FREQUENTLY ASKED QUESTIONS AND REFERENCE GUIDE

Transcription

1 FREQUENTLY ASKED QUESTIONS AND REFERENCE GUIDE

2 erapid Nebulizer System: FAQ s for the CF Care Team Important: Please refer to the erapid Nebulizer System Instructions For Use for complete instructions. TABLE OF CONTENTS A. Product Description & Indication for Use B. eflow Technology Comparison C. Device Performance D. Operation: Taking a Treatment E. Components & Compatibility with other eflow Technology Devices F. Medication & Prescribing Information G. ebase Controller H. Handset & Accessories I. Cleaning & Disinfection J. Troubleshooting & Warranty Information K. Cost, Insurance Coverage, & Reimbursement L. Data & Studies Exhibit A: Sample Letter of Medical Necessity PAGE

3 A. Description & Indication For Use 1. What is the indication for use for the erapid Nebulizer System? The erapid Nebulizer was 510(k) cleared to market in May 2012 for patients for whom doctors have prescribed medication for nebulization. It is intended for adult and pediatric patients, and may be used in hospitals, hospital-type facilities, nursing homes, sub-acute institutions and home environments. Please refer to the erapid Nebulizer System instructions for use for a complete guide to operation, troubleshooting, warnings and precautions. The efficiency of the erapid Nebulizer System has been designed to accommodate use with currently approved and marketed nebulizer drugs (it is less efficient, by design, than say Altera). Compared to drug-specific nebulizer handsets (i.e. - Altera), erapid Nebulizer Handset has a 1 ml compartment (see image) built in to mimic the residual volume typically seen with jet nebulizers. In addition, the erapid Nebulizer Handset utilizes a small aerosol chamber that further aligns the delivery performance with that of the LC PLUS jet nebulizer. The key difference is that the nebulization time of the erapid Nebulizer System is cut by one-half compared to the nebulization time of a jet nebulizer. 2. What is the erapid Nebulizer System? The erapid Nebulizer System is a general-purpose nebulizer and part of the eflow Technology platform of electronic nebulizers which use a vibrating membrane to generate aerosol. This membrane is perforated with several thousand laser-drilled holes. A piezoelectric actuator causes the membrane to vibrate 117,000 times per second (117 Kz) creating an alternating pressure field, which forces the medication through the holes and generates a fine, dense aerosol. The aerosol is suspended in a patented valved aerosol chamber until the patient inhales. 7. What is the maximum fill volume of the erapid Nebulizer? The erapid Nebulizer maximum fill volume is 6 ml. 3. What is eflow Technology? eflow Technology is the platform which offers a range of highly efficient electronic nebulizer systems, all of which utilize vibrating membrane technology to generate aerosol, provide short nebulization times with silent operation and better portability for patients. Each configuration delivers drug to the lower respiratory tract. Altera, eflow rapid, erapid, investigational eflow, and Trio are all part of the eflow Technology platform. 8. What is the minimum fill volume of the erapid Nebulizer? The erapid Nebulizer minimum fill volume is 2 ml. 9. What is included with the erapid Nebulizer System? Carrying Case, ebase Controller, 2 erapid Nebulizer Handsets, Nebulizer Connection Cord, AC Power Supply, 4 AA Batteries, Instructions for Use & Warranty Card 4. Is there a minimum age that can use the erapid Nebulizer System? The erapid Nebulizer System is best suited for patients aged two and above that can take treatments in an upright position. The erapid Nebulizer System should not be used with those that cannot sit upright such as infants and babies. 2 erapid Nebulizer Handsets 5. What is the eflow rapid? ebase Controller The eflow rapid is the brand name that is used for the erapid Nebulizer System outside of the US and Canada. Both devices are identical. eflow rapid was first launched in Europe in 2005 primarily for the CF population where it has gained wide acceptance and use in the CF community. 6. How does the general-purpose erapid Nebulizer System compare to the drug-specific Altera Nebulizer System? Carrying Case Four AA Batteries Nebulizer Connection Cord Altera is a drug-specific nebulizer handset designed and tested exclusively in clinical trials with Cayston. Cayston and Altera have mutually conforming labels that bind drug and device together. The Altera nebulizer handset is significantly more efficient than a standard jet nebulizer and the erapid Nebulizer System. The Altera nebulizer delivers virtually the entire drug dose that is loaded into it. It has a negligible residual volume which means that if unapproved drugs such as albuterol, hypertonic saline, dornase alfa and tobramycin, etc. are used in Altera, the drug would potentially be over-dosed. AC Power Supply 1 2

