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bionector Handbook

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Bionector Handbook Technical Support Data for Bionector

Handbook Contents Section 1:

Microbial Contamination Studies

Section 2:

Blood and Fluid Reflux Testing

Section 3:

Blood Administration and Blood Sampling

Section 4:

Design and Functionality

Section 5:

Validation of Bionector as a 360 Access Device

Section 6:

Material Choice

Section 7:

MRI Study

Section 8:

Directions for use

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SECTION 1 - Microbial Contamination Studies Bionector Clinical Performance Study - N° 1 and N° 4 1. Membrane/Septum Disinfection Can Bionector be disinfected using standard hospital cleaning policy ?

4. Microbial Ingress Test Does Bionector resist the ingress of bacteria into the patient’s vasculature ?

bionector Clinical Performance Study 1 ®

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Can Bionector be effectively disinfected? Background

Conclusion

As more and more needleless devices are brought to market, some manufacturers/suppliers have made claims regarding hypothetical superior ‘cleanability’ of their device due to the design and construction of the device’s membrane. Some customers tell us that they have been shown a test using ultraviolet light to demonstrate that their device glows less than Bionector after it is cleaned. Another manufacturer/supplier will tell you that even if you don’t clean their device it will transmit fewer bacteria to the patient’s vascular access device than Bionector.

If Bionector is cleaned using an appropriate disinfectant, no bacteria is transmitted to the patient’s vascular access device. We would urge you to ask any manufacturer who makes a claim that their needleless device is more ‘cleanable’ than Bionector to show you a comparative microbiological report that proves it.

As part of our ongoing programme of product development, we tested the ‘cleanability’ of the Bionector membrane using the latest cleaning agent at the respected Health Protection Agencies (HPA) Porton Down Laboratory in Wiltshire UK in May 2009.

Objective To demonstrate that the Bionector membrane can be effectively disinfected.

Test summary & results Ten Bionectors were assessed to check whether they prevent microorganisms entering the patients bloodstream. Prior to the test a sterile 100mm extension line was connected to the male luer of the Bionector. A sterile 5ml syringe filled with PhosphateBuffered Saline (PBS) was luer-locked onto the female end of the Bionector, and 2ml of the saline solution was passed through the device. Each Bionector was then deliberately contaminated on the external surfaces of the female luer using a microbial culture, staphylococcus epidermidis NCIMB 12721. The inoculated Bionectors were allowed to dry at room temperature for 30 minutes. The contaminated surface was swabbed for approximately 5 seconds using sterile 2% chlorhexidine in 70% alcohol wipes (Sanicloth). After the cleaning process, a sterile 5ml syringe was filled with sterile nutrient broth, and 2ml of broth was passed through the inoculated and swabbed Bionector into a culture tube containing culture broth. The culture tube was incubated at 37°C for 72 hours and observed daily for any growth. The culture tubes showed no growth of staphylococcus epidermidis. Therefore, under these test conditions there was no evidence of penetration of microorganisms into the sterile line when the Bionector was swabbed with a sterile disinfectant.

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SECTION 1 - Microbial Ingress Testing Bionector Clinical Performance Study - N° 4

bionector® Clinical Performance Study 4

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Can we conclude that Bionector is truly a closed system? Background

Conclusion

More and more emphasis is being put on how needleless devices function and the impact that this has on the transmission of bacteria into the patient’s vascular access device and thus infection. Many manufacturers suggest that transparent needleless devices are the way forward for helping to identify when the device either needs to be replaced or when flushing has been effective (see section 3 for Bionector flushing evaluations). In terms of the device needing to be replaced, being able to see inside the device is not a very conclusive way to ensure that bacteria has not colonised the space, because bacteria is of course, microscopic.

No growth occurred after 48 hours incubation at 30ºC ± 2ºC in 500ml of sterile saline (x 5) travelling through five sterile Bionectors (male/female luer-lock connector), pre-damaged to simulate a crack in the female luer of the casing. The Bionectors had been immersed in a high concentration suspension (>108cfu/ ml) of Brevundimonas diminuta for over 24 hours to create a worst-case scenario. Under these rigorous test conditions, there is no evidence of bacteria entering the sterile line.

Objective As part of our ongoing programme of product development, we deliberately contaminated the internal mechanism of Bionector with bacteria. We then tested the device to see if any of this bacteria could be transmitted to the patient’s vascular access device.

