these devices are acceptable when weighed against the benefits to the patient

2. Intended Use The Hyperthermia bladder 2 way 100% silicone catheters are intended for routine or post operative drainage of the bladder.

The 2 or 3 way soft simplastic balloon catheters (Foley) are intended for routine transurethral drainage or for routine post operative routine transurethral drainage and irrigation of the bladder.

The 2 or 3 way simplastic balloon catheters (Foley) are intended for routine transurethral drainage or for routine post operative routine transurethral drainage and irrigation of the bladder.

The catheterization set is intended for preparation of patient for urological catheterisation.

The latex Foley catheter catheters are indicated for routine transurethral drainage of the bladder or for routine post-operative transurethral drainage and irrigation of the bladder.

The Nelaton Type Catheter is intended for Intermittent Self Catheterisation (ISC).

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The pre-connected drainage system with latex Foley catheters are indicated for routine transurethral drainage of the bladder.

The pre-filled syringe is intended to be used as filling medium for urological catheter balloon.

The PVCConfidential catheter product is intended for intermittent catheterization.

The saline water sachet is used as an accessory for delivery of contents in coating activation (such as hydrophilic, etc).

The Ureteral connector is intended for connecting catheter to drainage bag.

The GentleCathTM kit is intended for intermittent urinary catheterization and is for single use only.

76200 Catheter insertion kit is intended for intermittent urinary catheterization and is for single use only.

The 2 Way All Silicone Catheter for Radiological Display is used for the introduction of contrast media into the urethra and bladder drainage.

3. Contraindications The pre-connected drainage system with latex Foley catheters: Latex allergy, insurmountable obstruction of the urethra.

Latex Foley catheters: Some balloon catheters from the Rusch range contain latex and consequently should not under any circumstances be used in patients with latex allergy. Where urethral passages cannot be negotiated, transurethral catheterisation should not be undertaken.

PVC intermittent catheter with water sachet: Urethral stenosis, urethral obstructions, urethral infections and acute urinary tract infections

The 2 or 3 way soft simplastic balloon catheters (Foley): The Rusch soft simplistic balloon catheters contain latex and consequently should not under any circumstances be used in patients with latex allergy. Where urethral passages cannot be negotiated, transurethral catheterisation should not be undertaken.

The 2 or 3 way simplastic balloon catheters (Foley): The Rusch simplastic balloon catheters contain latex and consequently should not under any circumstances be used in patients with latex allergy. Where urethral passages cannot be negotiated, transurethral catheterisation should not be undertaken.

4. Device Classification The device classifications per Annex IX of the Medical Device Directive 94/32/EEC as amended by 2007/47/EC are shown in Table 1:

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Table 1: Transurethral Device Classification per the Medical Device Directive 94/32/EEC as amended by 2007/47/EC Class Rule HyperthermiaConfidential bladder 2 way IIa 5 100% silicone catheter 2 way simplastic catheter IIa 5 3 way simplastic catheter IIa 5 Catheterisation Set IIa 5 2 Way and 3 Way Latex Foley IIa 5 catheter Nelaton type catheter Is 5 Preconnected drainage IIa 5 system with latex Foley catheter Prefilled syringe Is 1 PVC Catheter with saline Is 5 water sachet Saline water sachet Is 1 Ureteral connector IIa 2 2 Way all Silicone Radiological IIa 5 Display Catheter

The GentleCath insertion kit is a Class II device (FDA). The 76200 Catheter insertion kit is a Class II device (FDA).

5. Device Description The following table describes the transurethral devices.

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Rusch Amber Latex Silicone or Paediatric (6-10), Paediatric (approx. Paediatric (3 or Cylindrical 2 opposed 2 Way Latex PTFE Adult male (12-30), 30), 5), eyes Foley Adult Female (12-22) Adult male (approx. Adult male, (5 catheter1 40), or 30), Adult female Adult female (approx. 25) (5)

Silasil Plus 2 Latex Silicone Paediatric (6-10), Paediatric (approx. Paediatric (3), Cylindrical, Single or 2 Way latex Adult male (12-30) 30), Adult male, (5 Tiemann or opposed Foley catheter Adult male (approx. or 30) Coude eyes 40)

1 Some devices are provided with either a stylet or a prefilled sterile water syringe.

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Rusch Gold 3 Latex Silicone Paediatric (6-10), Paediatric (approx. Paediatric (3), Cylindrical, Vertically Way latex Adult male (12-30) 30), Adult male, (5 whistle or opposed Foley catheter Adult male (approx. or 30) round tip eyes, 40) diametricall y opposed eyes Rusch Amber Latex Silicone Adult male (12-30) Approximately 40 Adult male, (5 Cylindrical 2 opposed 3 Way latex or 30) eyes or Foley catheter staggered eye Silasil Plus Latex Silicone Adult male (12-30) Approximately 40 5 or 30 Cylindrical 2 opposed Blue 3 Way eyes or latex Foley staggered catheter eye

Rusch Gold 3 Latex Silicone Adult male (12-30) Approximately 40 30 Round, Staggered Way whistle or eye / hematuria couvelaire vertically latex Foley opposed catheter eyes

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Jacques Latex Non coated 8-18 Approximately 40 N/A Nelaton 2 opposed Nelaton eyes catheter No balloon

Robinson Latex Non coated 8-30 Approximately 40 N/A Nelaton Staggered catheter eyes No balloon

All purpose Latex Non coated 8-30 Approximately 40 N/A Nelaton or 2 opposed catheter cm open tip eyes No balloon

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PVC Riplex PVC Non coated 8-36 Approximately 20, N/A Clear Staggered catheter 40, 76 moulded tip eyes No balloon

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Table 2: The name, material, surface coating/treatment, charriere size, length, balloon volume, catheter tip and catheter eyes of the Transurethral devices Device Name Material – Surface Ch. size available Length (cm) Balloon Catheter Tip Catheter shaft and coating/ volume (ml) eyes balloon treatment Flocath PVC Hydrogel Paediaric (6-10), Paediaric approx. N/A Nelaton, olive Staggered hydrogel Adult male (8-18), (30), or Tiemann eyes No balloon Adult female (8-16) Adult male approx. tip (40), Adult female approx. (20) Flocath Plus PVC Hydrogel 10-14 Approximately 20, N/A Nelaton or Staggered 40 Tiemann tip eyes or No balloon double staggered eyes Rusch PVC Hydrogel 6-16 Approximately 20, N/A Nelaton or Staggered intermittent 40 Tiemann tip eyes or catheter No balloon double (Coated staggered Flocath) eyes Flocath Quick PVC Hydrogel 8-20 Approximately 20, N/A Nelaton tip Staggered (with saline 40 eyes water sachet) No balloon

Flocath PVC Lubragel 8-18 Approximately 20, N/A Nelaton, olive Staggered Introgel 30, 40 or Tiemann eyes or No balloon tip double staggered eyes

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Table 2: The name, material, surface coating/treatment, charriere size, length, balloon volume, catheter tip and catheter eyes of the Transurethral devices Device Name Material – Surface Ch. size available Length (cm) Balloon Catheter Tip Catheter shaft and coating/ volume (ml) eyes balloon treatment 2 Way PVC Non coated 12-28 Male approximately 10 or 30 Cylindrical, 2 opposed simplistic 36.5 coude, eyes, catheter Tiemann, staggered Couvellaire eyes or single eye 2 Way soft PVC Non coated 12-28 Male approximately 10, 30, 75 Cylindrical, 2 opposed simplastic 42 coude, eyes, catheter Tiemann, staggered Couvellaire, eyes or whistle single eye Dufour 3 Way PVC Non coated 18-24 Male approximately 30 or 75 Cylindrical, Vertically simplastic 36.5 whistle, opposed catheter dufour, eyes/ Pengelly staggered eyes 3 Way soft PVC Non coated 16-24 Male approximately 30 or 75 Coude, Vertically simplastic 42 whistle, opposed catheter dufour, eyes / couvellaire staggered eyes, 2 opposed eyes, 3 Way soft PVC Hydrogel 16-24 Male approximately 30 or 75 Coude, 2 opposed simplastic plus 42 dufour, eyes, catheter couvellaire staggered eyes

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The GentleCath Kit contains an under pad, a pair of gloves (large), lubricating jelly, an antiseptic (benzalkonium chloride) wipe and a urine bag

GentleCath Kit ComponentConfidential Description Under pad: Blue, 3 layer paper and film laminated with embossed pattern, approximate dimensions: 18” x 13.5” +/- 0.5”

Gloves: Powder-Free (Strata) Vinyl Gloves, size large, wrapped in protective paper

Lubricating jelly: Glycerin based hydrogel from Aplicare 3g of sterile lubricating jelly in a sealed foil pouch

Antiseptic wipe: 0.13% Benzalkonium Chloride impregnated wipe in a sealed poly-foil pouch NDC 44019-323-01 (Mfg: Shanghai Yinjing Medical Supplies Co. Ltd)

Urine collection bag: Medical Grade Polyvinylchloride (PVC) extruded film bag with print, a PVC tube and a PP connector

Film band Translucent PE (Polyethylene)

The 76200 kit ((FDA ProCode KOD and FCM) consists of Walleted Vinyl gloves, Underpad, PE collection bag, BZK wipe and Urine drainage bag.

6. Product Experience / Post Market Data - 2015 Review

The objective of this review is to evaluate clinical data for transurethral devices and/ or clinical data for equivalent devices. This review focuses on the addition of the 2 Way – All silicone Radiological Display Catheter. The 2 Way All Silicone Catheter for Radiological Display is developed for the radiology visualization of diverticula’s of the female urethra by means of retrograde Urethrograph. The instrument consists of a three-lumen silicone catheter with a taper that can be pushed over the shaft. One lumen serves to drain the bladder, one lumen serves to fill the balloon and the third lumen, which is fitted with a 2-way stopcock, serves to apply the contrasting agent.

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6.1 Safety and Effectiveness, comparison to predicate device:

A comparison of the device characteristics for devices for which clinical data is available in the published clinical literature 2 Way – All Silicone RÜSCH BRILLIANT Madduri Radiological Display Urethrogram ConfidentialCatheter Catheter Teleflex Medical Teleflex Medical Cook Medical Device Name Catheter for Radiographic RÜSCH BRILLIANT Madduri Urethrogram Visualisation of the Foley Catheter Catheter Female Urethra Catheter Silicone Silicone Silicone Material – Shaft and Balloon Catheter Approx. 41 cm Approx. 41 cm 37 Lengths (cm) Catheter Size 14 12-24 14 (Ch.) Balloon 10 10 5 Volume (ml) Catheter Tip Cylindrical Cylindrical - Catheter Eyes 2 opposed eyes 2 opposed eyes - Surface Non-coated - - Coating/ Treatment

CR0071 provides clinical data on the safety and performance of a Rüsch 3-way Silicone Foley catheter. Rusch Balloon Catheters made of silicone, Bladder Drainage Catheters, Foley Type are intended for routine post-operative transurethral drainage and irrigation of the bladder.

There are several devices on the market equivalent to the Teleflex Medical Urethral devices. BARD markets the 3 way Foley catheter and ranges from sizes Ch. 16 to Ch. 26, balloon volume 5ml to 75ml. Cook Medical markets the Universa® 2-way Silicone Foley balloon catheter, which ranges from 6 to 26 Fr and 25 cm and 34 cm length and with round tip. The balloon volume ranges from 1.5, 3, 5 and 30 ml. The device is sterilised using ethylene oxide. Bard Medical markets the BARDEX LUBRICATH 2 way Foley balloon (3ml and 5ml) catheter (4, 8 to 30 Fr.). Bard Medical also markets a polyurethane urethral catheter from 4 to 6 Fr. Covidien markets the 2 way DOVER 100% silicone Foley catheter from 8 Fr. to 28 Fr. (3, 5 and 30ml) with luer lock adaptor.

CR0071 also provides clinical data on the safety and performance of a Catheter for radiation measurement. Catheter for radiation measurement: For intraurethral or intravesical placement of an in vitro dosimetry probe, as well as for introducing contrast media to the bladder, for instance in afterloading irradiation with Iridium 192 from gynecological and urological tumors.

• Vyas et al., (2013), Balloon dilatation for male urethral strictures “revisited”. Retrospective analysis study of 120 patients undergoing urethral balloon dilatation between January 2004-2012. The parameters analyzed included presentation of patients, ascending urethrogram (AUG) and descending urethrogram findings, pre- and postoperative

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International prostate symptoms score (IPSS), uroflowmetry (Qmax), and post-void residue (PVR). Need for self - calibration/ancillary procedures were assessed. The urethral balloon catheter set consists of (Cook Urological, Spencer, Indiana, USA) a 6F open-lumen, blunt-tip catheter and a 8-cm balloon that inflates fully to 24F at a maximum inflation pressure of 181 psi, using a pressure injector device. • Veeratterapillay & Pickard et al., (2012), “Long-term effect of urethral dilatation and Confidentialinternal urethrotomy for urethral strictures”. Systematic literature search for the period January 2010 to December 2011 showed that urethral dilatation and direct visual internal urethrotomy (DVIU) remain frequently used treatment options as confirmed by surveys of urologists in the USA and the Netherlands. • Xie et al., (2014). “Foley catheter versus urethral stent plus gastric tube for urine drainage following urethroplasty”. The clinical data of 361 cases of hypospadias treated by urethroplasty was reviewed. After operation, 91 of the cases received urine drainage with the Foley catheter (group A) and 270 with a urethral stent plus a gastric tube (group B). The incidence rates of bladder irritation, fistula, urethral stricture, and urethral diverticulum between the two groups of patients was compared.