4 B. eflow Technology Comparison 2. What is the difference between the Altera and erapid aerosol heads and handset parts? 1. What are the differences between the erapid, Altera and Trio Nebulizer Systems that all utilize eflow Technology? eflow Technology Comparison US Market Altera erapid Nebulizer System Trio EFFICIENCY HANDSET Altera More efficient than a conventional jet nebulizer and erapid Nebulizer System.7 Large aerosol chamber size. Altera brand printed on the side of the aerosol chamber. erapid Nebulizer System In-vitro delivered drug doses comparable to LC PLUS jet nebulizer. Nebulization time 50-65% faster than a jet nebulizer.1 Small aerosol chamber size. erapid brand printed on the side of the aerosol chamber. INDICATION FOR USE The Altera Nebulizer System is intended specifically for the aerosolization of CAYSTON (aztreonam for inhalation solution) using vibrating membrane technology. The device is intended for adult and pediatric patients who have been prescribed CAYSTON, and may be used in hospitals, hospital-type facilities, nursing homes, sub-acute institutions and home environments. The erapid Nebulizer System is to be used with patients for whom doctors have prescribed medication for nebulization. It is intended for adult and pediatric patients, and may be used in hospitals, hospitaltype facilities, nursing homes, sub-acute institutions and home environments. The Trio Nebulizer System is to be used with patients for whom doctors have prescribed medication for nebulization. It is intended for adult and pediatric patients, and may be used in hospitals, hospitaltype facilities, nursing homes, sub-acute institutions and home environments. AEROSOL HEAD Etched with the brand name Altera Etched with the brand name erapid. RESIDUAL VOLUME Negligible residual volume. Delivers virtually all drug loaded. Do not use with medications other than Cayston. If a jet nebulizer drug is used with Altera over-dosing may occur. MAX. FILL VOLUME 4 ml 6 ml Approx. 1 ml, similar to the residual volume of general use jet nebulizers. DETAILS DRUG/DEVICE OPTIMIZATION DISTRIBUTION Drug Specific Nebulizer Highly efficient, targeted lung delivery. Low fill volume Negligible residual volume 2-3 minute nebulization time, encourages patient adherence Potential safety issue if used with unapproved drugs Device performance optimized to drug formulation and formulation optimized to device. Distribution controlled by the Drug Manufacturer via CF Specialty Pharmacies. Altera distributed only with prescription for Cayston. General Use Nebulizer Comparable drug delivery to LC PLUS jet nebulizer Reduces nebulization by 50-65% (depending on drug) Mimics residual volume of traditional jet nebulizers (approx. 1 ml) Studied in randomized clinical trial with Pulmozyme gained FDA approval for use in erapid in December Device not optimized to drug formulation. Device design independent of drug formulation. Distributed by a select group of Specialty Pharmacies. General Use Nebulizer Highly efficient, one component of a CF management program at discretion of the prescribing physician. Negligible residual volume Medication dose determined without benefit of safety or efficacy data Not studied in randomized clinical trials Device not optimized to drug formulation. Device design independent of drug formulation. Limited distribution by Specialty Pharmacies. INDICATION Drug specific, Cayston only. General purpose, indicated for use with multiple medications per discretion of prescriber. Not for use with Cayston. 3. Why does erapid Nebulizer System have a small aerosol chamber and the Altera have a large chamber? The aerosol chamber s function is to accumulate aerosol during exhalation so that a bolus of medication is delivered during inhalation and medication waste is minimized. The size of the aerosol chamber directly correlates to the device s efficiency and lung deposition. The erapid Nebulizer System has a small aerosol chamber because its efficiency has been designed to match the aerosol delivery of the LC PLUS jet nebulizer, but the nebulization time with erapid Nebulizer System is reduced by 50-65%. 1 The Altera Nebulizer System has a large size aerosol chamber. A greater volume of aerosol accumulates in the larger chamber and is available for inhalation to the lungs. Combined with a negligible residual volume (virtually all drug volume is nebulized); the drug-specific Altera nebulizer for the exclusive delivery of Cayston, is significantly more efficient than the erapid Nebulizer System with a small aerosol chamber and a 1 ml residual volume. 4. What is the difference between erapid (eflow Technology) and a traditional ultrasonic nebulizer? The erapid provides a gentle mode of nebulization compared to traditional ultrasonic nebulizers. Ultrasonic nebulizers work with a much higher frequency which is applied directly to the medication and results in higher temperatures and physical stresses to the drug which may damage certain drugs such as Pulmozyme (DNase) and budesonide. 3 4