Test summary & results In 2007 we tested Bionector at the respected Health Protection Agencies (HPA) Porton Down Laboratory in Wiltshire UK. Five Bionectors (male/female luer-lock connector), pre-damaged to simulate a crack in the female luer of the casing, were individually connected upstream via tubing to a sterile saline bag and downstream to a sterile collection vessel. The five Bionectors were then immersed in a suspension of more than 108cfu/ml Brevundimonas diminuta over a 24 hour period.The saline was run through the Bionector and tubing, and held for a 24 hour period. After this time, the remaining fluid in the five bags was emptied via the Bionector and tubing into the five downstream collection vessels over a one hour period.The saline collected in each of the downstream vessels was filtered through a 0.2μm polycarbonate filter.The filters were then placed onto agar plates and incubated at 30ºC ± 2ºC for 48 hours. The five filters showed no growth of Brevundimonas diminuta. Therefore, under these test conditions, even with a crack in the female luer, there was no evidence of penetration of microorganisms into the sterile line.

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SECTION 2 - Blood and Fluid Reflux Testing Bionector Clinical Performance Study - NÂ° 2 Is Bionector a neutral pressure/displacement needleless device, and how does it compare to other needleless devices available on the market ?

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bionector Clinical Performance ( Study 2 ÂŽ

Is Bionector a neutral pressure/displacement needleless device, and how does it compare to other needleless devices? Background

Conclusion

Catheter occlusion is a major problem in terms of the management of vascular access devices. A number of papers currently recommend the use of neutral pressure needleless devices to help combat the problem. As part of our ongoing programme of product development, we tested the effect on blood movement at the tip of a vascular access device when a syringe or administration set is connected to Bionector.

Due to the unique way in which Bionector functions, under test conditions the device displayed the least blood reflux into the tip of a VAD compared to our competitors. The results concluded that our best performing competitor demonstrated 125% more reflux and our worst performing competitor demonstrated 1,950% more reflux.

0.068

0.033

0.01

0.009

BIONECTOR

0.078

Competitor C

In 2007 we asked Nelson Laboratories in the USA to test Bionector along with a number of other needleless access devices currently available on the global market.

Competitor A

Test summary & results

Competitor E

Competitor D

To demonstrate that Bionector creates the least movement of blood at the distal tip of a vascular access device when compared to our competitors, and thus can be confirmed as a neutral pressure needleless device.

Competitor G

Objective

0.004

Test set-up: 2ml of red colouring was added to one litre of saline. The IV connector sample was attached to the 2Fr PICC tubing. A syringe was connected to the sample. Coloured saline was flushed through the IV connector and the tubing to prime the set-up.

IV line connector detachment: With the tubing primed to the distal end, the syringe was detached from the IV connector. The amount of fluid movement at the distal tip was measured with a ruler. The line was reprimed for the next sample. The IV line connector detachment phase was performed on eight different samples at five replicates per sample.

IV line connector attachment: After the tubing was primed, the syringe was connected to the IV connector. The amount of fluid movement was measured with a ruler. The line was re-primed for the next sample. The IV line connector attachment phase was performed on eight different samples at five replicates per sample.

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SECTION 3 - Blood Administration and Blood Sampling Bionector Clinical Performance Study - NÂ° 3A and 3B 3A. I s it safe to sample blood through Bionector and can we conclude that the blood is not damaged ? 3B. Is it possible to clear blood from Bionector following blood administration or blood sampling ?

bionector Clinical Performance Study 3A ÂŽ

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I s it safe to sample blood through Bionector and can we conclude that the blood is not damaged ?

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bionector Clinical Performance Study 3B ®

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Is it possible to clear blood from Bionector following blood administration or blood sampling? Background More and more emphasis is being put on the ability to prove that blood can successfully be flushed/eliminated from needleless devices. This is due to the risk of biofilm formation which can increase the risk of catheter colonisation and thus catheter related blood-stream infection. Some needleless devices have a clear housing so the fluid pathway can be visualised post-flush. Of course having a transparent housing does allow the user to determine when macroscopic blood is present. However, can they conclude at what point microscopic blood has also been eliminated?

Objective To demonstrate that Bionector can be successfully flushed and to conclude experimentally what volume of flush is required to eliminate blood from the device.