7. Product Experience / Post Market Data – 2013 review The objective of this review is to evaluate clinical data for transurethral devices and / or clinical data for equivalent devices in combination with the market experience data for these devices.

Catheter Material: Latex CR0092 provides clinical data on the safety and performance of a transurethral latex balloon. CR0109 also provides clinical data on the safety and performance of a transurethral latex catheter, for example:

• In 1988, Allardice et al reported that there was no scientific data on which is the best method and catheter to use in acute urinary retention in males. These researchers compared the efficiency of a size 12 G latex rubber balloon catheter having a siliconised external finish (Warne surgical products) with a similar sized Simplastic catheter made of polyvinyl-chloride (PVC) from Dover, Scarle Medical. Both catheters had straight tips with opposed eyes. A total of 50 patients were studied (randomised to one of two groups to receive either a latex or simplistic catheter) and a 100% successful catheterisation rate was recorded at first attempt with both catheters, with no significant complications. The authors concluded that for the management of acute urinary retention, both catheter types were satisfactory.

• Goodwin and Chester, (1990) - A total of 84 patients with benign prostatic hyperplasia (n = 71) or prostatic carcinoma (n = 13) underwent assessment of urethral diameter and subsequent internal urethrotomy prior to TUP. Following resection, 42 patients received three-way self-retaining latex rubber catheters and 42 received similar catheters made of PVC. Catheters were removed when the urine was clear (mean time = 3 days), and no patient required re-catheterisation. Urinary flow was assessed in all patients at 6, 12 and 24 weeks after surgery, and diminution of flow with submeatal stricture formation was noted in one patient who had received a latex rubber catheter, and in one who had

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received a PVC catheter. In this study, the composition of the catheter had no bearing on subsequent stricture formation following TUP.

Catheter Material: PVC CR0109 provides clinical data on the safety and performance of PVC intermittent urinary catheters.Confidential The following is taken from CR0109: A comparison of the device characteristics for devices for which clinical data is available in the published clinical literature and the Medical Service GmbH SafetyCat® catheter Medical Service Hollister Coloplast Astra Tech GmbH Device Name SafetyCat® Advance (gel) EasiCath LoFric catheter (gel) (hydrophilic) (hydrophilic) Catheter PVC PVC PVC PVC material Catheter 20, 30, 40 18 – 40 18 - 40 15 - 40 lengths (cm) Catheter size 6 - 18 6 - 18 6 -22 6 - 20 (Ch.) Catheter tip Ergothan, Nelaton, Nelaton, Tiemann Nelaton, Tiemann Tiemann, Tiemann Nelaton Papers providing clinical data on the use of PVC intermittent urinary catheters for intermittent urinary catheterisation; Stensballe et al., (2005) 40 patients; Cindolo et al., (2004), 100 patients; Pachler and Frimodt-Moller (1999), 32 patients; Campbell et al., (2004), 59 patients; Vapnek et al., (2003), 49 patients; DeRidder et al., (2005), 57 patients; Sallami et al., (2011), 62 patients

Catheter Material: Silicone CR0120 provides safety and performance clinical data for silicone Foley catheters Cook Medical markets the Universa® 2-way Silicone Foley balloon catheter, which ranges from 6 to 26 Fr and 25 cm and 34 cm length and with round tip. The balloon volume ranges from 1.5, 3, 5 and 30 ml. The device is sterilised using ethylene oxide. Bard Medical markets the BARDEX LUBRICATH 2 way Foley balloon (3ml and 5ml) catheter (4, 8 to 30 Fr.). Bard Medical also markets a polyurethane urethral catheter from 4 to 6 Fr. Covidien markets the 2 way DOVER 100% silicone Foley catheter from 8 Fr. to 28 Fr. (3, 5 and 30ml) with luer lock adaptor.

Catheter Coating: The following text regarding indwelling catheter materials is taken from Geng et al., (2012) Hydrogel coated catheters are soft and highly biocompatible. Because they are hydrophilic, they absorb fluid to form a soft cushion around the catheter, and reduce friction and urethral irritation. PTFE-coated latex catheters or Teflon has been developed to protect the urethra against latex. The absorption of water is reduced due to the Teflon coating. It is smoother than plain latex, which helps to prevent encrustation and irritation. Do not use this catheter for patients who are sensitive for latex. A Cochrane review from 2007 did not find sufficient evidence to determine the best type of indwelling urinary catheter for long-term bladder drainage in adults. However, silicone catheters might be preferable to other catheter materials to reduce the risk of encrustation in long-term catheterised patients. Balloon size in adult catheters are 5 ml to 15 ml

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Balloon size in hematuria catheters 15 ml to 30 ml Bard Medical markets 2 Way specialty Foley catheters from 20 Ch. to 28 Ch. with a 75ml balloon.

Catheter Charriere size and Length: The following is taken from Geng et al., (2012) CatheterConfidential diameter sizes range from Ch 6 to 30. For paediatric use: Ch. size 6-10 For adults: Ch. size 10 Clear urine, no debris, no grit (encrustation) Ch. size 12-14 Clear urine, no debris, no grit, no hematuria Ch. size 16 Slightly cloudy urine, light haematuria with or without small clots, none or mild grit, none or mild debris. Ch. size 18, Moderate to heavy grit, moderate to heavy debris. Hematuria with moderate clots Ch. size 20-24, Used for heavy hematuria, need for flushing The standard male catheter length of 41-45 cm can be used for males and females, but a shorter female length of 25 cm can be more comfortable and discrete for some women. However, a female catheter can be too short if the woman is severely obese and then a male size is to prefer. The female length catheter should not be used for males as inflation of the balloon within the urethra can result in severe trauma. Paediatric catheters are normally about 30 cm long.

Catheter tips: PFM Medical markets the INWAY 3 Way irrigation catheter with couvellaire tip or whistle tip. The standard tip of the catheter is round with 2 drainage eyes and is called a nelaton catheter (Geng et al., 2012). The Tiemann catheter with the curved tip design is designed to negotiate the male prostatic curve and the coude tip catheter is similar to the Tiemann except it has one, two or three drainage eyes situated in the curved tip. Unomedical markets a 2 way silicone catheter with dufour tip. The dufour tip has an evenly shaped, open and angled tip with 2 sets of large opposite drainage eyes. Bard Medical markets a range of urinary catheters with 2 opposing eyes, 2 eyes on the same side, 2 staggered eyes, three staggered eyes, a single eye. These catheters are also available with different tip types – open whistle, round, coude.

Hyperthermia bladder catheter: Smiths Medical markets the Foley catheter temperature sensor. The device is made from all Silicone and is available in adult and paediatric sizes. The thermistor probe is a type series 400 temperature sensor. The device is available in from size Ch. 8 to Ch. 18. Covidien markets the Mon-a-therm® Foley catheter (all silicone) with temperature sensor. The device is available from size Ch. 8 to Ch. 18 with a 400 thermistor temperature sensor. Bard markets the temperature sensing Foley catheter with a built in temperature sensing thermistor to measure core body temperature in the bladder. The catheter is available from Ch. 8 to Ch. 18.

3 Way transurethral catheter: Cook Medical markets the Universa 3 way Silicone Foley catheter. The device is available from sizes Ch. 16 to Ch. 26, 34 cm in length and balloon volume 30ml. Covidien markets the 3 way Dover 100% silicone catheter available in size Ch. 16 to Ch. 24. The balloon volume is 5 ml or 30

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. ml. A search of PubMed using the search term “3 way Foley catheter” retrieved an article by Molsemi and Rajaei, (2010) which was included in the evaluation because the study provided clinical data on the use of a 3 way Foley catheter. Three way Foley catheters are used when irrigation of the bladder is anticipated to prevent or manage blood clots in the bladder. Effective bladder irrigation influences patient safety and clinical outcomes (Molsemi and Rajaei, 2010). These researchers carried out a prospective study to evaluate an irrigation device. A Three way Foley catheterConfidential (22 Ch. and 24 Ch.) were used in 458 cases in the study.

The following is taken from Geng et al., (2012) – reference in CR0071

Catheter type Description

One way catheter Has one channel for drainage, has no balloon. Is often referred to as a straight catheter Two way catheter Indwelling catheter with an inflatable balloon designed to secure the catheter in the bladder. One channel is used for urine and the other is used for filling the balloon Three way catheter These indwelling catheters have a 3rd channel to facilitate continuous bladder irrigation Catheter with integrated The catheter has a sensor near the tip to measure the temperature sensor temperature of the urine in the bladder

The following clinical safety and performance data is taken from CR0071:

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological Urinary bladder catheter Zmora et 118 patients Prospective, The study evaluated the use of a Clinical: The Foley catheter was drainage following pelvic al., (2011) randomized study Foley catheter following pelvic used for transurethral drainage surgery - is it necessary surgery in terms of its usefulness and (same intended use) and via the for that long? how long it is required. urethra (same site in the body). The study demonstrated that in this group of patients the Foley catheter Patients undergoing pelvic may be removed at postoperative day surgery. 1. Mean patient age = 55 years Technical: Foley catheter Biological: Foley catheter materials not described Is an indwelling catheter Sun et al., 86 patients Prospective, The study evaluated the use of the Clinical: The Foley catheter was Necessary for bladder (2004) randomized study Foley catheter and compared 2 used for transurethral drainage drainage after modified patient groups – those that had the (same intended use) and via the Burch colposuspension? catheter removed on day post urethra (same site in the body). operation and those who had the catheter removed 5 days post the Patients with stress incontinence operation. Technical: Foley catheter The results imply that it is not Biological: Foley catheter – necessary to leave the Foley catheter materials not described. in place until the fifth post operative day in order to prevent immediate voiding difficulties Suprapubic versus Bergman et 27 patients Randomized Comparison study – comparing Clinical: The Foley catheter was transurethral bladder al., (1987) suprapubic and transurethral used for transurethral drainage drainage after surgery for drainage. The study variables were (same intended use) and at the stress urinary incontinence fever and duration of hospitalization. same site in the body (via the

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological The study showed that suprapubic urethra). catheterization had a beneficial effect in terms of these variables Foley catheterization after vaginal surgery for stress incontinence

Technical: Foley catheter Biological: Foley catheter materials were not described. Postoperative voiding, Schiotz and Based on 917 Summary article The study evaluated one day Clinical: The Foley catheter was bacteriuria and urinary Tanbo, patients drainage after gynaecological surgery used for transurethral drainage tract infection (2006) with regard to impaired voiding, (same intended use) and site in with Foley catheterization asymtomatic bacteriruia and urinary the body (via urethra). after gynecological tract infection. surgery. Foley catheterization after The study demonstrated that one-day gyneaecological surgery bladder drainage by transurethral Technical: Foley catheter Foley catheter may be used routinely Biological: Foley catheter in common gynecological surgery materials were not described. with a low rate of voiding problems, asymptomatic bacteriuria, and urinary tract infection Ureteroneocystostomy: to Chow et al., 15 patients Prospective evaluation The study evaluated patients who Clinical: The Foley catheter was drain or not to drain (1998) underwent unilateral or bilateral used for transurethral drainage intravesical ureteroneocystostomy for (same intended use) and at the primary vesicoureteral reflux. All same site in the body (via patients were treated with a urethra). urethral Foley catheter. Patients who underwent unilateral

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological or bilateral intravesical ureteroneocystostomy for primary vesicoureteral reflux Age: 7 months to 19 years

Technical: Foley catheter Biological: Foley catheter materials were not described. Perioperative hypnosis Lobe, 10 patients Not described The study describes the use of the Clinical: The Foley catheter was reduces hospitalization in (2006) Foley catheter for bladder drainage used for transurethral drainage patients undergoing the while the epidural was in place for (same intended use) and at the Nuss procedure for pectus patients who underwent the Nuss same site in the body (via excavatum procedure. urethra).

Age 10 to 18 years Patients who underwent the Nuss procedure.

Technical: Foley catheter Biological: Foley catheter materials were not described. Predictors of catheter- Binhas et 164 patients Prospective The study determined the incidence Clinical: The Foley catheter was related bladder discomfort al., (2011) observational study and predictors of early postoperative used for transurethral drainage in the post-anaesthesia catheter related bladder discomfort (same intended use) and at the care unit (CRBD). Multivariate logistic same site in the body (via regression analysis showed the urethra). diameter of the Foley catheter superior than 18 Fr Patients undergoing surgery

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological and male gender to be independent under general anaesthesia predictors of moderate or severe necessitating urinary drainage. CRBD Mean age = 61 years Technical: 18 Fr. Foley catheter Biological: Foley catheter materials were not described. A prospective randomized Chai and 70 patients Prospective, The study assessed whether the Clinical: The Foley catheter was trial to compare immediate Pun, (2011) randomized controlled early or immediate removal of a 12 used for transurethral drainage and 24-hour trial Fr. Foley catheter after total (same intended use) and at the delayed catheter removal abdominal hysterectomy affects the same site in the body (via following total abdominal level of subjective assessment of urethra). hysterectomy. pain post operatively. Women were randomized to have the Women underwent total urinary catheter removed in the abdominal hysterectomies for operating room after the surgical various benign gynecological procedure or to have it removed on diseases postoperative day 1. The primary outcome was patients' pain Technical: 12 Fr. Foley catheter assessment and the secondary Biological: Foley catheter – outcomes were rate of re- materials not described catheterization and symptomatic urinary tract infection. There was no difference in the pain assessment between the two groups. A significantly higher number of urinary retention episodes requiring recatheterization were found in the immediate removal group compared

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological with the delayed removal group Management of recurrent Gargollo et 39 patients Retrospective study The study reports on 10 years of Clinical: Patients with urethral urethral strictures after al., (2010) experience with endoscopic incision strictures after hypospadias hypospadias repair: Is or dilation of urethral strictures after repair. there a role for repeat hypospadias repair. dilation or endoscopic Mean age at first stricture incision? 39 patients were treated with dilation treatment = 64.4 months. and 38% showed no recurrence of urethral stricture. Technical: The technical characteristics of the device were not describe Biological: The device materials were not described. Assessment of a new MacDiarmi 51 patients Cohort study The study investigated the use of a Clinical: Patients with urethral transurethral balloon d et al., balloon urethral dilator for the strictures. dilation catheter in the (2000) treatment of urethral strictures. The Mean age = 64.2 years (range 30 treatment of urethral device used was the Urethramax to 94 years). stricture disease. (Boston Scientific) which is a 6 Fr. Technical: the Urethramax open with a blunt tip and a 4, 6 or 8 device described in the study cm balloon that fully inflates to 24 Fr. diffes in terms of technical at maximum inflation pressure. The characteristics from the Teleflex urethramax is a urethral balloon Medical device, however, Uromed dilatation catheter. markets a dilator with technical characteristics similar to the The stricture was located in the Teleflex device bulbar, penile, and membranous Biological: The Uromed device urethra in 32, 17, and 2 patients, also contains a reinforced latex respectively; the strictures were balloon.