5 C. Device Performance D. Operation: Taking a Treatment 1. What are the performance characteristics of the erapid Nebulizer System? TOTAL OUTPUT RATE: 500 mg/min MMD (MASS MEDIAN DIAMETER): 4.1 µm MASS PERCENTAGE BELOW 5µm: 64% 1. What is the proper way to administer a treatment with the erapid Nebulizer System? Please refer to Section G, pg. 10 of the erapid Nebulizer System Instructions for Use (IFU) for complete instructions on how to take a treatment with the erapid Nebulizer System. 2 The erapid Nebulizer Handset should be held level. If held > 45 degrees up or down, the handset will emit 2 beeps; the status light on the Controller flashes 2 green lights. After approximately 30 seconds the Controller will shut off. The Controller will signal 2 beeps and the Dose Complete screen appears when the dose is delivered and the treatment is complete Isn t the erapid Nebulizer System more efficient than a jet nebulizer? The performance of the erapid Nebulizer System is designed to match the aerosol delivery of the LC PLUS jet nebulizer but with significantly faster delivery times. The erapid nebulizer was designed to retain approximately 1 ml of drug which is similar to residual volume left in traditional jet nebulizers. 3. What is the nebulization time for commonly used nebulizer medications with the erapid Nebulizer System compared to a jet nebulizer? 1,5 2. What is the Pause Function? Please refer to the erapid Nebulizer System instructions for use for complete information. The ebase Controller includes software that allows a PAUSE, when necessary. If for any reason the treatment must PAUSE before its completion, press and hold the Controller s On/Off Button for one full second. The PAUSE mode is activated when the LED flashes GREEN and the ebase Controller display switches from the TREATMENT screen to the PAUSE screen. When treatment is ready to resume, press and hold the Controller On/Off Button for one full second. The treatment will then resume, with the Controller display switching from the PAUSE screen to the TREATMENT screen. 2 Active Agent/ Concentration Substance/ Class Nebulization Time (min.)standard Jet Nebulizer/ Compressor Nebulization Time (min.)erapid Nebulizer System PAUSE SCREEN (Battery) PAUSE SCREEN (AC Adapter) Dornase Alpha (Pulmozyme) 2.5 mg/ 2.5 ml erapid and LC PLUS are on label for Pulmozyme Hypertonic saline solution (Hypersal ) 7%/ 4ml Mucolytic Agent DNA cleaving enzyme Hydrator How will the patient know when to end the treatment? The Controller will automatically turn off at the end of the treatment. The Controller will signal 2 beeps and the Dose Complete screen appears. 2 Salbutamol 2.5 mg/ 2.5 ml Bronchodilator Beta2 -agonist

6 4. How much medication should be left in the Medication Reservoir at the end of the treatment? Following treatment only about 1 ml (1/5 teaspoon) of medication should be remaining in the Medication Reservoir. If more than 1 ml remains (see image), put the Medication Cap back on and restart the treatment. Following treatment, clean the Aerosol Head. 2 E. Components & Compatibility with Other eflow Technology Devices 1. What are the components of the erapid Nebulizer System? 5. Does the erapid Nebulizer Handset need to be cleaned between each medication in a sequential treatment session? The erapid Nebulizer System IFU states that the handset needs to be cleaned between each treatment. However in a sequential treatment session and at the discretion of the HCP, an alternate method may be recommended such a rinsing with sterile water between medications. 6. Do separate handsets need to be used for each medication? No. The erapid Nebulizer System comes with two handsets, so that patients may alternate between them if they choose. 2. What are the components of the erapid Handset? 7 8