Test summary & results Inoculation of blood into valve Prior to the procedure, ensure the blood is stored at room temperature. Attach a 1ml syringe to the proximal end of a Bionector and attach a needle to the distal end. Draw the blood (volume approximately 0.7ml). Expel the blood from the Bionector and remove the needle. Flush the Bionector with three 5ml boluses of sterile 0.85% saline solution. Obtain each 5ml bolus by successively flushing 1ml aliquots; collect each of these three washes into sterile test tubes.

2. Dilute number 1 above 1:1 = 1:500 (5ml of Standard 1 + 5ml of Drabkin’s) = Standard 2. 3. Dilute Standard 2 above 1:1 = 1:1,000 (5ml of Standard 2 + 5ml of Drabkin’s) = Standard 3. Allow to stand for five minutes and then read at 540nm. Set the spectrophotometer to zero using Drabkin’s reagent. Run Standard 3, followed by Standard 2, then Standard 1; this will give a standard curve. Take some blood and allow it to reach room temperature for one hour as above, then dilute the blood as above 1:250, 1:500 and 1:1,000 with the Drabkin’s reagent. Follow the same procedure (standard runs), starting run with the Drabkin’s reagent for blank, followed by the lowest dilution concentration to the highest. After a 5ml bolus has been collected and analysed in Drabkin’s reagent, test its absorbance as above. Start the test with bolus No. 3, followed by No. 2, and finally, No. 1. The absorbance of each of the three boluses will be calculated from the standard curve to determine haemoglobin content. Most of the recovery is expected to be obtained in the first bolus.

Conclusion The test results demonstrate that blood can effectively be flushed from Bionector using normal saline. 99.57% of the blood challenged was cleared with the first 5ml flush, 99.97% was cleared with the second 5ml flush and 99.99% was cleared with the third 5ml flush.

Concentrate the red blood cells collected in the bolus by centrifugation for 10 minutes at approximately 2,500rpm. Dissolve the pellet produced in 5ml of Drabkin’s reagent to release haemoglobin.

Determination of haemoglobin Prepare haemoglobin (standard catalogue No. 3075). Prior to the process, bring the ampoule to room temperature for at least one hour. Immediately before use, hold the ampoule between the thumb and index finger and swirl the ampoule gently by inverting for 30 seconds, allowing bubbles to rise before opening.

Procedure (standard runs): 1. Dilute the standard 1:250 (0.1ml + 24.9ml) = Standard 1.

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SECTION 4 - Design and Functionality Bionector Clinical Performance Study - N° 5 Is Bionector a split septum or mechanical valve needleless connector?

bionector Clinical Performance Study 5 ®

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How does Bionector function? Background

Summary

Following the publication of the CDC guidelines(2), there has been a great deal of discussion regarding the design of needleless connectors and their functionality. Our Clinical Performance Studies regarding microbial ingress and membrane/septum disinfection conclude that Bionector can be cleaned effectively and resists the entry of bacteria to the patients’ vasculature. However, according to the CDC classification, is Bionector a split spetum or mechanical valve needleless connector?

Bionector has an internal pin which interfaces with the split in the septum of the membrane from below as the tip of a syringe or infusion set depresses the membrane during connection. Bionector is best defined as a split septum needleless connector in terms of its functionality.

Objective To define which of the above categories defines the functionality of Bionector.

Split Septum

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SECTION 5 - Validation of Bionector as a 360 access device

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Can Bionector be suitable for use up to 360 accesses ? Introduction This report summarises the validation of Bionector as a 360 access device, with reference to the tests carried out and the results found. Bionector has been initially tested to validate the acceptable number of uses, and production batches are subjected to random sample testing to ensure continued compliance. Bionector is produced in such high volumes that the test machines run almost constantly performing these production sample tests.

Method Testing equipment is used to simulate repeated access to the sample Bionector devices. Each sample Bionector is attached to the testing machine, then subjected to repeated accesses using a syringe barrel. Each sample is subjected to an initial 100 accesses before being checked for the following: •L eaks: The Bionector is connected to a pressurised system and checked for any visible leaks. Testing is carried out at 700 mbar of counterpressure. • Membrane deformation: The membrane should return to its original resting position and should show no signs of being deformed. •M embrane movement: The membrane must remain contained in the Bionector casing and should not be either partially or completely expelled from the device. •P resence of shavings: There should be no evidence of plastic or polyisoprene becoming detached from the Bionector, which could lead to the product failing to function correctly.