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological multiple in 4 patients. The strictures were between 1 and 5 cm, with a mean stricture length of 1.53 cm. This length did not take into account the presence of spongiofibrosis or “gray urethra” present in the adjacent but normal caliber urethra and probably represents an underestimation of the true stricture length. Complications were pain, mucosal tearing, hematuria.

The Uromed hydraulic urethral dilator is a radiopaque polyurethane device with a reinforced balloon and is available in size Ch. 14 to 28. The balloon is made from latex and the balloon lengths are the same as for the Teleflex device (15 or 20 cm in length). Brain and systemic Otawara et 31 patients Prospective study This study investigated the Clinical: Foley bladder catheter temperature in patients al., (2003) relationships between Brain used for bladder temperature with severe subarachnoid Temperature BT, systemic measurement. hemorrhage. temperature (ST), and clinical Patients with severe outcome in patients with severe subarachnoid hemorrhage subarachnoid hemorrhage. Technical: Foley catheter with thermistor probe

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological Thirty-one comatose patients with Biological: The materials not severe subarachnoid hemorrhage described. underwent ventricular drainage immediately after admission. The ventricular catheter also allowed monitoring of BT. ST was continuously measured using a bladder catheter with thermistor probe. BT at the start of the monitoring was lower than ST in four patients, and all died of brain swelling. BT was higher than ST at first but later fell below ST (“temperature reversal”) in 12 patients, who all died of acute brain swelling. BT was higher than ST throughout the monitoring in 15 patients. Five of these patients died of causes other than brain swelling such as rerupture of the cerebral aneurysm, multiple organ failure, or respiratory failure. The other 10 patients survived with various degrees of disability.

The catheter used for bladder temperature measurement in the study was a bladder catheter with

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Table 3. The Study title, Paper Author, Number of patients and relevant features of the clinical data to support the use of Urethral devices

Study title Paper Number of Study design Feature relevant Relevance to our product - Authors patients Clinical , Technical, Biological thermistor probe (FOLYCATH from Sheridan)

The GentleCath insertion kit contains components established for practising intermittent urinary catheterisation – for example: Gloves (vinyl) Reference: CR0109 Aseptic technique refers to disinfection of the meatus, the use of sterile materials, using a sterile lubricant or coated catheter and the introduction of the catheter without contamination (Burgdorfer et al., 2007), for example using catheter kits and gloves (Newman and Willson, 2011). Lubricating jelly: Reference: CR0109 Johnson and Johnson markets KY Jelly, which is a water soluble lubricant for surgical use. The formulation contains hydroxyethylcellulose and glycerine as lubricants and chlorhexidine gluconate as antiseptic. Antiseptic wipe: Adapta Medical Inc. markets the PerflC Cath which is intended for intermittent urinary catheterisation (510K103043). The kit includes a benzalkonium chloride wipe. The kits also includes a urine collection bag and gloves. Urine collection bag: Teleflex has many years clinical experience (documenting the safe use of urine bags for intermittent urinary catheterisation). Reference: CR0109 Film band Film band is intended to secure the wrapped components together in place for packaging

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Under Pad May be used as a privacy drape to wrap components post use for disposal

The GentleCath kit contents are established in clinical use for this particular intended purpose. There are no novel design features or materials associated with the device.

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The following side effects and complications are taken from CR0092: • Urinary tract infection • Urethritis • Urethral stricture • Hematuria • ConfidentialBladder perforation • Catheter obstruction • Urosepsis • Long catheter sign/incorrect catheter placement • Fever • Urethral trauma • Paraurethral abscess • Prostatitis • Epididymitis • Pyelonephritis • Asymptomatic bacteriuria • Catheter related bladder discomfort/pain • Catheter encrustation • Inappropriate catheter size • Pain caused by traction on the catheter bag • Urethral / meatal discomfort • Hemorrhagic pseudopolyps • Balloon cuffing

The Nelaton and Tiemann catheters are intended for intermittent urinary catheterisation. The safety and performance, side effects and complications of intermittent urinary catheters are documented in CR0109. The complications of intermittent catheterisation (reference CR0109) are: • Hematuria • Injury to a nearby organ • Urinary tract infection • Fever • Irritation • Bacteriuria • Infectious complications • Calculus disease • Bladder spasm and leakage • Renal damage • Incontinence • Local and ascending infection • Stone formation • Urethral stricture • Leukocyturia • Orchitis • Epididymitis • Urethral trauma • Urethral lesions

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• Genitourinary complications • False passage in the bulbar urethra • Discomfort / pain • Friction from insertion / withdrawal of catheter • Patient develops septicaemia • ConfidentialAcute uriticaria • Pyuria • Urethritis • Genital pathogens • Periurethral abscess • Meatal stenosis • Superficial recess • Urethral fistula • Bladder necrosis • Urethroprostatic infection

8. Product Experience / Post Market Data – 2010 review

The most common catheterisation technique for bladder drainage during hospital care is indwelling urethral catheterisation i.e. putting the catheter through the urethra into the bladder and leaving it there for a few days (Niel-Weise and Van Den Broek, 2005). There are many advantages and disadvantages associated with different types of catheterisation. In making the choice of which type of catheterisation to be used, one should consider the advantages set against possible disadvantages. The most common urinary catheter is the Foley indwelling urethral catheter, a closed sterile system that is comprised of a tube inserted through the urethra and held in place by an inflatable balloon to allow urinary drainage of the bladder (Jacobsen et al., 2008). Intermittent catheterisation provides a method of emptying the neurogenic bladder without leaving an indwelling catheter and lessens the frequency of long term complications such as hydronephrosis, bladder and renal calculi encountered with other methods of neurogenic bladder management (Bennett et al., 1995). Urological emergencies such as acute urinary retention are characterised by a sudden and painful inability to pass urine. Management of acute urinary retention involves immediate bladder catheterisation (Emberton and Fitzpatrick, 2008).

Device Performance

Manikandan et al., (2009) evaluated the flow characteristics of various 3-way catheters (14, 3- way catheters, including 18Fr, 20Fr, 22Fr and 24Fr Rusch(R), 18Fr, 20Fr, 22Fr and 24Fr Bardex(R), 18Fr, 20Fr, 22Fr and 24Fr Dover, and 20Fr and 22Fr Mentor (Mentor, Santa Barbara, California) catheters. Ten operators applied maximum 1-hand pressure with a 60 ml bladder wash syringe. Maximum and average flow rates were evaluated. The catheter was connected to an irrigation bottle and free flow irrigation speed was noted. The catheter was inserted into a latex balloon containing a prefilled volume of 100 ml and continuous irrigation characteristics were noted. Statistical analysis was performed using 1-way ANOVA and the Kruskal-Wallis test. The results showed that Rusch catheters had the best flow characteristics when the drainage port was used for manual irrigation with 18Fr catheters (Rusch and Dover 24.8 and 19.2 ml per second, P = 0.003, vs Bardex 17.67 ml per second, P <0.001), and with 20Fr Rusch, Bardex,

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Mentor and Dover catheters (27.7, 21.42, 27.1 and 24 ml per second, respectively, P = 0.034). In the other categories of catheters tested there was no significant difference among 22Fr Rusch, Bardex, Dover and Mentor catheters (29.4, 28.9, 25 and 28.27 ml per second, P = 0.32), and among 24Fr Rusch, Bardex and Dover catheters (32.2, 29.79 and 29.9 ml per second, respectively, P = 0.27). Upon using the irrigation channel for manual irrigation all catheters had similar flow characteristics (no statistically significant difference). When connected to the irrigationConfidential tube with free flow, although the 18Fr, 20Fr and 22Fr Rusch, and 24Fr Dover catheters had slightly better flow than the others, this was not statistically significant. There was no marked difference in flow rate as catheter size increased above 20Fr. When the artificial bladder was used, the Rusch catheters had the maximum drainage in the 18Fr and 20Fr sizes, whereas the Mentor and Dover catheters had the maximum drainage in the 22Fr and 24Fr sizes, respectively (no statistically significant difference). The study showed that the 18Fr and 20Fr Rusch 3-way catheters have better flow than other catheters when the drainage port is used for washout. In the 22Fr and 24Fr categories all different catheters had equivalent irrigation and drainage properties.

In a randomized trial reported by (Klarskovet al., 1986), the Bardex Urinary Drainage System was tested against a routine system consisting of a silicone-coated 16F Latex Foley catheter and exchangeable 1500 ml collecting bags. The Bardex system consists of an all-silicone balloon catheter preconnected and sealed to the drainage tube with tape. The tube is united with a 2,000 ml collecting bag via a vented drip chamber. It has an extremely hydrophilic coating (BN-74) resembling the natural glycosaminoglycans lining the urothelium. This coating is intended to minimize urethral irritation and bacterial migration and also to cause slow release of water-soluble antiseptics applied to the surface. In the present study, isobetadine 10% was applied prior to the insertion and reapplied daily after pulling gently on the catheter. Forty female patients aged 31 to 85 years completed the study. In the Bardex group of patients, bacteriuria developed in none by the third day of catheterization and in 5% by the fourth day. In the Foley group, the bacteriuria rate was significantly higher, with 35% on the third day (P<0.01) and 45% on the fourth day (P<0.02). No difference between the two drainage systems was found concerning incontinence beside the catheter, urethral pain or burning, meatal reddishness or urethral discharge.

The superiority of silicone over latex based catheters following urethral reconstructive surgery for stricture disease has been theorized, and yet data comparing their use is lacking. Erickson et al., (2008) presented findings from a prospective, randomized trial comparing silicone to hydrogel coated latex catheters in patients following urethral reconstructive surgery. From February 2004 to August 2006 men undergoing urethral reconstructive surgeries were randomized to receive an all-silicone or a hydrogel coated latex urethral catheter for postoperative bladder drainage. Patient demographics and the various reconstructive procedures used were analyzed. Complications and stricture recurrence were evaluated in the 2 groups. A total of 85 men were randomized to receive a silicone (43) or a latex (42) catheter following reconstructive surgery. Median follow-up was 20 months (range 10 to 36). Mean patient age, urethral stricture length, complication rate and type of reconstructive procedure did not significantly differ between the 2 groups. Five patients (11%) per group required repeat instrumentation for stricture recurrence (P = 0.97). Median time to stricture recurrence was not statistically different between the 2 groups. This study showed that theoretical benefit of silicone catheters over hydrogel coated latex catheters does not appear to translate into a clinical advantage after urethral reconstructive surgery since no difference in the rate of recurrence or operative complications at intermediate term follow-up was found.

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Despite the lack of evidence, using normal saline for inflating the balloon of a Foley urethral catheter is frequently regarded as a cause for deflation failure (Hui et al., 2004). These researchers investigated the issue by comparing the rate of deflation failure of Foley catheter balloon, using either sterile water or normal saline as the filling solution. Four thousand latex Foley urethral catheters (14 Fr) were randomly assigned to one of two groups: sterile water or normal saline. Each of the catheter balloons were inflated with 10 mL of the corresponding fluid. They wereConfidential subsequently put in water baths at 37 degrees celsius for 4 weeks. At the end of 4 weeks, all the balloons were deflated by people who were blind to the assignment of fluid inflated. Failure of deflation was defined as the balloon not being able to be deflated completely. The number of deflation failures was recorded and the amount of fluid aspirated from each balloon was also noted. Of the 4000 catheters, 17 (0.43%) were found to be defective and could not be used for the study. The remaining 3983 catheters were randomly allocated into the sterile water (2011) and normal saline (1972) groups. The failure rate of deflation for the sterile water group and normal saline group were 185 (9.2%) and 157 (8.0%), respectively, which was not statistically significant (P = 0.162). There was no difference in the rate of deflation failure of latex Foley balloons by using either sterile water or normal saline as the filling solution. Lawrence and Turner (2006) undertook a study developing a range of tests to enable comparison of the resistance to kinking, flow rate properties and the retention forces of both latex-based and all- silicone catheters. The results indicated that the all-silicone device had superior resistance to kinking and better flow properties when compared to the latex-based catheters. However, greater retention forces were recorded for the all-silicone device, in both the inflated and deflated condition, indicating that much more force would be required to remove the this type of catheter.