7 3. What are the replaceable components of the erapid Nebulizer System? The erapid Nebulizer Handset should be replaced periodically. Please refer to Section H in the erapid Instructions for Use for general guidelines on when to replace the erapid Handset. 4. What are the durable components of the erapid Nebulizer System? The ebase Controller, Nebulizer Connection Cord and AC Power Supply are the durable components of the erapid Nebulizer System and covered under a limited 2-year warranty. 5. What components are compatible between the Altera and the erapid Systems? The interchangeable components within the erapid and Altera nebulizer systems are the ebase Controller, Nebulizer Connection Cord, AC Power Supply and Medication Cap is compatible. The Nebulizer Handset and Aerosol Head are not interchangeable. 6. Can the erapid Nebulizer System be used with a ventilator? No. The erapid Nebulizer System cannot be used with a ventilator; it is not indicated or designed to work with a ventilator. There s no adaptor and the pressure from the ventilator will cause leaks in the nebulizer system. F. Medication & Prescribing Information 1. What medications can be nebulized with the erapid Nebulizer System? The erapid Nebulizer is a nebulizer for use in patients for whom doctors have prescribed medication for nebulization What medications are specifically approved by the FDA for use with the erapid Nebulizer System? Pulmozyme is FDA approved for use with the erapid Nebulizer System. The erapid Nebulizer System is a general-purpose nebulizer. Both the erapid Nebulizer System and traditional jet nebulizers are intended for general use with currently approved nebulized medications at the discretion of the prescribing clinician. 3. If only Pulmozyme is approved by FDA with the erapid Nebulizer System, why aren t other nebulized medications FDA approved with the erapid Nebulizer System? Pulmozyme is approved with the erapid Nebulizer System. 6 However, the erapid Nebulizer System is a general-purpose nebulizer and can be used with medications prescribed by a physician or HCP, much like the LC PLUS jet nebulizer which is FDA cleared as a general purpose nebulizer. 4. What type of patient could benefit from the erapid Nebulizer System? Any patient that has a significant treatment burden that uses multiple nebulizer medications daily and may have difficulty managing their regimen or misses required nebulizer treatments. Also, any patient that uses Pulmozyme may benefit from nebulizer therapy with the erapid Nebulizer System. 5. What information should be included in a prescription for the erapid Nebulizer System? Patient Name, Address, Date of Birth Patient Diagnosis Code Product: erapid Nebulizer System or erapid Nebulizer Handset Documented Need and Use of erapid 6. What information should be included in a Letter of Medical Necessity? Please refer to Exhibit A for an erapid Sample Letter of Medical Necessity 9 10

8 G. ebase Controller 1. What is the expected life of the ebase Controller? The durable components of the erapid Nebulizer System include the ebase Controller, the Nebulizer Connection Cord, and the AC Power Supply, which are all covered under a two year limited warranty. The Controller may last from 3-5 years. 2. If my patient already has an ebase Controller, will it work with the erapid Handset? H. Handset & Accessories 1. How long will the erapid Handset last? The erapid Handset may last up to six months with moderate usage, proper cleaning, disinfection and use of the Easycare cleaning aide. Duration of use may decrease when using multiple drugs or if the handset is not properly cared for according to the erapid Nebulizer System IFU. Performance over repeated use can deteriorate quickly depending on which drugs are used, how many per day, the patient s cleaning/disinfection habits, etc. Even with proper care, it is expected that nebulization time will gradually increase over the lifetime of the handset. If the patient already has an ebase Controller, the erapid Handset is compatible and will work with it. The ebase Controller is not 510(k) cleared to market to use with TRIO Nebulizer Handsets and should not be used. 3. Will using a handset, other than the one that came with the ebase Controller void the warranty? PARI provides a 2-year Limited Warranty on the ebase Controller assuming the erapid or Altera Nebulizer Handset is used. PARI s warranty will not be voided if the ebase Controller is used with other Altera or erapid Nebulizer Handsets. The ebase Controller is not 510(k) cleared to market to use with TRIO Nebulizer Handsets and should not be used. 4. Do all ebase Controllers come with the Pause Function? The Pause function feature has been available since 2012 in the erapid ebase Controller and since 2013 with the Altera ebase Controller. If an Altera ebase Controller was obtained prior to 2013, then it will not have the Pause function feature. 