Bionector access simulation

The samples are then subjected to further repeated accesses and tested at fixed intervals until failure is reported, or until 360 accesses have been made with no reported failure.

Conclusion The needleless I.V. access device Bionector has been tested and proven to be suitable for use up to 360 accesses. No leaks or shavings were found, and the membrane returned to its original resting position after each use.

Validation Reports • Validation report 04227 for initial production batch testing. • Validation report 00294 testing Bionector to determine the maximum number of accesses. • Quality Control Document Ref C2083 testing membrane function after repeated accesses.

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SECTION 6 - Material Choice

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Is Bionector Octopus tubing in polyurethane compatible with all commonly infused drugs and IV solutions ? Bionector Octopus Tubing is made from Polyurethane Polyurethane is an ideal material as it is compatible with all commonly infused drugs and IV solutions. It can be confidently recommended for use where accurate and predictable delivery of drugs is required.

The following section is a collaboration of information relating to materials choice, and their interaction with drugs.

SECTION 6 - Material Choice

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THE PROBLEM DRUG INFUSIONS In recent years the development of continuous infusion of numerous drugs by syringe driver/heparin pump has become commonplace within theatres, ICU/CCU and on wards. The constant blood serum levels obtainable, increased patient comfort and the accurate control of critical and potent drugs are recognised benefits of this method of administration. The range of drugs now infused includes anticoagulants, insulins, analgesics, sedatives, inotropics, vasodilators, antibiotics and the list continues to grow.

PLASTICS AND DRUG INTERACTIONS The interaction of drugs with medical plastics is complex and there are many published papers addressing this problem. The material most frequently implicated in significant interactions is Polyvinyl Chloride (PVC). This material is commonly used by manufacturers of administration sets and IV container bags and drug infusion lines. Adsorption, Absorption and Permeation are all types of interaction where the delivered dosage, (clinical effect or the composition of the drug) is compromised by the plastic with which it comes into contact. Conversely an interaction known as migration can occur in which the additives used in the manufacture of the finished product migrate into the drug itself possibly producing undesirable effects. All forms of interaction pose problems and may compromise patient care in certain patient groups. For example, cardiac patients may be compromised because of the well documented reports of interaction losses experienced when Nitroglycerin or Isosorbide is in contact with PVC extension tubes. The losses experienced are unpredictable and occur over a time span when most control is required, i.e. during the first few hours of infusion when the drug dosage is being adjusted to produce the desired clinical effect. Rapid falls in drug potency occur, for example with Nitroglycerin a low point of only 26% remaining potency at 90 minutes from start of infusion has been reported. This massive loss of 74% occurred whilst infusing Nitroglycerin through a six foot PVC drug infusion line from a glass bottle. Following this low point the potency of the drug starts to rise, which will again require frequent adjustment of infusion rate to compensate for the increasing dosage being received by the patient.

THE SOLUTION POLYURETHANE FOR SAFE, RELIABLE AND ACCURATE INFUSIONS Polyurethane is the ideal drug infusion line material as it is compatible with all commonly infused drugs and IV solutions. It can be confidently recommended for use where accurate and predictable delivery of drugs is required. Small bore drug infusion lines have low priming volumes minimising expensive drug wastage. A 1mm internal diameter drug infusion line also exposes the lowest possible surface area to drug plastic interactions. Drug infusion lines manufactured in medical grade, high density Polyurethane are recommended in reports as the material with the least or only very minor interactions compared to PVC.(1,2,3,4,5,6,7,8,9)

COMPATIBILITY OF POLYURETHANE Polyurethane is compatible with Nitroglycerin and Isosorbide and will deliver a constant dosage eliminating the possibility of over or under delivery of critical drugs, which reduces the constant manipulation of delivery rate needed to compensate for variable losses experienced.

SECTION 6 - Material Choice

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SECTION 6 - Material Choice

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Why is material choice important? Drug-plastic interaction is increasingly being recognised as a major problem(10,19) when intravenous solutions are being infused via administration sets which are incompatible with many commonly used drugs. If an infusion line is manufactured from PVC (which is not compatible with several commonly used drugs)(13,19-21) one of three events may occur: Adsorption, Absorption or Permeation. Adsorption onto PVC

Adsorption Adsorption is where the drug binds to the inner surface of a plastic drug infusion line, but it does not penetrate any further than this.(22) The initial effect is the reduction of drug concentration delivered to the patient. The inner surface then becomes saturated and the concentration of the drug in the solution increases rapidly.(23) Substances which are most likely to adsorb are Diazepam(13,20,24,25) ,insulin(13,26,27) ,nitroglycerin(13,21,24,28), Propofol(13,29) and interferons.(30)

Absorption into PVC

Absorption Absorption is where the drug actually migrates into the wall of the plastic infusion line.(17) The drug concentration in the infusate is initially low and slowly begins to recover as the plastic becomes saturated. Substances which are most likely to be absorbed are Chlorpromazine(31) and Nimodipine(32).