Although bladder drainage is widely used for general surgical patients undergoing laparotomy, there is little consensus on whether suprapubic or transurethral catheterization is better report (McPhailet al., 2006), who undertook a systematic database search to find all studies of suprapubic catheterization. Randomized controlled trials were identified for inclusion. Endpoints for analysis were bacteriuria, patient satisfaction and recatheterization rates. A meta-analysis was performed using fixed-effect or random-effect models as appropriate, depending on heterogeneity. The study showed that after abdominal surgery, transurethral catheterization is associated with significant bacteriuria (relative risk (RR)=2.02, P<0.001, 95 percent confidence interval (CI) 1.34 to 3.04) and pain or discomfort (RR=2.94, P=0.004, 95 percent CI 1.41 to 6.14). Recatheterization rates using the transurethral method were not increased significantly (RR=1.97, P=0.213, 95 percent CI 0.68 to 5.74) with heterogeneity between studies. Seventy five patients, needing bladder drainage for nonurological indications and having sterile urines were studied after randomization into two groups (Piergiovanni and Tschantz 1991). In the first group, drained with an urethral catheter, urinary infection took place in 12 (= 30%) patients, while it was detected in 4 (= 11%) drained with a suprapubic catheter. In this latter group, patients felt more comfortable, had less pain; the duration of urinary drainage and hospital stay was shorter. In a prospective randomized study comprising 90 women undergoing vaginal plastic surgery, suprapubic and transurethral catheter drainage of the bladder were compared regarding urinary tract infection and asymptomatic bacteriuria (Schiotzet al., 1989). No statistically significant differences were found. The mean duration of catheterization was 4.9 days for suprapubic vs 3.3 days for transurethral catheter patients. Postoperative urinary tract infection was diagnosed in 23.7% of patients with suprapubic and in 27.5% of patients with transurethral catheters. Asymptomatic bacteriuria at catheter removal was found in 21.0% of suprapubic and in 12.5% of transurethral catheter patients. More mechanical complications were seen with suprapubic catheters than with transurethral catheters. It was concluded that the two methods involve similar risks of infectious complications but that suprapubic catheters have a higher rate of mechanical complications.

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Pollack et al., (1994) compared success rates, complications, and efficiency of suprapubic bladder aspiration with urethral catheterization in ill infants. The investigation involved a prospective, randomized clinical study. Patients were randomized to undergo timed suprapubic bladder aspiration (performed by a physician and a nurse) or urethral catheterization (performed by two nurses). If suprapubic bladder aspiration was unsuccessful, urethral catheterization was performed immediately and the bladder was drained; emptying volume was recorded. All patientsConfidential had a next-void "bag" urinalysis performed for post-procedure hematuria. Fifty patients underwent primary suprapubic bladder aspiration. The success rate (defined by obtaining at least 2 mL of urine) was 46%. Mean +/- SD time per successful suprapubic bladder aspiration was 16.73 +/- 7.73 seconds. Fifty patients underwent primary urethral catheterization. The success rate was 100%; the mean time required was 80.70 +/- 46.52 seconds. After failed suprapubic bladder aspiration, urethral catheterization was 100% successful, with a mean draining volume of 2.95 +/- 2.38 mL. No immediate problems were identified among any instrumented patients; later complications (next-void hematuria after either procedure, other visceral injury with suprapubic bladder aspiration) were not detected. The authors concluded that both suprapubic bladder aspiration and urethral catheterization afford the emergency physician low-risk access to uncontaminated urine in ill infants. Suprapubic bladder aspiration is less efficient in that it requires physician participation and failure rates are higher. These data suggest that successful suprapubic bladder aspiration is primarily dependent on the volume of urine in the bladder; thus, in the ill or febrile infant who may be dehydrated, the likelihood of success decreases.

Bergman et al., (1997) reported on fifty-one patients with clinical and urodynamic diagnoses of stress urinary incontinence who were randomly allocated to either suprapubic (N = 24) or transurethral (N = 27) bladder drainage after vaginal surgery for stress incontinence (revised Pereyra procedure). Postoperative use of suprapubic bladder drainage significantly reduced febrile morbidity (P<0.01) and length of hospitalization (P<0.05). Postoperative normal bladder functions resumed more quickly when suprapubic drainage was used (P<0.05), so that most patients did not need bladder catheterization upon discharge, as opposed to more than half of those with Foley catheters, who left the hospital with a catheter in place (P<0.05). The authors concluded that it is both beneficial and cost-effective to use suprapubic bladder drainage after a Pereyra operation for stress urinary incontinence.

Perrin et al., (1997) Bladder drainage is necessary for several days following rectal surgery. Urethral catheterization has long been known to be associated with significant morbidity. A prospective randomized trial was performed to determine if this morbidity could be decreased by suprapubic catheterization. One hundred and thirty-seven patients undergoing rectal surgery were prospectively randomized to either suprapubic or urethral catheterization. After exclusions, 108 patients were analysed. Of the 49 patients with suprapubic catheters there was 14% morbidity, and of the 59 patients with urethral catheters there was 32% morbidity. Significant bacteriuria was halved with suprapubic catheterization. Patient acceptability of suprapubic catheterization was high, and there was no increased morbidity in any of the areas studied. This study suggests that suprapubic catheterization has advantages over urethral catheterization with decreased bacteriuria, and greater patient acceptability. However, the significance of decreased bacteriuria is not clear.

The duration of bladder drainage to avoid urinary retention post gynaecological surgery may vary considerably Shiotz and Tanbo, (2006). In a study by these investigators the use of 1-day drainage by transurethral Foley catheter was investigated with regard to impaired voiding, asymptomatic bacteriuria, and urinary tract infection. Furthermore, the use of methenamine hippurate was studied with regard to postoperative asymptomatic bacteriuria and urinary tract

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. infection. The study was carried out by analysing published literature and is based on six published papers totaling 917 patients. In three case series, 1-day catheterization was used in women undergoing gynaecological laparotomy, colposuspension, or vaginal plastic surgery. To compare 1- and 3-day Foley catheterization, two open, randomized trials were performed on women undergoing vaginal plastic surgery or colposuspension. The last study was a double- blind trial between methenamine hippurate and placebo as prophylaxis against urinary tract infectionConfidential and asymptomatic bacteriuria using 1-day catheterization. Postoperative voiding problems and urinary tract infection occurred infrequently with 1-day catheterization, and no more frequently than with catheterization for three days. Methenamine hippurate decreased the incidence of urinary tract infection and asymptomatic bacteriuria by 80 and 40%, respectively. One-day bladder drainage by transurethral Foley catheter may be used routinely in common gynaecological surgery with a low rate of voiding problems, asymptomatic bacteriuria, and urinary tract infection. Methenamine hippurate prophylaxis effectively reduces postoperative urinary tract infection.

Sun et al., (2004) investigated if catheterization is a mandatory procedure for adequate bladder drainage following an anti-incontinence operation until the recovery of normal voiding function occurs. A total of 86 patients with genuine stress incontinence who underwent a modified Burch coplosuspension were randomized into two groups based on the day of operation. The study group consisted of 42 patients who had the transurethral Foley catheter removed postoperatively the next morning (Group A). The control group was composed of 43 patients who had the transurethral indwelling catheter left in place until the fifth postoperative day (Group B). The percentages of immediate voiding difficulties in Groups A and B were 7.1% and 0%, respectively (P>0.05). The postoperative urinary tract infection rates of Groups A and B were 16.6% and 23.3%, respectively (P>0.05). The success rates of patients were not compromised after modified operative procedures (78.6% with dry results and 19.0% with improved symptoms in Group A vs. 74.4% with dry results and 20.9% with improved symptoms in Group B, P >0.05). The results imply that it is not necessary that an indwelling catheter, for bladder drainage, be left in place until the fifth postoperative day to prevent immediate voiding difficulties.

Dobbs et al., (1997) carried out a study to compare the infection rate and post-operative morbidity between in-dwelling urinary catheterization and 'in-out' catheterization at the time of routine total abdominal hysterectomy. The study comprised 100 patients who were blindly randomized to have either an indwelling Foley catheter or an 'in-out' catheterization at the time of surgery. Follow-up data on the retention of urine, urinary symptoms and infection were obtained. Of the 95 patients with complete data, 36% of those undergoing in-out catheterization had urinary retention after operation, requiring bladder emptying, compared with 4% of those receiving an indwelling catheter (P<0.001). In addition, 29% of the catheterized group had urinary tract bacteriuria compared with 13% of the uncatheterized group (P < 0.025). This randomized controlled trial showed that in-out urinary catheterization at the time of routine abdominal hysterectomy was associated with a significantly higher incidence of post-operative urinary retention compared with in-dwelling catheterization, and may have implications for long-term bladder function.

Intrauterine adhesion remains a common complication post dilatation and curettage (D&C) in reproductive females. Internal cervical orifice adhesion (ICA) is also observed incidentally after D&C (Lin et al., 2007), who introduced a novel adjunctive management for ICA with cross-type nelaton catheter. In this study, 20 patients suffering from amenorrhea and ICA after D&C were included. All individuals underwent flexible hysteroscopy to confirm their simple ICA statuses. All women accepted the insertion of simple cross-type nelaton catheter. Two weeks post

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. insertion, the catheter was removed and a second-look hysteroscopy was performed. Three months post catheter removal, the menstruation statuses and the efficiency of nelaton catheter in preventing ICA were evaluated. Nineteen patients had 3-month follow-up. Seventeen individuals (89.4%) had normal menstruation flow as well as the impact internal orifice of cervical canal. Only two patients (10.5%) had hypomenorrhea and fibrotic narrowing of the internal orifice of the cervix, which required resectoscopy to remove the internal cervical adhesions. All patientsConfidential appeared the competence of endurance for these procedures. The study showed that the novel cross-type nelaton catheter is a simple, well tolerated, and highly effective method for the management of ICA after D&C.

Intermittent catheterization is a commonly prescribed procedure for people with incomplete bladder emptying not managed by other methods Getliffe et al., (2007). The most frequent complication of intermittent catheterization is urinary tract infection (UTI). It is unclear what strategies, including sterile vs clean catheters or coated vs uncoated PVC catheters, affect the incidence of UTIs. A systematic review by Getliffe et al., (2007) summarizes current evidence on the relationship between sterile single-use catheters or clean reused catheters and the incidence of UTIs. The Cochrane Incontinence Group trials register, Medline, EMBASE, CINAHL, and ERIC were searched, plus the reference lists of relevant articles and conference proceedings. Randomized controlled trials comparing at least two different products or methods for intermittent catheterization were included. Of the 13 trials that met the inclusion criteria on intermittent catheterization protocols, there was considerable variation in length of follow-up, definitions of UTI, and numbers of subjects. Attrition was a problem for several studies, and all were underpowered. Several studies were more than 10 years old, and outcome measures were imprecise, making it difficult to draw conclusions on the benefit of one catheterization method over another. The findings suggested that there are no definitive studies illustrating that incidence of UTIs are affected by sterile single-use or coated catheters compared to clean reused catheters.

Dunn et al., (2003) carried out a study assessing whether the immediate removal of an indwelling catheter after the operation affects the rate of recatheterization, febrile morbidity, symptomatic urinary tract infections, or subjective pain assessments. This study was a prospective randomized controlled trial comprised of 250 women who underwent hysterectomy and who did not require bladder suspension or strict fluid treatment. The in-dwelling catheter was removed either immediately after the operation or on the first day after the operation. The association between clinical variables and the length of catheterization were assessed by chi- squared analysis. Patients were assigned randomly into 2 groups, with no significant differences in the outcomes, only in the perception of pain. Clinical events included fever (>/=38.5 degrees C) that occurred in 6 patients in the in-dwelling catheter group compared with 5 patients in the early removal group (P=0.01), symptomatic urinary tract infections in 3 patients in both groups (P=0.99), and recatheterization in 3 patients in the in-dwelling catheter group compared with 5 patients in the early removal group (P=0.17). Subjectively, patients in the early removal group reported significantly less pain than did the in-dwelling group (P<.001). The early removal of indwelling catheters after operation was not associated with an increased rate of febrile events, urinary tract infections, or need for recatheterization. In addition, subjective pain assessment was significantly less in the early removal group. The findings suggest early removal of an indwelling catheter immediately after operation is not associated with adverse events.

Roberts and Naik (2006) assessed the potential benefits of intermittent self-catheterization (ISC) over standard care with suprapubic catheterization (SPC) in the postoperative bladder care of women with early-stage cervical cancer following radical hysterectomy. A prospective

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. randomized controlled trial of 40 women was carried out. The urinary infection rate (catheter specimen of urine) was significantly higher in the ISC group at day 3 and day 5 (42% and 63%) compared to the SPC group (6% and 18%), P=0.05 and P=0.004, respectively. Forty-seven percent of patients randomized to SPC documented having problems arising from the SPC site, of which 23% were shown to have a positive wound swab. Despite a greater urinary tract infection rate, the technique of ISC was seen by women to be more acceptable, allowing fewer disturbancesConfidential at night, greater freedom to live a normal life and less anxiety/embarrassment compared to SPC.