5. How durable is the device? For example, if a patient kept the device in their backpack or suitcase while traveling, how long would it last? All eflow Technology nebulizer systems undergo survivability, durability, drop testing and user testing as required by the FDA 510(k) process. Please see Section H in the erapid Instructions for Use for guidance on nebulizer handset replacement. The Controller may last up to 3-5 years. 8 Batteries and AC Power Supply for the ebase Controller 6. How long will a new set of batteries last? A new set of batteries will provide approximately 2 hours of continuous treatment. Patients may consider using rechargeable batteries How is the AC Power Supply used? The AC Power Supply is useful as a backup when the battery supply is depleted. It can be used with V outlets and will adjust automatically to incoming voltage. It can be used worldwide, but does require plug convertors Why does Genentech have different recommendations for replacement of the erapid Nebulizer Handset with Pulmozyme? Genentech s recommendation is based on simulated in-vitro usage data that were submitted to FDA to get Pulmozyme approved for use with erapid Nebulizer System. Because the data included a maximum of 90 uses, the FDA limited the erapid nebulizer handset to 90 uses with Pulmozyme. Please contact Genentech for questions regarding extended usage. PARI has simulated usage data to support up to six months use with eflow Technology. 8 Therefore, PARI s recommendation continues to be up to six months duration with moderate usage, proper cleaning, disinfection and use of the Easycare cleaning aide. Handset longevity will decrease when using multiple drugs or if the handset is not properly cared for according to the erapid Nebulizer System IFU. Performance over repeated use can deteriorate quickly depending on which drugs are used, how many per day, the patient s cleaning/disinfection habits, etc. 3. What masks should be used with the erapid Nebulizer System? The Smartmask Kids Mask is available for use with the erapid Nebulizer System. It fits children ages 2 years and above. The Smartmask Kids is a close-fitting, soft mask with an exhalation valve that is designed to work with the inspiration valve in the aerosol chamber of the erapid Nebulizer System. The exhalation valve of the mask works together with the inhalation valve of the nebulizer handset Can Bubbles the Fish Mask be used with erapid Nebulizer System? No. Bubbles the Fish mask is not suitable for use with the erapid Nebulizer System. The erapid Nebulizer System requires the use of a close-fitting valved mask to enable the opening of the erapid s valved aerosol chamber. 5. Can the PARI Baby Mask be used with the erapid Nebulizer System? No. Although the PARI Baby Mask is a close fitting mask, it is not suitable for use with the erapid Nebulizer System because it lacks the required valve system to work with the erapid valved aerosol chamber. The erapid Nebulizer System requires the use of a close-fitting valved mask to enable the opening of the erapid s valved aerosol chamber to deliver the prescribed medication. 6. Can the PARI PEP S device be used with the erapid Nebulizer System? No. The PEP S is not recommended with erapid Nebulizer System. The pressure that is produced with the PEP S when blowing against a resistance may cause the flaps on the inspiratory valve located in the aerosol chamber to push through in the incorrect position

9 I. Cleaning & Disinfection 1. What cleaning methods are recommended for the erapid Nebulizer System? Please refer to pages 12 & 13 of the erapid Nebulizer System Instructions for Use for complete cleaning & disinfection instructions. Cleaning the erapid Handset according to the IFU will help maintain its longevity and preserve nebulization time. 2 The handset should be cleaned as soon as possible after treatment. The handset should be cleaned after each use, disassembled and soaked for 5 minutes with liquid dish detergent in a wash basin. Avoid white or antibacterial liquid dish soaps that contain additives that may harm the aerosol head How soon after treatment does the nebulizer handset need to be cleaned? The erapid Nebulizer Handset should be cleaned as soon as possible after treatment What disinfection methods are recommended for the erapid Nebulizer System? Please refer to page 14 of the erapid Nebulizer System Instructions For Use for complete disinfection instructions. 2 The following disinfection methods are the only methods that have been validated and FDA 510(k) cleared. 2 The handset parts should be disinfected with one of the following methods at the end of each treatment day. Boiling in DISTILLED water for 5 minutes in a clean pot Commercially available medical device disinfectant such as Control III. (Please note the CFF Infection Control Guidelines do not recommend this method). 