Permeation through PVC

Permeation Permeation is where the drug migrates through the plastic wall and out onto the outer surface of the infusion line where it evaporates.(33) Losses from permeation can be substantial and they continue throughout the duration of infusion as the plastic never becomes saturated. Substances which are most affected by permeation are nitrates(1) and Chlormethiazole(33).

SECTION 6 - Material Choice

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SECTION 6 - Material Choice

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References 1. HANSS P, et al. Intravenous nitroglycerin perfusion techniques - clinical implications.

Pharmacy, September 1982; 16, (9): 689-692.

Intensive Care Med, 1982, 8, 93-95. 19. Kowaluk EA, Roberts MS, Polack AE. Interactions between drugs and intravenous 2. KOWALUK ET, et al. Interactions between drugs and intravenous delivery systems.

delivery systems. American Journal of Hospital Pharmaceutics, 1982; 39: 460–7

Am Journal Hosp Pharm, 1982, 39, 460-467. 20. Yliruusi JK, Uotila JA, Kristoffersson ER. Effect of flow rate and type of I.V. container 3. SAUTOU V, et al. Compatibility with medical plastics and stability of continuously and simultaneously infused isosorbide clinitrate and heparine. Int Journal of

on adsorption of diazepam to I.V. administration systems. Am J Hosp 1986; 43: 2795–9.

Pharmaceutics, 1994, 107, 111-119. 21. Schaber DE, Uden DL, and McCoy HG. Nitroglycerin adsorption to a combination 4. Sautou Miranda, et al. Compatibility with medical plastics and stability with coadministered drugs of isosorbide clinitrate and heparin during continuous infusions.

polyvinyl chloride, polyethylene intravenous administration set. Drug Intelligence & Clinical Pharmacy, 1985; 19, (7): 572-575.

Journal of Pharm Clin, 1995, Sept, Vol 14, No.3. 22. Shibata N et al. Adsorption and pharmacokinetics of Cyclosporin A in relation to 5. D’ARCY PF. Drug interactions with medical plastics. Drug Intell Clin. Pharm., 1983, 17, 726-731. 6. CHRISTIANSEN H, et al. Nitroglycerin infusion; factors influencing the concentration of nitroglycerin available to the patient. J. Clin. Hosp. Pharm., 1980, 5, 209-215. 7. COTE D, et al. Nitroglycerin adsorption to polyvinylchloride seriously interferes with its clinical use. Anesth. Analg. (Cleve), 1982, 61, 541-543.

mode of infusion in bone marrow transplant patients. Bone Marrow Transplantation, March 2000; 25, (6): 633-638. 23. Takakura K, et al. Adsorption of lidocaine into a plastic infusion balloon. Anesthesia & Analgesia, 2000; 91: 192-194. 24. Kambia NK et al. Compatibility of nitroglycerin, diazepam and chlorpromazine with a new multilayer material for infusion containers. February 2005; Journal of Pharmaceutical and Biomedical Analysis, 37, 2, (23): 259-264.

8. LEE M. G. et al. Absorption of isosorbide dinitrate by PVC infusion bags and administration set. J. Clin. Hosp. Pharm., 1981, 6, 209-211.

25. MacKichan J, Duffner PK, Cohen ME. Adsorption of diazepam to plastic tubing. N Engl J Med 1979; 301: 332–3.

9. REMON J. P., BOGAERT M. G. Loss of glyceryl trinitrate and of isosorbide dinitrate during infusion, a literature survey and practical recommendations. Pharm. Hosp.