Moore et al., (2007) carried out a review of the literature to compare sterile versus clean catheterisation technique, coated (pre-lubricated) versus uncoated (separate lubricant) catheters, single (sterile) or multiple use (clean) catheters, self-catheterisation versus catheterisation by others, and any other strategies designed to reduce UTIs in respect of incidence of symptomatic UTI, haematuria, other infections and user preference, in adults and children using intermittent catheterisation for incomplete bladder emptying. A search of the Cochrane Incontinence Group Specialised Trials Register (searched 19 June 2006), MEDLINE (January 1966 to June 2007), EMBASE (January 1988 to June 2007), CINAHL (January 1982 to June 2007), ERIC (January 1984 to June 2007) was undertaken. The selection criteria were randomised controlled trials comparing at least two different catheterisation techniques, strategies or catheter types. For dichotomous variables, relative risks and 95% confidence intervals (CI) were derived for each outcome where possible. For continuous variables, mean differences and 95% CI were calculated for each outcome. Because of trial heterogeneity, data were not combined to give an overall estimate of treatment effect. Fourteen studies met the inclusion criteria; all were small (less than 60 participants). There was considerable variation in length of follow-up and definitions of UTI. Participant drop-out was a problem for several studies. Several studies were more than ten years old and outcome measures varied between studies. Where there were data, confidence intervals around estimates were wide and hence clinically important differences in UTI and other outcomes could neither be identified nor ruled out reliably. The authors concluded that intermittent catheterisation is a critical aspect of healthcare for individuals with incomplete emptying who are otherwise unable to void adequately to protect bladder and renal health and there is a lack of evidence to state that incidence of UTI is affected by use of sterile or clean technique, coated or uncoated catheters, single (sterile) or multiple use (clean) catheters, self-catheterisation or catheterisation by others, or by any other strategy.

A retrospective review from 1995-2006 was performed by D’Cruz et al., (2009) reviewing children who sustained catheter-related injury. Six patients were reviewed over an 11-year period. All six were boys. Age ranged from <1 month to 16 years. All but one occurred in hospital. All injuries were confirmed by urethrogram. Bulbar and prostatic urethra was involved in an equal number of children studied. Three patients required suprapubic catheters. Follow-up imaging revealed healing without stricture in all patients. The authors suggested that balloon-related urethral trauma can be avoided by educating health-care professionals on proper placement and confirmation of position of catheter.

DeGroot-Kosolcharoen et al., (1988) evaluated the incidence of bacteriuria, significant urinary tract infection in a population of hospitalized adult males. A commercially available device comprised of a Foley catheter attached with a heat-shrunk plastic seal to the tubing of a closed drainage bag (preconnected system) was compared with a standard system that had the Foley catheter attached to the closed drainage bag after it had been inserted. Using a randomized prospective design, the performance of the preconnected system in 97 patients was compared with that of the standard system in 105 patients. Catheters were left in place a mean of 6.4 and

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

7.6 days in the respective groups. Bacteriuria occurred after catheter insertion in 11.3% of patients receiving the preconnected system and 13.3% of patients receiving the standard system (not statistically significant). When bacteriuria developed, it occurred within seven days of catheter insertion in 50% of instances, irrespective of drainage system employed, suggesting that manipulations related to catheter insertion were important in initiating bacteriuria.

Witjes Confidentialet al., (2009) designed a study to compare a polyvinyl chloride catheter with a new polyvinyl chloride-free catheter with the same hydrophilic coating, and determined whether patient perception of ease and comfort of clean intermittent catheterization was independent of the catheter material. This investigation was designed as a randomized, double-blind, parallel group, multicenter study. Eligible patients were experienced users of clean intermittent catheterization with a polyvinyl chloride catheter for a minimum of 1 month before randomization. They were randomized to continue to use the polyvinyl chloride catheter or switch to a polyvinyl chloride-free catheter for 4 weeks. Both catheters had a similar appearance. Patient perception of ease and comfort of clean intermittent catheterization was scored with questionnaires, and adverse events were documented. A total of 195 patients were recruited from 6 countries and 13 centres for the intent to treat analysis, and 179 were used for the per protocol analysis. Before randomization 94% to 98% of the patients rated the polyvinyl chloride catheter as easy or manageable to handle during different phases of clean intermittent catheterization and overall 92% of patients were satisfied. Of the eligible patients satisfaction was reported by 89% randomized to continue using the polyvinyl chloride catheter and by 78% randomized to switch to the polyvinyl chloride-free catheter (not significant). The rate of adverse events was low and comparable between the 2 groups. The study confirms that clean intermittent catheterization is easy and safe and conversion from a polyvinyl chloride to a polyvinyl chloride-free core catheter material does not alter patient perception of catheterization.

Cardenas and Hoffman (2009) investigated hydrophilic catheters versus noncoated catheters for reducing the incidence of urinary tract infections in a randomized controlled trial and tested the hypotheses that hydrophilic catheters reduce the incidence of symptomatic urinary tract infections (UTIs) in persons with spinal cord injury on self-intermittent catheterization (IC). Fifty six individuals on IC with recurrent UTIs met eligibility criteria. Of the 56 subjects enrolled, 45 completed the study (22 in the treatment group, 23 in the control group). There were no significant differences in demographics, including sex, between the treatment group and the controls except for more tetraplegic subjects in the control group (P0<.05). Seventy-one percent of the treatment group and 52% of the control group were men. The total number of symptomatic UTIs treated with antibiotics was significantly smaller in the treatment group than in the control group (P0<.05). Seventy percent of the control group had at least 1 antibiotic treatment episode compared with only 50% of those with the hydrophilic catheter (P=0.18). There was no significant difference in the incidence of bacteriuria or symptomatic UTIs among the 2 groups. Level of injury and years with injury were unrelated to symptomatic UTIs, but being female increased the risk of UTIs (P<0.01). Although there was no difference in the number of symptomatic UTIs in the 2 groups, hydrophilic catheter usage was associated with reduced numbers of treated UTIs as compared with standard nonhydrophilic catheters in persons with spinal cord injury who used self-IC; however, the study is limited by a small sample size.

Janelli et al., (2007) compared the risk of significant bacteruria between clean intermittent self- catheterization (CISC) and suprapubic catheterization (SPC) after urogynaecologic surgery. Patients were randomized to CISC or SPC. A urinalysis and patient satisfaction questionnaire were conducted on postoperative days 2 and 7. Urine culture was performed for positive urinalysis. Significant bacteruria was defined as > 100,000 cfu/mL (colony forming units per

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. millilitre). To detect a decrease in bacteruria risk from 25% to 10%, 113 subjects per group were needed with 80% power and alpha of 0.05. Of 248 randomized patients, 210 were included in the final analysis. The overall risk of bacteruria was 27% with no difference between SPC and CISC (31% vs 23%, P = 0.23). Patients reported more frustration (P = 0.01) and more difficulty (P = 0.003) using CISC. There was no difference in risk of significant bacteruria between CISC and SPC.Confidential Side Effects

Up to 25% of hospitalised patients undergo urinary catheterisation and about 5% develop bacteriuria each day of catheterisation (Saint and Lipsky, 1999). The most notable complication associated with indwelling urinary catheters is the development of nonsocomial urinary tract infections, known as catheter associated UTI’s (Jacobsen et al., 2008). Anderson (1979) studied the urethral and bladder cellular proliferation after exposure to latex, silicone-coated latex, and 100% silicone catheters. Fifty-one male patients were studied and no differences in acute cellular reaction could be detected among the three different catheter materials.

Al-Habadan et al., (2003) carried out a randomised study to investigate catheter-related nosocomial urinary tract infection in postoperative orthopedic and trauma patients. The patients were studied prospectively using nitrofuroxone-impregnated urinary catheters (study group) and regular silicone-coated Foley catheters. Fifty adults in each group were randomly assigned. In Group A, antibiotic-impregnated catheters were used, and in the other, non-antibiotic- impregnated urinary catheters were used (Group B). The variables studied were age, sex, type of surgery, duration of surgery, number of catheter days, days of intravenous line, and hospital days. In patients, urinary tract infection (UTI) was diagnosed by culture and the organism was isolated. The average age in the study group was 43.90 years (range, 14-95 years) compared with the control group (mean age, 42.22 years; range, 14-102 years). Catheter days in the nitrofuroxone-impregnated catheters was 7.9 days (range, 2-37 days) versus 7.2 days (range, 2- 30 days). The intravenous line in the group was 9.16 days (range, 2-35 days) versus 8.8 days (2- 22 days). There were six infections (P = 0.028) in the control group compared with the study group. The length of operation was similar in each group. The study indicated that nitrofuroxone- impregnated catheters have the potential to reduce nosocomial catheter-related UTIs in postoperative orthopedic and trauma patients.

Benoist et al., (1999) carried out a controlled trial comparing 1 versus 5 days of transurethral catheterization after rectal resection, with special reference to urinary tract infection and bladder retention. One hundred and twenty-six patients undergoing rectal resection were included in a prospective randomized study designed to compare the results for patients undergoing 1 day of transurethral catheterization after rectal resection (1-day group) with those for patients undergoing 5 day catheterization (5-day group). Patients were randomly assigned to the 1-day and 5-day groups (n = 64 and 62, respectively). Clinical findings and surgical procedures were comparable in both groups. Acute urinary retention occurred in 16 patients (25%) in the 1-day group versus 6 (10%) in the 5-day group (P < .05). Urinary tract infection was observed in 13 of 64 patients (20%) in the 1-day group versus 26 of 62 (42%) in the 5-day group (P<0.01). Multivariate analysis revealed that after 1 day of catheterization carcinoma of the low rectum and lymph node metastasis were significant risk factors for acute urinary retention (P < .05 for both factors). After selection of patients without low rectum carcinoma, the acute urinary retention rate was comparable in both groups (14% in the 1-day group versus 7% in the 5-day group), but the urinary tract infection rate was significantly lower in the 1-day group versus the 5-day group (14% vs 40, P < .01). The controlled study showed that after rectal resection 1 day of urinary drainage

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. can be recommended for most patients. Five-day drainage should be reserved for patients with low rectal carcinoma.

In a single case report Murakami et al., (2004) report how a 7-year-old boy with microtia was scheduled for otoplasty under general anesthesia. A Foley catheter was indwelt very gently following tracheal intubation but his foreskin showed remarkable edema about 15 minutes later. All vitalConfidential signs were normal. His lungs were ventilated easily and no rash or edema was found except for penis. Operation was completed uneventfully as planned. He recovered from anesthesia smoothly but foreskin edema still remained. Allergic reaction was suspected and scratch test was performed to determine the allergen on the next day. Positive reaction to Foley catheter extracts and high serum latex-specific IgE antibody level proved that latex containing Foley catheter had caused foreskin edema. The authors highlight that all anaesthesiologists should pay attention to latex allergy and interview all patients in detail in pre-anaesthetic evaluation.

Treatments

Niel Weise and Van Den Broek (2005) carried out a literature search to determine if certain antibiotic policies are better than others in terms of prevention of urinary tract infections, complications, quality of life and cost-effectiveness in short-term catheterised adults. A search of the Cochrane Incontinence Group Specialised Register was conducted. All randomised and quasi-randomised trials comparing antibiotic policies for short-term (up to and including 14 days) catheterisation in adults were selected for analysis. Six parallel-group randomised controlled trials met the inclusion criteria. In one trial comparing antibiotic prophylaxis with giving antibiotics when clinically indicated amongst female surgical patients who had a urethral catheter for more than 24 hours, symptomatic urinary tract infection was less common in the prophylaxis group (RR 0.20, 95% CI 0.06 to 0.66). Five trials compared antibiotic prophylaxis with giving antibiotics when microbiologically indicated, bacteriuria, pyuria and gram-negative isolates in patients' urine were less common in the prophylaxis group amongst surgical patients with bladder drainage for at least 24 hours postoperatively. Bacteriuria rates were also about five-fold lower in the prophylaxis group in trials involving urological surgery patients and non-surgical patients. No trial compared giving antibiotics when microbiologically indicated with giving antibiotics when clinically indicated. There was weak evidence that antibiotic prophylaxis compared to giving antibiotics when clinically indicated reduced the rate of symptomatic urinary tract infection in female patients with abdominal surgery and a urethral catheter for 24 hours. The limited evidence indicated that receiving antibiotics during the first three postoperative days or from postoperative day two until catheter removal reduced the rate of bacteriuria and other signs of infection such as pyuria and gram-negative isolates in patients urine in surgical patients with bladder drainage for at least 24 hours postoperatively. There was also limited evidence that prophylactic antibiotics reduced bacteriuria in non-surgical patients.

Stricker and Grant (1988) prospectively randomised one hundred patients into two groups to receive either a single dose of 1 g ampicillin and 80 mg gentamicin pre-operatively or no antibiotic prophylaxis. The incidence of breakage in the continuity of the closed drainage system was documented. All patients with urinary tract infection (UTI), catheterisation, clinical prostatic carcinoma, neurogenic bladder and bladder tumours were excluded. UTIs, bacteraemia and fever were noted. There were 7 late exclusions. The incidence of UTI in the control and antibiotic groups was 16 and 17% respectively. No blood cultures were positive. There were no significant differences in the incidence of fever between the two groups. A break in the closed drainage system occurred in 13 patients. Fifteen of the 93 developed UTI. A break in the closed

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. drainage system occurred in 7 of the 15 patients (40%) with UTI. Of the 78 patients without UTI, 8 had a break (10%). This difference was highly significant. Stricker and Grant (1988) recommended that less emphasis be placed on prophylactic antibiotics and more on avoiding breakage of the closed system in the prevention of UTI after transurethral resection of the prostate in the low risk situation

Leone Confidentialet al., (2004) carried out a review and analysis of the literature concerning the diagnosis, prevention, and management of catheter-associated urinary tract infection (CAUTI) occurring in patients hospitalized in the intensive care unit (ICU). Analysis was performed from personal and "Pubmed" data, crossing the following keywords: "urinary tract infection", "catheter', and "intensive care unit". Few clinical trials including ICU patients were found despite the abundance of expert opinions. There is no consensus on the use of urinary reagent tests for diagnosis. Neither complex closed drainage systems nor silver-coated urinary catheters have demonstrated efficacy in comparative randomized clinical trials. The administration of prophylactic antimicrobial therapy, although effective in reducing the incidence of urinary bacteria, cannot be recommended in ICU patients. The management of CAUTI in ICU patients has not been evaluated in clinical trials. The level of evidence provided in this field is weak, and underlines the need for randomized studies to improve management of patients.