4. Why is DISTILLED water required in the boiling method for disinfection? Distilled water is needed because hard water and/ or minerals in tap water can damage the aerosol head The erapid Nebulizer System instructions state to rinse with tap water after cleaning. Is it acceptable to rinse the nebulizer handset parts with sterile water after cleaning? The cleaning, disinfection interval and frequency is determined by PARI. 8 If the HCP has concerns, more frequent disinfection and rinsing with sterile water is acceptable and at the discretion of the HCP. 7. We recommend a disinfection method other than what is listed in PARI s instructions (i.e.- steam sterilizer). What should we recommend to patients? The cleaning and disinfection methods in the erapid Instructions for Use are the only ones that PARI can advocate based on testing and FDA clearance for erapid Nebulizer System. However, if alternate methods are preferred, they can be recommended at the discretion of the health care provider. 8. Why do PARI s cleaning/ disinfection instructions differ from that of the Cystic Fibrosis Foundation infection control guidelines? The cleaning and disinfection methods in the erapid Nebulizer System Instructions for Use are the only ones that PARI can advocate based on testing and FDA clearance for the erapid Nebulizer System. If alternate methods are preferred, they can be recommended at the discretion of the health care provider. 9. Can the erapid Handset be sterilized by a hospital or clinic? Yes. Hospitals and clinics can sterilize the erapid Nebulizer Handset parts by wet autoclaving at 250 F (121 C) for 30 minutes. Follow the autoclave manufacturer s instructions for use. 2 easycare Cleaning Aide 10. What is the easycare cleaning aide? The easycare cleaning aide is used to clean and unclog the microscopic holes in the Aerosol Head by reversing the flow of liquid (backwash). The easycare should be used no more than twice a week to maintain proper nebulization time. The Aerosol Head should not be used with easycare more than 25 times over its duration of use When should the easycare be used? Cleaning with the easycare is recommended if the nebulization time for the same fill volume of a given medication significantly increases. The FUNCTIONALITY TEST described in Section K page 15, in the erapid Nebulizer System Instructions for Use can help determine when use of easycare is indicated Does the easycare need to be cleaned and disinfected? easycare should be cleaned according to the easycare Instructions for Use (IFU). The aerosol head needs to be disinfected after using easycare using a disinfection method described in the erapid IFU. 2,4 6. Will the tap water rinse contaminate the nebulizer and cause bacterial growth before the next treatment, which is administered before disinfection at the end of each treatment day? There is no data looking at bacterial counts in between cleaning and disinfection. Bio-burden testing is required by FDA and was performed for cleaning and disinfection to determine overall bacterial eradication. Cleaning works very well and disinfection further decreases the bacterial load. The cleaning, disinfection interval/frequency is determined by PARI. 8 If there are concerns, more frequent disinfection and rinsing with sterile water are acceptable at the discretion of the HCP

10 J. Troubleshooting & Warranty Information K. Cost, Insurance Coverage, & Distribution 1.What support is available to help troubleshoot the erapid Nebulizer System? Refer to Section L: Frequently Asked Questions and Troubleshooting Guide that can be found in the erapid Nebulizer System instructions for use on page 15. Please contact PARI Customer Care at FAST.NEB if the issue cannot be resolved using the steps found in the troubleshooting Guide. 2 2.Why is the nebulization time getting longer? As a normal part of wear, it is likely that the nebulization time of the handset will gradually increase over the period of use. However, it is important that the aerosol head be cleaned regularly according to the erapid Nebulizer System Instructions For Use (IFU) to maintain a fast nebulization time. A Functionality Test can be performed to determine if it is time to replace the handset in view of a long nebulization time that is not corrected by cleaning the aerosol head or using easy care. Please refer to Section K, pg. 15 in the erapid Nebulizer System IFU for more information Does the erapid Nebulizer System have a warranty? PARI provides a 2-year Limited Warranty on the durable components (ebase Controller, Nebulizer Connection Cord, AC Power Supply). The patient needs