26. Banker G, Rhodes T. Modern Pharmaceutics. 2002; Protectants: 592.

France., 1984, 69, 25-28. 27. Schildt B, Ahlgren T, Berghem L, Wendt Y. Adsorption of insulin by infusion materials. 10. Florence A, Attwood D. Physicochemical Principles of Pharmacy. 2006; 5: 173. 11. Palmgrén J, Mönkkönen J, Korjamo T, Hassinen A. and Seppo Auriola. Drug adsorption to plastic containers and retention of drugs in cultured cells under

Acta Anaesthesiology Scandinavia, 1978; 22: 556-562. 28. Hans P, Paris P, Mathot F. Intravenous nitroglycerin perfusion techniques: clinical implications. Intensive Care Medicine, 1982; 8: 93-95.

in vitro conditions. European Journal of Pharmaceutics and Biopharmaceutics, November 2006; 64, (3): 369-378.

29. Barann M, et al. Loss of propofol during in vitro experiments. Anesthesiology 2000; 93: 310-311.

12. Allen L, Popovich N, Ansel H. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 2005; 15: 499-500. 13. Thompson JE, Davidow LW. A Practical Guide to Contemporary Pharmacy Practice. 2003; 34: 21. 14. Smith C, et al. Leakage and absorption of isoflurane by different types of anaesthetic circuit and monitoring tubing. Anaesthesia 2002; 57: 686-689. 15. Unger JK, et al. Adsorption of xenobiotics to plastic tubing incorporated into dynamic in vitro systems used in pharmacological research — limits and progress.

30. Allwood M, Stanley A, Wright P. The Cytotoxics Handbook, 2002, Biologicals: 447. 31. Shader, et al. It’s in the Bag: Drug Absorption by Drug-Delivery Systems. October 1997; Journal of Clinical Psychopharmacology. 17, (5): 339-340. 32. Medsafe. Nimotop general information. 2007. [Online] URL http://www.medsafe. govt.nz/profs/Datasheet/n/nimotoptabinf.htm [Accessed on 1st February 2008] 33. Smith JC et al. Uptake of drugs by catheters: the influence of the drug molecule on sorption by polyurethane catheters. 1996; Biomaterials, 17, (15): 1469-1472.

Polymer Contents, August 2001; 18, (8): 583-586. 16. Ko J and Odegaard L. Chlorine-Free Blends for Flexible Medical Tubing. Cockrell School of Engineering, 1997 [Online]. URL http://www.engr.utexas.edu/ethics/ design/medicaltubing.cfm [Accessed on 1st February 2008] 17. Larson S. Internal report on evaluation of drug adsorption with PVC and blend tubing. 3M, 1995. 18. Kaul A, et al. A Review of Possible Toxicity of DEHP. Drug Intelligence & Clinical

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SECTION 7 - MRI Study Is Bionector suitable for use with MRI scanners ?

SECTION 7 - MRI testing definitions

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According to new terminology developed by The Magnetic Resonance task group of the American Society for Testing and Materials (ASTM) International, Bionector is classified as MR Conditional based on testing and definitions contained in ASTM F2503-05.

A summary of the findings is as follows: 1. 2. 3.

No magnetic attraction (no movement) 0.5 degrees C temperature rise Image distortion at and immediately surrounding the device

The ASTM use the following three categories to define devices which may be exposed to MR: MRI Safe MRI Conditional MRI Unsafe

New Terminology with Regard to Magnetic Resonance Imaging (MRI) and Implants and Devices “Old” Terminology The terminology applied to implants and devices relative to the MRI environment has evolved over the years. In 1997, the Food and Drug Administration, Center for Devices and Radiological Health, proposed definitions for the terms “MR Safe” and “MR Compatible” (1) . These terms are defined as follows: • MR Safe: The device, when used in the MRI environment, has been demonstrated to present no additional risk to the patient or other individual, but may affect the quality of the diagnostic information. The MRI conditions in which the device was tested should be specified in conjunction with the term MR safe since a device which is safe under one set of conditions may not be found to be so under more extreme MRI conditions. • MR Compatible: A device shall be considered “MR compatible” if it is MR safe and the device, when used in the MRI environment, has been demonstrated to neither significantly affect the quality of the diagnostic information nor have its operations affected by the MR system. The MRI conditions in which the device was tested should be specified in conjunction with the term MR safe since a device which is safe under one set of conditions may not be found to be so under more extreme MR conditions. Using this terminology, MRI testing of an implant or object involved assessments of magnetic field interactions, heating, and, in some cases, induced electrical currents while MR compatibility testing required all of these as well as characterisation of artefacts. In addition, it may have been necessary to evaluate the impact of various MRI conditions on the functional or operational aspects of an implant or device (2).