Gribble and Puterman (1993) designed an experiment to determine the efficacy of trimethoprim- sulfamethoxazole (TMP-SMX) for prophylaxis of urinary tract infection in persons with recent spinal cord injury, during the first 4 months of intermittent catheterization. One hundred and twenty-nine adults (112 men, 17 women) with recent acute spinal cord injury participated in a randomized, double-blind, placebo-controlled trial, and were studied for up to 16 weeks. Low- dose TMP-SMX (TMP 40 mg, SMX 200 mg) or placebo was given once daily. Clinical observations, urine cultures, and cultures of rectal and urethral swabs were made weekly. Subjects who developed breakthrough bacteriuria received conventional antimicrobial therapy and prophylaxis was continued. Sixty-six TMP-SMX recipients (57 men, 9 women) and 60 placebo recipients (52 men, 8 women) were evaluable for efficacy. Among male subjects, bacteriuria was present during 50% or more of study weeks in 30% of TMP-SMX recipients and in 56% of placebo recipients (P = 0.003). The interval to the onset of bacteriuria was prolonged in TMP-SMX recipients (P< 0.0001). TMP-SMX recipients without bacteriuria in any given week had a lower probability of having bacteriuria the subsequent week (0.26) than did placebo recipients (0.49) (P < 0.0001). At least 1 episode of definite symptomatic bacteriuria (and fever and at least 1 classical manifestation of urinary infection) occurred in 4 of 57 TMP-SMX-treated men and in 18 of 52 placebo-treated men (P < 0.0003). Similar trends were observed in women, but differences did not reach statistical significance, perhaps because the number of females was small. Adverse events suspected to be due to medications were frequent in this population of patients with recent severe injuries and led to discontinuation of the study in 10% of the TMP- SMX group and 8% of the placebo group. Adverse events included neutropenia (TMP-SMX: two; placebo: three), pseudomembranous colitis (TMP-SMX: one), severe skin rash (TMP-SMX: two; placebo: one), and drug fever (TMP-SMX: one). The proportion of all episodes of bacteriuria that were due to TMP-SMX-resistant organisms was unexpectedly high in the placebo group (51%), and increased progressively according to year of enrollment in the study. By Year 3, all subjects in the placebo group had at least one episode of TMP-SMX-resistant bacteriuria. Gram-negative enteric bacilli resistant to TMP-SMX were recovered from rectal swabs (TMP-SMX 49%, placebo 42%) and urethral swabs (TMP-SMX 33%, placebo 26%) in similar proportions of subjects in the two study groups. Prophylaxis with TMP-SMX significantly reduces bacteriuria and symptomatic urinary tract infection in persons with recent acute spinal cord injury during bladder retraining using intermittent catheterization. However, adverse reactions attributable to TMP-SMX are

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. common in this population. Colonization and breakthrough bacteriuria with TMP-SMX-resistant organisms are frequent and may seriously limit the usefulness of this strategy, particularly in an institutional setting.

Takeuchiet al., (1993) evaluated the clinical efficacy and safety of a Foley catheter coated with silver-protein (ProAg catheter) in the prevention of catheter-associated bacteriuria. ProAg catheterConfidential significantly reduced the incidence of extraluminal catheter-associated bacteriuria compared with usual latex Foley catheter although it did not inhibit intraluminal bacteriuria. There was no difference between ProAg catheter and latex catheter in the side effects such as urethral discharge, catheter-associated pain and allergic reaction. The ProAg catheter may be useful as an indwelling urethral catheter.

Agarwalet al., (2005) sought to discover the incidence and severity of bladder discomfort in patients who were catheterized intraoperatively and to evaluate the efficacy of tolterodine, a pure muscarinic receptor antagonist, in preventing this. Two-hundred-fifteen consecutive adult patients, ASA physical status I and II, either sex, undergoing urologic surgery requiring bladder catheterization were enrolled. Group C (control, n = 165) received placebo and group T (tolterodine, n = 50) received tolterodine 2 mg. Drugs were administered orally 1 h before surgery. After induction of anaesthesia, patients were catheterized with a 16F Foley catheter and the balloon was inflated with 10 mL of normal saline. In the postanaesthesia care unit, bladder discomfort was assessed on arrival (0), 1, 2 and 6 h. Severity of bladder discomfort was graded as mild, moderate, and severe. Bladder discomfort observed in group C was 55% (91 of 165). Tolterodine reduced both the incidence 36% (18 of 50) and severity of bladder discomfort (P0< 0.05). Bladder discomfort secondary to an indwelling urinary catheter is distressing to patients. In the present study, it was observed that tolterodine (2 mg), a competitive muscarinic receptor antagonist administered 1 h before surgery, reduced both the incidence and severity of bladder discomfort secondary to bladder catheterization.

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Adverse events for “urinary catheter” cited on the Bfarm website over the period 2013 to 2016

Patient risk as Device Company Description of problem Action Date described We understand well 2 Way, JIANGSU In a hospital in Germany, it was Recall and March 2016 that if a catheter is 14 Fr. SUYUN found that our all silicone catheter is destroy invisible under X- Silicon MEDICAL invisible under X-ray testing. The way may cause the e MATERIALS tubing catheter can be detected inconvenience issue catheer CO., LTD under the X-ray equipment, because during the operation the materials added a certain process proportion of barium sulfate, causing part of the products is not development or not development sufficiently maybe because of the uneven ratio of barium sulfate. But even a catheter’s X-ray line is invisible, due to this defect in patients risk is almost zero. Professional medical person can operate successfully without X-ray machine assistant. We understand well that if a catheter is invisible under X-way may cause the inconvenience issue during the operation process. Use of nonsterile Magic3 BARD Package seal void. Recall July 2015 Magic3TM Female TM

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Adverse events for “urinary catheter” cited on the Bfarm website over the period 2013 to 2016

Patient risk as Device Company Description of problem Action Date described Intermittent Hydrop Catheters could hilic- introduce coated microorganisms to Female the urinary tract Intermi during a ttent catheterisation Cathete procedure which rs may lead to a varying degree of risk including localised and/or systemic infectious complications ranging from urinary tract infection to urosepsis. In the event this occurred, the patient may require medical intervention.

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

Complaint data has been evaluated routinely since product launch as part of ongoing product post market surveillance. Details of the complaints for the Transurethral devices are shown in the Tables below. Confidential Table 4. Complaint data for the hyperthermia bladder 2 way 100% silicone catheter devices over the period 2008 - 2011 Experience observed Year 2008 2009 2010 2011 Total

Volume of sales 370 350 0 0 720 Frequency of experience (%) 0 0 0 0 0

Table 5. Complaint data for the 2 and 3 way simplastic catheter devices over the period 2008 – 2011 Experience observed Year 2008 2009 2010 2011 Total Buggy Balloon 1 1 0 1 3 Blocked Lumen 1 0 4 1 6 Burst Balloon- Simplastic 2 0 8 14 24 Cannot passed thru cannula 1 0 0 0 1 Reterioration 1 0 0 0 1 Incorrect Dimension 4 0 0 0 4 Leak- Simplastic 5 0 2 44 51 Leak/Torn ET 2 0 0 0 2 Lumen Contriction 1 0 0 0 1 Non Deflation 4 1 5 11 21 Non Inflation 3 0 0 0 3 Burst ET Cuff 1 0 0 0 1 Irrigation Problem 2 0 0 0 2 Leak Funnel 0 1 1 0 2 Poor Bounding 0 1 0 0 1 Kink 0 2 0 0 2 Incorrect Dimension 0 2 0 0 2 Poor Coating 0 4 0 0 4 Leak-Water Sschet 0 13 0 0 13 Difficult to Remove 0 1 0 0 1 Bent/ Distored/Deformed 0 1 1 0 2 Wrong Product 0 1 0 0 1

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

Design Change/divided 0 1 0 0 1 Balloon lifting 0 0 0 15 15 Defective valve 0 0 0 13 13 Volume of Sales 430220 10155020 354060 587670 11526970 FrequencyConfidential of experience (%) 0.007 0.0003 0.006 0.02 0.008

Table 6. Complaint data for the latex Foley catheter devices over the period 2008 - 2011

Experience observed Year 2008 2009 2010 2011 Total Block Lumen 10 12 2 1 25 Burst Balloon 6 8 6 6 26 Catheter Broke 5 8 1 2 16 Fitting 1 1 0 0 2 Foreign Matter 13 17 2 2 34 Incorect Dimension 3 5 9 1 18 Leak 13 13 0 0 26 Non Deflation 27 40 28 24 119 Non Drainage 1 2 0 15 18 Non Inflation 12 29 28 19 88 Inner Packaging Trapped 1 1 0 0 2 Side Arm Catheter Inflated 2 5 0 0 7 Discolouration 3 6 1 0 10 Mislabelling 1 1 0 0 2 Balloon asymmetry 11 11 9 5 36 Collapse Lumen 1 1 0 1 3 Poor Sealing 1 1 0 0 2 Stuck Stylet 1 3 0 5 9 Discolouration 3 0 0 0 3 Partial Non Deflation 0 1 0 0 1 Deterioration 0 2 0 1 3 Blister 0 2 0 0 2 Blockage 0 1 0 0 1 Bent/Distorted/Deformed 0 3 1 1 5 Colour Variation 0 1 0 0 1 Crack 0 2 0 0 2 Faulty Valve 0 2 0 0 2 Leak Balloon 0 10 20 14 44 Leak Funnel / urine bag detachment 0 4 0 1 5

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Leak Drainage 0 3 5 4 12 Loose Connector 0 3 0 0 3 Loose Valve Fitting 0 2 5 7 14 Mix Size 0 1 0 0 1 No LabelConfidential 0 1 0 0 1 Poor Sealing 0 1 1 5 7 Protuded Stylet 0 1 0 0 1 Wrong Product / label 0 1 2 2 5 Defective Product 0 2 4 10 16 Defective Valve 0 1 0 0 1 Misuse 0 3 0 0 3 Swelling of urethra after insertion 0 0 1 0 1 Volume of Sales 15415080 16154966 11831725 1409758 5749936 9 0 Frequency of experience (%) 0.0007 0.001 0.0010 0.0008 0.0009

Table 7. Complaint data for the Nelaton Type Catheter devices over the period 2008 - 2011

Experience observed Year 2008 2009 2010 2011 Total Wrong Quantity 1 0 0 0 1 No Inflation 1 0 0 0 1 Misc 0 1 0 0 1 Drainage problem 0 0 2 0 2 Wrong size 0 0 0 1 1 Volume of Sales 1768741 2031693 2681779 1417295 7899508

Frequency of experience (%) 0.000113 0.000049 0.00007 0.00007 0.00007

Table 8. Complaint data for the pre-connected drainage system with latex Foley catheter devices over the period 2008 - 2011

Experience observed Year 2008 2009 2010 2011 Total Faulty Valve 3 0 0 0 3 Leak 2 0 0 0 2 Incorrect dimension 0 0 3 3 6 Volume of Sales 28280 36900 45020 48480 158680

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Frequency of experience (%) 0.017 0 0.007 0.006 0.008

TableConfidential 9. Complaint data for the Catheterisation Set devices over the period 2008 - 2011

Experience observed Year 2008 2009 2010 2011 Total Volume of Sales 0 0 0 0 0 Frequency of experience (%) 0 0 0 0 0

Table 10. Complaint data for the PVC intermittent catheter devices (and water sachet) over the period 2008 – 2011

Experience observed Year 2008 2009 2010 2011 Total Open Seal/ Poor Sealing 6 0 15 0 21 Poor Bonding/ Detachment 13 1 0 0 14 Poor Coating 2 4 1 3 10

Foreign Matter 8 0 0 0 8 Seal Cannot Open 1 0 18 0 19 Leak 1 10 1 0 12 Rough Surface 1 0 12 0 13 Incorrect Dimension 1 2 0 0 3 Leak Funnel 0 1 0 0 1 Kink 0 2 0 0 2 Leak-Water Sachet 0 13 18 31 62 Difficult to Remove 0 1 0 1 2 Bent/ Distorted/Deformed 0 1 0 0 1 Wrong Product / label 0 1 1 0 2 Design Change/divided 0 1 0 0 1 Difficult to insert 0 0 4 0 0 Sticky catheter 0 0 3 15 18

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Wrong quantity in package 0 0 3 0 3

Volume of Sales 10073320 12196670 4837750 5320010 32427750 Frequency of experience (%) 0.00032 0.0003 0.0016 0.0009 0.0008

Confidential

Table 11. Complaint data for the Ureteral connector devices over the period 2008 - 2011

Experience observed Year 2008 2009 2010 2011 Total Volume of Sales 600 1320 0 0 1920 Frequency of experience (%) 0 0 0 0 0