to register by phone, mail, or on-line. Warranty registration details are included on the erapid Nebulizer System Warranty Card. 9 There is no warranty on the erapid Handset except for out of box failures (first use). Cost What is the cost of the erapid Nebulizer System? Please check with the specialty pharmacy distributors for pricing as insurance coverage and patient out of pocket costs vary. Insurance Coverage Is the erapid Nebulizer System covered by insurance? Payer coverage and patient out-of-pocket costs vary by plan and may change over time. Currently, some payers may cover or have partially covered the erapid Nebulizer Handset or the erapid Nebulizer System through a prior authorization with a statement of medical necessity. The specialty distributors (SP s) will work with insurance providers on behalf of patients to determine if insurance will cover the erapid Nebulizer System. Distribution Who distributes the erapid Nebulizer System? The erapid Nebulizer System is available through a network of select special distributors (SP s) listed below. Check PARI s website for the most current list at: Can patients without CF be referred to SP s for availability of erapid Nebulizer System? Please check with the specialty pharmacy distributors listed on our website

11 L. Data & Studies What studies or data are available with erapid Nebulizer System? eflow Rapid/ erapid Reference List 1. S. Seemann, M. Hug, R. Lichtinghagen, A. Schmitt, M. Tservistas, R. Waldner, and M. Knoch. Improving Aerosol Drug Delivery in CF therapy. 28th European Cystic Fibrosis Conference, Crete, Greece, June 22th - 26th, Manfred Keller, Albert Bucholski, Stefan Seemann, Michael Hug, Andreas Schmitt, and Martin Knoch. Reduction in nebulisation time of aqueous drug solutions by the eflow rapid in comparison to a jet nebuliser to improve patient convenience and compliance. European Respiratory Society Annual Congress, September 17-21, 2005, Copenhagen, Denmark. 3. S. Naehrig, S. Lang, H. Schiffl, R. M. Huber, R. Fischer. LUNG FUNCTION IN ADULT PATIENTS WITH CYSTIC FIBROSIS AFTER USING THE EFLOW RAPID FOR ONE YEAR. Eur J Med Res (2010) 15: Reychler G, Lebecque P, Knoop C, Opdekamp C. SATISFACTION SURVEY CONCERNING VIBRATING MESH-NEBULIZERS IN CF PATIENTS. Journal of Cystic Fibrosis vol. 6 June, p. S Rottier BL, van Erp CJP, Sluyter TS, et al. Changes in performance of the Pari eflow rapid and the Pari LC Plus during 6 months of use by CF patients. J Aerosol Med Pulmon Drug Deliv 2009;22: Bakuridze L, Andrieu V, Dupont C, et al. Does repeated disinfection of the e-flow rapid nebulizer affect in vitro performance? J Cystic Fibros 2007;6: Hubert D, Leroy S, Dominique S, Kovarik J. Pharmacokinetic comparison of inhaled tobramycin (TOBI ) via PARI eflow rapid or PARI LC Plus nebulizers in cystic fibrosis patients. European Cystic Fibrosis Conference Guy et al. Serum tobramycin levels following delivery of tobramycin (Tobi ) via eflow advanced nebuliser in children with cystic fibrosis. Journal of Cystic Fibrosis 9 (2010); Konstan M, Chou W, Xui Y, Trzakoma B, Sawicki G. IMPART Study Results: A Phase 4 Study in Patients With Cystic Fibrosis to Evaluate the Comparable Efficacy and Safety of Pulmozyme Delivered by the erapid Nebulizer System. North American Cystic Fibrosis Conference, Salt Lake City Utah, Geller D. The erapid Nebulizer for the Delivery of Inhaled Therapies for CF. Cystic Fibrosis Foundation White Paper. January THOMAS SCHERER, DAVID E. GELLER, LAURA OWYANG,MARCUS TSERVISTAS,MANFRED KELLER, NORBERT BODEN,KENNETH C. KES- SER, STEVEN J. SHIRE. A Technical Feasibility Study of Dornase Alfa Delivery with eflow Vibrating Membrane Nebulizers: Aerosol Characteristics and Physicochemical Stability. Journal of Pharmaceutical Sciences, Vol. 9999, 1 12 (2010). 6. Laurent Pitance, P.T.,Laurent Vecellio, Ph.D.,Teresinha Leal, Ph.D. Gregory Reychler, Ph.D.,Herve Reychler, M.D.,and Giuseppe Liistro. Delivery Efficacy of a Vibrating Mesh Nebulizer and a Jet Nebulizer under Different Configurations. JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY Volume 23, Number 6, Keller M, Brendel E, Luithlen A, Bruendl K, Mueller D, Tservistas M, Schierholz J, Denk O: Investigation of Colifin, 1 and 2 million I.U. Colistimethate Sodium (CMS) for aerosolisation in the eflow rapid and PARI LC SPRINT nebuliser. 33rd ECFS Conference, Valencia, Spain, June 16 19, J Cyst Fibros 2010, 9 (Suppl 1), S Bitterle E, Seemann S, Denk O, Wolf R, Keller M: Aerosol characterization of hypertonic saline (MucoClear 6%) in the eflow rapid nebulizer. 10. Deutsche Mukoviszidose Tagung, November 9 10, 2007, Würzburg, Germany. 