“New” Terminology Over the years, manufacturers generally used the terms “MR safe” and “MR compatible” to label medical devices. However, in time it became apparent that these terms were confusing and were often used interchangeably or incorrectly (3). Therefore, in an effort to clarify the terminology and, more importantly, because the misuse of these terms could result in serious accidents for patients and other individuals, the MR task group of the American Society for Testing and Materials (ASTM) International developed a new set of terms with associated icons (4).The new terms, MR Safe, MR Conditional, and MR Unsafe are defined by the ASTM document, as follows.

SECTION 7 - MRI testing definitions

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• MR Safe: An item that poses no known hazards in all MRI environments. Using the new terminology, “MR safe” items include nonconducting, non-metallic, non-magnetic items such as a plastic Petri dish. An item may be determined to be MR Safe by providing a scientifically based rationale rather than test data. • MR Conditional: An item that has been demonstrated to pose no known hazards in a specified MRI environment with specified conditions of use. Field conditions that define the MRI environment include static magnetic field strength, spatial gradient, dB/dt (time varying magnetic fields), radio frequency (RF) fields, and specific absorption rate (SAR). Additional conditions, including specific configurations of the item (e.g., the routing of leads used for a neurostimulation system), may be required. For MR Conditional items, the item labelling includes results of testing sufficient to characterise the behavour of the item in the MRI environment. In particular, testing for items that may be placed in the MRI environment should address magnetically induced displacement force and torque, and RF heating. Other possible safety issues include but are not limited to, thermal injury, induced currents/voltages, electromagnetic compatibility, neurostimulation, acoustic noise, interaction among devices, and the safe functioning of the item and the safe operation of the MR system. Any parameter that affects the safety of the item should be listed and any condition that is known to produce an unsafe condition must be described. • MR Unsafe: An item that is known to pose hazards in all MRI environments. MR Unsafe items include magnetic items such as a pair of ferromagnetic scissors. In addition to the new terms, the ASTM document introduced corresponding icons, consistent with international standards for colours and shapes of safety signs. The icons are intended for use on items that may be brought into or near the MRI environment as well as in product labelling. The icons may be reproduced in colour or in black and white, however the use of colour is encouraged because of the added visibility. The “MR Safe” icon consists of the letters ‘MR’ in green in a white square with a green border, or the letters ‘MR’ in white within a green square. The “MR Conditional” icon consists of the letters ‘MR’ in black inside a yellow triangle with a black border. The “MR Unsafe” icon consists of the letters ‘MR’ in black on a white field inside a red circle with a diagonal red band. For MR Conditional items, the item labelling must include results of testing sufficient to characterise the behaviour of the item in the MRI environment.

Use of Terminology The new terminology is intended to help elucidate matters related to biomedical implants and devices in order to ensure the safe use of MRI technology. Importantly, it should be noted that this new terminology is not being applied retrospectively to implants and devices that previously received Food and Drug (FDA) approved labelling using the terms “MR safe” or “MR compatible” (i.e. in general, this applies to those objects tested prior to December, 2005). Accordingly, this should be understood to avoid undue confusion regarding the matter of labelling for “older” vs. “newer” implants.

SECTION 7 - MRI testing definitions

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References (1) United States Food and Drug Administration, Center for Devices and Radiological Health, A Primer on Medical Device Interactions with Magnetic Resonance Imaging Systems. http://www.fda.gov/cdrh/ode/primerf6.html, 1997. (2) Shellock FG. Reference Manual for Magnetic Resonance Safety Implants and Device: 2007 Edition. Biomedical Research Publishing Group, Los Angeles, CA, 2007. (3) Shellock FG, Crues JV. Commentary: MR Safety and the American College of Radiology White Paper. American Journal of Roentgenology 2002;178:1349-1352. (4) American Society for Testing and Materials (ASTM) International, Designation: F2503-05. Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic Resonance Environment. ASTM International, West Conshohocken, PA, 2005.

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SECTION 8 - Directions for Use

DB BION 13 196 E - 10/17

CRITICAL CARE For further information, please contact: questions@vygon.com The specifications given in this brochure are for information only and are not, under any circumstances, of a contractual nature.

VYGON - 5, rue Adeline - 95440 ECOUEN - FRANCE Customer service - Tel : + 33 (0)1 39 92 64 15 - Fax : + 33 (0)1 34 29 19 34 w w w. v y g o n . c o m