2-Way & 3-Way Latex Foley Catheter (Class IIa) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015 Balloon asymmetry 7 7 0 0 Deformed balloon 0 1 1 2 (blister, defective, torn, etc.) Defective catheter 0 0 13 2 Funnel blew up, deflation on wrong 0 1 0 0 side of catheter Balloon leak 15 12 22 14 Catheter becomes rigid 0 0 1 0 Blockage (drainage lumen) 7 13 21 17 Non-drainage/ slow drainage 5 0 1 0 Burst balloon 2 3 9 5 Wrong quantity in package 0 0 2 0 Catheter broke - shaft 5 0 1 3 Discoloration of catheter/ purple 9 1 6 2 syndrome (due to medication) Funnel/ valve detachment from 1 7 3 1 catheter shaft Funnel-urine bag detachment 7 0 1 0 Tip came off/ disloged/ broke 2 0 0 0 Incorrect dimension (e.g.inflation lumen/ funnel/ drainage lumen/tip) 0 0 20 0

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Leak catheter (Y-junction, shaft, 8 0 8 3 funnel) Deformed or missing components/ 1 0 24 0 accessories Non deflation/ difficult to deflate/ 54 62 104 83 partial deflation Non inflation/Confidential slow inflation (due to leak/defective valve etc.) 42 1 104 32 Damage Packaging 3 0 0 0 Foreign matter 2 0 0 0 Missing product/ empty pouch 1 0 0 1 Difficult to insert catheter 0 0 0 2 Wrong size 0 0 0 2 Defective/ broken syringe (i.e hole) 0 0 0 11 Wrong product 0 0 0 1 Difficult to remove stylet 0 0 0 2 Odor/ chemical smell from catheter 0 0 0 1 Difficult to remove catheter 0 0 0 2 Volume of Sales 15,769,782 16,651,100 13,549,131 12,335,125 Complaint frequency (%) 0.001 0.0006 0.003 0.002

2-Way & 3-Way Simplastic Catheter (Class IIa) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015 Burst balloon (i.e.due to degradation 5 3 6 3 of latex balloon) Burst balloon (post operative use) 0 1 0 0 Leak balloon 4 13 7 1 Non deflation/ partial deflation 7 5 12 5 Non inflation 0 7 0 1 Catheter kink 1 0 0 0 Foreign matter 0 1 1 0 Blockage (irrigation lumen) - 3Way 0 0 1 3 Non drainage, blockage (drainage 6 1 0 0 lumen) Leak catheter 15 0 0 0 (Y-junction, shaft, funnel) Pleated balloon 0 2 2 1

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

Balloon detachment/ dislodge 2 4 3 1 (routine drainage) Balloon detachment/ dislodge (post 0 1 0 1 operative use) Volume of Sales 445,610 445,610 486,380 455670 ComplaintConfidential frequency (%) 0.009 0.009 0.007 0.004

PVC Intermittent Catheter & Saline Water Sachet (Class Is) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015 Poor coating 7 17 1 10 Rough surfaces on catheter 0 0 42 0 Leak/Empty water sachet 2 0 5 142 Hard seal water sachet/ difficult to 3 0 2 0 burst Leak/ defective Luer connector 1 2 2 4 *applicable for Flocath Plus only Inappropriate/incorrect label 0 5 0 0 Incorrect dimension 0 0 7 0 Product or component trapped/ 0 17 112 0 sealed in package Wrong product 1 0 0 0 Broken/dislodge/torn/cracked tip 1 0 0 45 Rough tip 0 1 0 10 Difficult to open pouch 2 14 1 0 Allergy 30 0 1 0 Missing Component (i.e. water 0 0 0 1 sachet) Catheter stick to packaging 0 0 0 141 Catheter broke 0 0 0 1 Missing Product 0 0 0 4 Improper flow of saline solution 0 0 0 10 Folded blue sleeve 0 0 0 8 Foreign matter 0 0 0 1 Volume of Sales 5,353,625 6,136,970 5,071,210 5,964,330 Complaint frequency % 0.001 0.001 0.003 0.006

Hyperthermia Bladder 2 Way 100% Silicone Catheter (Class IIa) Complaint Mode (Defect) Complaint Qty

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2012 2013 2014 2015 Leak balloon/cuff 1 0 0 0 Volume of Sales 565 700 800 900 Complaint frequency % 0.18 0 0 0 Confidential

Ureteral Connector (Class IIa) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015

N/A 0 0 0 0 Volume of Sales 840 1200 1080 600 Complaint frequency % 0 0 0 0

Catheter Set (Class IIa) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015

N/A 0 0 0 0 Volume of Sales 4240 3980 6720 3,660 Complaint frequency % 0 0 0 0

Preconnected Drainage System with Latex Foley Catheter (Class IIa) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015

Leak urine bag 0 2 0 1 Volume of Sales 31,060 21,840 37,520 40 300 Complaint frequency % 0 0.009 0 0.002

Nelaton Type Catheter (Class Is) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015 Difficult to use 0 0 4 0 Wrong labelling 0 5 0 0 Deformed tip 0 0 0 4

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Volume of Sales 569,065 578,240 594,850 1,834,516 Complaint frequency % 0 0.0009 0.0007 0.0002

Confidential2 Way 10ml All Silicone Catheter for Radiological Display (Class IIa) Complaint Qty Complaint Mode (Defect) 2011 2012 2013 2014 2015 N/A 0 0 0 0 0 Volume of Sales 316 344 300 300 225 Complaint frequency % 0 0 0 0 0

GentleCath Kit & Catheter Insertion Kit (Class II per FDA classification) Complaint Qty Complaint Mode (Defect) 2012 2013 2014 2015 N/A 0 0 0 0 Volume of Sales 4240 3980 6720 989,340 Complaint frequency % 0 0 0 0

9. Risk Analysis / Review The risk analysis identified both risks associated with the design and use of the device. A multi- functional team considered the use of the device and identified the characteristics related to the safety of the medical device. The identification of hazards and the sequence of event(s) leading to hazardous situation(s) was conducted from both the product and user perspective (including foreseeable misuse). Both normal and fault conditions for the device were considered. Mitigation measures (controls) have been put in place to minimize the risk to the patient and user. The risk profile of the device is acceptable considering the benefits to the patient.

10. PubMed Database search strategy results The database search strategy is outlined in CP0101. The PubMed search terms, number of articles retrieved based on those search terms and the number of articles included based on the inclusion and exclusion criteria defined in the protocol CP0101 are shown in Table below.

Table 13. The PubMed database search strategy results - search terms, number of hits and the number of articles included in the evaluation based on the search criteria Search Term Number of Hits Number of 2015 Number 2015 Number articles included of Hits of articles included Transurethral 23 0 36 0 catheterization AND side effects

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Transurethral 65 0 58 0 catheterization AND complications

A searchConfidential of the PubMed literature did not retrieve new safety and performance issues associated with these devices. A number of clinical reports are cross referenced in this report because these reports already contain safety and performance clinical data for equivalent devices. The search terms and strategy are also documented in these reports (CR0109, CR0092, CR0120, and CR0071). 2014 Update: The literature review did not retrieve any new side effects and complications associated with these devices. This is not surprising as these are established devices based on well known technologies.

11. Product Literature and Instructions For Use Clinical data from the peer reviewed literature has been reviewed for safety and performance data, side effects and complications associated with urethral devices. The review has shown that there are side effects and complications associated with these devices.

However, as per EN1041:2008, product information and labelling shall be part of risk management procedures. EN ISO14971:2012 provides guidance on overall residual risk evaluation and review of warnings provided in the IFU (Annex D); “a warning on its own could provide adequate risk reduction, however too many warnings can reduce the effect of individual warnings”. The devices considered in this report are based on well known, technologies with substantial clinical data available for equivalent devices.

Based on the review, the information contained in the instructions for use is deemed appropriate for these devices.

12. Device Equivalency The review of the literature has demonstrated that the devices grouped as transurethral and equivalent devices are in widespread clinical use. These devices are based on established technologies and there are no novel features associated with these devices.

a. Clinical Parameters The review has retrieved clinical data for equivalent devices which are used for the same clinical condition, at the same site in the body and have similar relevant critical performance according to the expected clinical effect. The catheters considered in the report are either indwelling or for intermittent use. The Foley catheter has been used for bladder drainage for many decades and is an established technology. Intermittent catheters without a balloon are also an established technology and clinical data describing their safety and performance is documented in CR0109.

b. Technical Parameters The review has retrieved clinical data for equivalent devices which are used under similar conditions of use, have similar specifications, similar deployment methods and principles of operation. The catheters considered in the report are supplied with or without a balloon. The

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone. catheter charriere size and length of the Teleflex urethral devices are within the range of those devices described in the literature.

c. Biological Parameters The devices are made from well known and established materials for their particular intended use. ThereConfidential are no novel materials incorporated into the design of these devices. 13. Market experience data The devices considered in this report are based on established technologies with a considerable history of safe clinical use. The review considers documented market sales and complaint data over the 2008 to 2014 period. The value of clinical experience data is that it provides real world experience obtained in larger, heterogeneous and more complex populations, with a broader (and potentially less experienced) range of end users than is usually the case with clinical investigations).

14. Author Objectivity The authors of the clinical evaluation report possess the appropriate qualifications and experience2 to conduct a clinical evaluation for these devices. The authors possess knowledge of the device technology and its application, research methodology (clinical investigation design, biostatistics, bioinformatics); and diagnosis and management of the conditions intended to be treated or diagnosed by the device. Objectivity was ensured by using pre-defined search terms/keywords in the protocol. The keywords used to search the PubMed database do not differentiate between favourable and unfavourable data.

15. Post Market Clinical Follow Up No Post Market Clinical Follow Up is required for these devices because the medium/long term clinical performance and safety is already known from previous use of equivalent devices. In addition, Teleflex Medical carry out the following actions (1). All received complaints and adverse events data are systematically reviewed, and all product related adverse events such as those described in Annex II 3.1 of the MDD are notified to the relevant Competent Authority. This includes all sources of information known by the manufacturer, including published literature. (2). Monitoring of postmarket performance also takes into account relevant data publicly available with similar devices.

16. Summary and Conclusion

The clinical evaluation of these devices was performed as defined in Annex X of the Medical Devices Directive 93/42/EEC as amended by 2007/47/EC. The report includes an evaluation of the data from information published in the literature relating to equivalent devices. The report is based on the literature route as specified in the Medical Device Directive Annex X and MEDDEV 2.7.1 Rev 3 and SG5N2R8.

2 Note regarding authors: Details of the qualifications and experience of the above are held on file.

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

The potential for duplication of data across multiple publications was considered and based on a review of the retrieved data (study populations, dates authors), no reporting on duplicated data exists.

The review of the literature for this device has included a comprehensive search of the literature. Data were retrieved based on the search terms specified in the protocol (see CP0101). Each individualConfidential dataset included in this evaluation has been assessed in terms of relevance, applicability, quality and clinical significance. During the data retrieval process studies based on randomised controlled trials were searched and reviewed for relevance with preference due to the nature of the design of these trials and the weighting and validity applicable to such data.

A review of the literature has shown that these devices currently represent the state-of-the-art in current medical practice.

It is believed that all relevant references, both favourable and unfavourable, have been captured for these devices. This is due to the nature of the search terms, specified in the protocol (CP0101).

The review of the literature has shown a consistency of results for the performance and safety of these devices across the retrieved studies. Indeed, in combination with the complaint data this information allows us to conclude that these devices are suitable for their intended use.

A review of the clinical data from the literature for Transurethral devices demonstrates: • Transurethral devices fulfil the requirements for their specified characteristics and performance, under the intended conditions and for their intended purpose of use. • These devices do not pose any undue safety concerns either to the recipient or end-user. • The risks associated with the use of these devices are acceptable when weighed against the benefits to the patient.

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17. References Annex X Medical Device Directive 93/42/EEC as amended by 2007/47/EC

MEDDEV 2.7.1 Rev 4 (2016) Clinical evaluation: Guide for manufacturers and notified bodies Confidential GHTF SG5/N2R8 (2007) GHTF Clinical Evaluation

ENISO14971:2012 – Application of Risk Management to medical devices

ENISO10993-1:2009 – Biological Evaluation of medical devices – Part 1: Evaluation and testing within a risk management process

WI0061 Clinical Evaluation Work Instructions

NBOGs Best Practice Guide CL2010 -1

MEDDEV 2.12/2 rev2 (2012) Guidelines on Medical Devices - Post Market Clinical Follow-up Studies. A guide for manufacturers and notified bodies

CR0071 Clinical Evaluation Report Urethral (Willy Rusch)

CR0109 Clinical Evaluation Report SafetyCat Chlorhexidine Ampoule Family of Products (Medical Service GmbH) –intermittent catheters

CR0107 Clinical Evaluation Report Phthalates

CR0092 Clinical Evaluation Report Transurethral (Athlone)

CP0101 Clinical Evaluation protocol Transurethral (Malaysia)

CR0120 Clinical Evaluation Report Transurethral IIb (Malaysia)

Agarwal A, Raza M, Singhal V, Dhiraaj S, Kapoor R, Srivastava A, Gupta D, Singh PK, Pandey CK, Singh U. The efficacy of tolterodine for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study. Anesth Analg. 2005 Oct;101(4):1065-7

Al-Habdan I Fau - Sadat-Ali, M., J. R. Sadat-Ali M Fau - Corea, et al. "Assessment of nosocomial urinary tract infections in orthopaedic patients: a prospective and comparative study using two different catheters." (0020-8868 (Print)).

Anderson, R. U. Response of bladder and urethral mucosa to catheterization. JAMA. 1979 Aug 3;242(5):451-3

Benoist S., Panis, Y., C. and Denet, et al. Optimal duration of urinary drainage after rectal resection: a randomized controlled trial. Surgery. 1999 Feb;125(2):135-41

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

Braasch M, Antolak C, Hendlin K, Botnaru A, Herrera S, Lavers A, Canales B, Monga M. Irrigation and drainage properties of three-way urethral catheters. Urology. 2006 Jan;67(1):40-4.