9. Keller M, Hug M, Bitterle E, Bucholski A: Reduced Treatment Time for Colistimethate Sodium Solution (Colistin CF) Aerosolised by eflow rapid, a Novel Electronic Nebuliser. 29th European CF Conference, Copenhagen, Denmark, June 15 18, 2006 (poster and oral presentation). J Cyst Fibros 2006, 5 (Suppl. 1), S Knoch M, Keller M. OPTIMISING DRUG AND DEVICE TOGETHER FOR NOVEL AEROSOL THERAPIES. OnDrug Delivery, Hubert D, Leroy S, Nove-Josserand R, et al. Pharmacokinetics and safety of tobramycin administered by the PARI eflow Rapid nebulizer in cystic fibrosis. J Cyst Fibro 2009;8: Govoni M, Poli G, Cicirello H, et al. Pharmacokinetics of tobramycin nebulizer solution 300mg/4ml (Bramitob ) administered by Pari eflow rapid vs. Pari LC Plus nebulizer in cystic fibrosis patients. Respiratory Drug Delivery 2012, pp Lenney W, Edenborough F, Kho P, Kovarik JM. Lung deposition of inhaled tobramycin with eflow Rapid/LC Plus jet nebulizer in healthy and cystic fibrosis subjects. J Cyst Fibros 2011;10: Elkins MR, Tingpej P, Moriarty CP, et al. Tolerability of hypertonic saline when delivered rapidly via the eflow Rapid nebulizer in subjects with cystic fibrosis. Pediatr Pulmonol 2006;Suppl 29:292 [abstract 243] 17 18

12 Exhibit A: Sample Letter of Medical Necessity erapid Nebulizer System <Insert Date> RE: <Patient Name> < Patient DOB:> Letter of Medical Necessity for the erapid Nebulizer System To Whom It May Concern: <Insert Patient Name>, a <age> year-old <gender> with a diagnosis of cystic fibrosis is followed by <Name> CF Center. As a standard of care for patients with cystic fibrosis and part of this patient s treatment plan, it is necessary for <him/her> to take <qty.> nebulized medications daily. <Name> will need to be on nebulized medications for the rest of <his/her> life which may increase in number as more secondary infections ensue as <he/she> ages. Currently, the patient takes Pulmozyme daily <list other medications, frequency>. This patient may deteriorate quickly and possibly require hospitalization without these medications. <Name> spends a significant amount of time each day administering <his/ her> inhaled medications. Because of this significant treatment burden, <he/she> was prescribed an erapid Nebulizer System. Administering inhaled medications quickly and efficiently will decrease the treatment time burden and encourage adherence with <his/ her> prescribed treatment plan. The main advantages of the erapid Nebulizer System: Matches the pulmonary delivery of the LC PLUS jet nebulizer, but significantly cuts medication nebulization time. 1 Encourages treatment adherence in CF by reducing the time required with traditional nebulizer therapy by 50-65%. 1 Lightweight, compact and portable. Operates quietly for discrete use. Pulmozyme is approved for use with the erapid nebulizer; treatment is completed in approximately 2-3 minutes. 1 This represents a significant time reduction from traditional nebulizer therapy which can take up to 10 minutes to administer Pulmozyme. 1 Patients can spend up to two hours or more doing their required aerosol therapy with traditional nebulizers. This system completes treatments in less than half that time, allowing them more time for a productive and healthy life. Please approve coverage for the erapid Nebulizer System. If you have any questions regarding this matter do not hesitate to contact our office. Sincerely, <Physician Name>, MD Director Adult Cystic Fibrosis Center <Institution> <Address> <City, State, Zip Code> References 1. Seemann S, Hug M, Lichtinghagen R, et al. Improving aerosol drug delivery in cystic fibrosis. 28th ECFC. Crete, Greece, June erapid Nebulizer System Instructions for Use. 178D1009. Rev B 10/12 3. Saiman L, Siegel JD, LiPuma JJ, et al. Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update. Infect Control Hosp Epidemiol 2014; 35: S1-S Easycare Instructions for Use. 078D1022. Rev B 6/14 5. Gallem T, Tservistas M, Uhlig M, et al. Effect of Facemask Design on Aerosol Delivery from an Electronic Nebulizer. Respiratory Drug Delivery 2008, Pulmozyme. US Prescribing Information. 12/ Altera Instructions for Use. 678D1004 Rev K 7/14 8. Data on File, PARI. 9. erapid Nebulizer System Warranty Card 178D0171 Rev B 5/13 All trademarks are property of their respective companies. 1. Seemann S, Hug M, Lichtinghagen R, et al. Improving aerosol drug delivery in cystic fibrosis. 28th ECFC. Crete, Greece, June

13 Touchspray made under license from the Technology Partnership plc. PARI RESPIRATORY EQUIPMENT, INC. TEL: FAST-NEB ( ) eflow, erapid, ebase, and Smartmask are registered trademarks of PARI Pharma GmbH. Pulmozyme is a registered trademark of Genentech, Inc PARI Respiratory Equipment, Inc. All rights reserved. 178D0203 Rev A 5-15