Cardenas DD, Hoffman JM. Hydrophilic catheters versus noncoated catheters for reducing the incidence of urinary tract infections: a randomized controlled trial. Arch Phys Med Rehabil. 2009 Oct;90(10):1668-71. Confidential Carol J. Bennett, Mary Nancy Young, Rodney H. Adkins and Frances Diaz. Comparison of Bladder Management Complication Outcomes in Female Spinal Cord Injury Patients The Journal of Urology Volume 153, Issue 5, May 1995, Pages 1458-1460

Chene G Fau - Boulard, G., J. P. Boulard G Fau - Gachie, et al. "[A controlled trial of a new material for coating urinary catheters]." (0002-1148 (Print)).

D'Cruz R, Soundappan SS, Cass DT, Smith G. Catheter balloon-related urethral trauma in children. J Paediatr Child Health. 2009 Oct;45(10):564-6. Epub 2009 Sep 14.

DeGroot-Kosolcharoen J, Guse R, Jones JM. Evaluation of a urinary catheter with a preconnected closed drainage bag. Infect Control Hosp Epidemiol. 1988 Feb;9(2):72-6.

Dobbs et al. Effectiveness of Five Different Approaches in Management of Urinary Tract Infection: Randomised Controlled Trial 1997 BMJ. 2010;340: Drekonja DM, Kuskowski MA, Wilt TJ, Johnson JR. Antimicrobial urinary catheters: a systematic review. Expert Rev Med Devices. 2008 Jul;5(4):495-506.

Dunn TS, Shlay J, Forshner D Are in-dwelling catheters necessary for 24 hours after hysterectomy? . Am J Obstet Gynecol. 2003 Aug;189(2):435-7.

Emberton, M. and Fitzpatrick, J. The Reten-World survey of the management of acute urinary retention: preliminary results BJU International Volume 101 Issue s3, Pages 27 - 32

Erickson Ba., Navai, N., M. and Patil, et al. A prospective, randomized trial evaluating the use of hydrogel coated latex versus all silicone urethral catheters after urethral reconstructive surgery. J Urol. 2008 Jan;179(1):203-6.

Getliffe K Fau - Fader, M., C. Fader M Fau - Allen, et al. "Current evidence on intermittent catheterization: sterile single-use catheters or clean reused catheters and the incidence of UTI." (1071-5754 (Print)).

Gribble MJ, Puterman ML. Prophylaxis of urinary tract infection in persons with recent spinal cord injury: a prospective, randomized, double-blind, placebo-controlled study of trimethoprim- sulfamethoxazole. Am J Med. 1993 Aug;95(2):141-52.

Hinz J, Rosmus M, Popov A, Moerer O, Frerichs I, Quintel M. The Reten-World survey of the management of acute urinary retention: preliminary results. BJU Int. 2008 Mar;101 Suppl 3:27-32.

Hui J., Ng C.F., Chan L.W. et al. Can normal saline be used to fill the balloon of a Foley catheter? Otolaryngol. 31, 344. 3 (2004)

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Confidential - may not be reproduced, distributed or disclosed without prior consent from Teleflex EMEA Athlone.

Jacobsen, S. M D. J. Stickler, H. L. T. Mobley, and M. E. Shirtliff, Complicated Catheter- Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis. CLINICAL MICROB IOLOGY REVIEWS, Jan. 2008, p. 26–59 Vol. 21, No. 1

Jannelli ML, Wu JM, Plunkett LW, Williams KS, Visco AG. A randomized controlled trial of clean intermittent self-catheterization versus suprapubic catheterization after urogynecologic surgery. Am J ObstetConfidential Gynecol. 2007 Jul;197(1):72.e1 -4.

Joseph R Fau - Ramesh, P., R. Ramesh P Fau - Sivakumar, et al. "Tensile set behavior of Foley catheter balloons." (0021-9304 (Print)).

Klarskov P and Bischoff, N., A. and Bremmelgaard, et al. Catheter-associated bacteriuria. A controlled trial with the Bardex Urinary Drainage System. Acta Obstet Gynecol Scand. 1986;65(4):295-9.

Kozer E, Rosenbloom E, Goldman D, Lavy G, Rosenfeld N, Goldman M. Pain in infants who are younger than 2 months during suprapubic aspiration and transurethral bladder catheterization: a randomized, controlled study. Pediatrics. 2006 Jul;118(1):51-6.

Lawrence El Fau - Turner, I. G. and I. G. Turner "Kink, flow and retention properties of urinary catheters part 1: conventional foley catheters." (0957-4530 (Print)).

Leone M., Garnier, F. and Avidan, et al. Catheter-associated urinary tract infections in intensive care units. Microbes and Infection Volume 6, Issue 11 September 2004, Pages 1026-1032

McPhail Mj., Abu-Hilal, M., C. D. and Johnson, et al. A meta-analysis comparing suprapubic and transurethral catheterization for bladder drainage after abdominal surgery. Br J Surg. 2006 Sep;93(9):1038-44

Manikandan R, Selvaratnam V, Philip J, Hanlon A, Machin DG, Williamson M. Evaluation of flow characteristics of 3-way catheters. J Urol. 2009 Apr;181(4):1922-5. Epub 2009 Feb 23.

Moore KN, Fader M, Getliffe K. Long-term bladder management by intermittent catheterisation in adults and children. Cochrane Database Syst Rev. 2007 Oct 17;(4).

Murakami T, Kayo R, Kajita I, Cho S, Saito H. A case of latex allergy induced by indwelt Foley catheter. Masui. 2004 Jun;53(6):675-8.

Niel-Weise Bs and van den Broek, P. J. Antibiotic policies for short-term catheter bladder drainage in adults. Cochrane Database Syst Rev. 2005 Jul 20;(3):

Perrin Lc., Penfold, C., A. and McLeish, et al. A prospective randomized controlled trial comparing suprapubic with urethral catheterization in rectal surgery. Aust N Z J Surg. 1997 Aug;67(8):554-6

Piergiovanni M and Tschantz, P. Urinary catheterization: transurethral or suprapubic approach? Helv Chir Acta. 1991 Jul;58(1-2):201-5

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Pollack Cv Jr., Pollack, E. S. and Andrew, et al. Suprapubic bladder aspiration versus urethral catheterization in ill infants: success, efficiency and complication rates. Ann Emerg Med. 1994 Feb;23(2):225-30.

Roberts K, Naik R. Catheterization options following radical surgery for cervical cancer. Br J Nurs. 2006Confidential Oct 26-Nov 8;15(19):1038-44. Schiotz Ha., Malme, P. A., and Tanbo, et al. Urinary tract infections and asymptomatic bacteriuria after vaginal plastic surgery. A comparison of suprapubic and transurethral catheters. Acta Obstet Gynecol Scand. 1989;68(5):453-5

Schiotz Ha. and T. G. Tanbo. Postoperative voiding, bacteriuria and urinary tract infection with Foley catheterization after gynecological surgery. Acta Obstet Gynecol Scand. 2006;85(4):476- 81

Stricker Pd. and A. B. Grant. Relative value of antibiotics and catheter care in the prevention of urinary tract infection after transurethral prostatic resection. Br J Urol. 1988 Jun;61(6):494-7

Sun Mj., Chang, S.-Y. and Lin, et al. Is an indwelling catheter necessary for bladder drainage after modified Burch colposuspension? Int Urogynecol J Pelvic Floor Dysfunct. 2004 May- Jun;15(3):203-7

Takeuchi H, Hida S, Yoshida O, Ueda T. Clinical study on efficacy of a Foley catheter coated with silver-protein in prevention of urinary tract infections. Hinyokika Kiyo. 1993 Mar;39(3):293-8.

Witjes JA, Del Popolo G, Marberger M, Jonsson O, Kaps HP, Chapple CR. A multicenter, double-blind, randomized, parallel group study comparing polyvinyl chloride and polyvinyl chloride-free catheter materials. J Urol. 2009 Dec;182(6):2794-8.

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18. Appendices; Appendix 1. Authors CVs

John McDonald Ph.D. Education:

Ph.D. MolecularConfidential Biology (University College Dublin) – includes training on bioinformatics Expert in experimental design and development, data assessment and analysis Developed molecular diagnostic assay based on real time reverse transcription technology for the detection of viral RNA in plants Developed molecular diagnostic assay based on polymerase chain reaction technology for the detection of pest DNA in natural predators in cereals

Postgraduate in Statistics (University College Dublin)

Postgraduate in Information Technology/Computer programming (Dublin City University) 1H1

Experience

Manager of Regulatory Germany and Regulatory Science International, Teleflex Medical

Research and Development Engineer at Allergan Medical. Design and Development of Class III implant devices Expert in Process optimization - DOE

Research and Development Scientist at Trinity Biotech plc. Design and development of hemostasis invitro diagnostic reagants Technical support of hemostatsis products Process optimization -DOE

Dr John O Dwyer MB, BCh, BAO, M.Med.Sc, MBA

Irish Medical Council Registration number: 17663

Education & Primary Degree

• Medical Degree (MB, BCh, BAO) - National University of Ireland, Galway 1987 -1993 Postgraduate Qualifications:

• Master degree in Medicine (M. Med. Sc.) - National University of Ireland, Galway

• Master degree in Business Administration (MBA) - University of Limerick

• Affiliated member of faculty of Pharmaceutical Medicine, Royal College of Physicians

Professional Appointments

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• Medical Intern/House Officer in Medicine in University Hospital Galway (UHG) - July 1993 -1994 • Senior House Officer & Registrar in Anaesthesia in UHG & Irish Hospitals - Jan 1995 - Confidential1998 • Senior Clinical Reviewer in National Standards Authority Ireland (NSAI) - Jan 1999 - 2004 • Medical Director & European Manager in Medical Devices Dept.(NSAI) - Jan 2005 - Mar 2014 • Medical Director EMEA in Teleflex Medical Europe - April 2014 - presently

Postgraduate Achievements & Training:

• Masters degree in Business Administration (MBA) - majoring in Strategic and Risk Management, with thesis on ‘the Strategic Management of Clinical Investigations’ - University of Limerick. • Masters degree in Medicine (M.Med.Sc.) - majoring in Medical Informatics with thesis on ‘Evidence-based Medicine in regulating drug eluting stents’ – National University of Ireland. • European Manager & Medical Director in NSAI for the Medical Devices Directive (MDD) and associated medical directives – working with Competent Authorities, EU Commission & Clients. • Cochrane Library Review & Clinical Review Research training – Health Research Board • Medical Device Risk Management Training ISO 14971 • Medical Devices Directive Revisions training • Continuous Medical Education (CME) training with Royal College of Physicians - updating clinical review expertise and clinical decision making skills • Member of European ‘Clinical Investigation and Evaluation Working Group’ for Medical Devices • Previous member of Notified Bodies Working group (NB- MED) in Europe. • Member of Clinical Trials Taskforce Committee within the IMDA Clinical/Regulatory Experts. • Guest lecturer/ presenter at global Clinical and Regulatory medical device meetings discussing regulatory and clinical review requirements.

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• Member of the Association of Pharmaceutical Physicians of Ireland (APPI). Previous Member of National University of Ireland, Galway Medical Alumni Board.

Confidential

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19. Appendix 2. Device Codes

5706 5143 851143 (664130) 4426 187005 850002 DP2101 S189205 Confidential5708 4456 5143021 851142 (664176) (663630) 187030 850003 DP3101 S189230 5709 4462 5143025 850251 (664575) (661610) 189205 850004 P2101 611502 4212 4466 5104 851621 (650610) (661630) 189230 850006 P3101 4216 4516 5104R 851622 (650630) (664330) 180105 850010 185503 5700 3510 851631 4226 (664230) 181305 850241 186005 4266 5704 5105 851632 (651630) (663230) 181330 850243 186030 4316 611400 851641 (654330) 5501 180605 189003 4190 4516 5707 851221 851642 (664330) (662530) 180630 189305 7051 851241 851643 5508 652410 183430 189330 9813 5710 850218 611500 5730 (662675) 183230 180705 186505 5711 850219 611402 5732 (662630) 183405 180730 181100 5712 851121 611602 5736 (662575) 183530 180630 179373 851122 220800 5738 664275 183630 183430 173705 4262 851131 220850 5739 (651610) 183830 3171 76200 4412 851132 220900 (660610) 187500 183930 3181 503870 5702 4416 851141 (664530) (660630) 180003 183960 3183 3365

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20. Approvals

Function Approval Date

OriginatorConfidential Regulatory John McDonald Ph.D. Per COF1658 Affairs Manager Director of RA and QE, Gary Fahey Per COF1658 International, QA Clinical/Medical Dr. John O’Dwyer Per COF1658

Quality Assurance Pusparajah Selvadurai Per COF1658

Regulatory Affairs Chuah Siew See Per COF1658

Revision History

COF# Date Revision Reason Training for Change Requirements

0076 17 May 2010 AA Original Issue N/A 0315 28-March- AB Clarification of device N/A 2011 Hyperthermia bladder 2 way 100% silicone catheter and PVC Catheter in section 3. 0785 11 Jan 2013 AC Update with recent post market N/A surveillance data 1116 08- May-2015 AD Update to include GentleCathTM N/A kit 503870. Also to delete codes no longer sold and shelf life expired 1206 14-Sept-2015 AE Update to include 2 Way All N/A Silicone Catheter for Radiological Display. 1658 04 Jan 2017 AF Update with recent post market N/A surveillance data

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