Attachment 8: Proprietary Name

MEMORANDUM

Date:	November 6, 2007
TO:	Franklin T. Stephenson, CSO, OBRR/DBA/RPMB, HFM-380 Elena Karnaukhova, Committee Chair, OBRR/DH/LBVB, HFM-343 Laurence Landow, MD, OBRR/DH/CRB, HFM-392
From:	Nancy Chamberlin, Pharm.D, Regulatory Review Officer, Advertising and Promotional Labeling Branch (APLB), Division of Case Management (DCM), HFM-602
Through:	Ele Ibarra-Pratt, RN, MPH, Branch Chief, APLB, DCM, HFM-602
Through:	Robert A. Sausville, Director, DCM, HFM-610
Subject:	Review of proposed proprietary name Voluven (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride infusion) (BN070012)

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Executive Summary:
APLB recommends that the proposed proprietary names, Voluven® be found Acceptable with Concerns at this time.

Background:
On February 28, 2007, Fresenius Kabi Deutschland GmbH submitted NDA for Voluven (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride infusion). The sponsor submitted a request for review of their proposed proprietary name on which was received in the CBER Document Control Room on October 5, 2007, and in APLB on October 5, 2007.

"Voluven®" has been registered as a trademark with the U.S. Patent and Trademark Office since April 9, 2002.

In the submission the sponsor states, "Based on the accumulated experience with this proprietary name in more than seven years of international marketing, it is not thought that the name misrepresents the efficacy or safety of the product or presents a potential to contribute to medication errors or to confusion in the marketplace". The sponsor's rationale for choosing the name is that the terms "Volu" is derived from "volume" as in plasma volume substitute and "ven" is derived from "vein" as in intravenous infusion.

Overview of the Proposed Indication, Dose, Dosage Form, Administration, and Storage Information: 
The proposed indication for Voluven is for treatment and prophylaxis of hypovolemia. Each 100 mL contains 6 g hydroxyethyl starch 130/0.4 in 0.9% sodium chloride infusion. It will be supplied as 500 mL flexible plastic intravenous solution container.

The initial Voluven dose of 10 to 20 mL will be infused slowly to observe for possible anaphylactoid reactions. The proposed Voluven daily dose and rate of infusion will depend on the patient's blood loss, on the maintenance or restoration of hemodynamics and on the hemodilution (dilution effect). The adult dose may be up to 50 mL /kg/day. Administration of the product requires close and continued observations by the healthcare provider.

Proposed Proprietary Name Evaluation:

1. False or Misleading [21 CFR 201.6 (a)]:

   The proposed proprietary name Voluven is not regarded to be false or misleading.

2. Fanciful [21CFR 201.10 (c)(3)]:

   The proposed proprietary name Voluven is not regarded to be fanciful. It does not appear to imply that the drug or ingredient has some unique effectiveness or composition beyond that supported by the data.

3. Similarity in Spelling or Pronunciation [21 CFR 201.10 (c) (5)]:

   Voluven may be confused with the proprietary name or the established name of a different drug because of similarity in spelling or pronunciation. Since, drug products are prescribed through written, verbal, and /or electronic orders, such forms of communication may lead to medication errors, particularly if proprietary and /or established names sound or look alike. Even when proprietary names are only slightly similar, overlapping product characteristics may create a greater potential for confusion. Products are listed in the table below from the highest to lowest potential for causing a medication error.

   APLB also has concerns with similar letters in the first part of a proprietary or established name because the prescriber's handwriting may become less legible at the end of the name making these names undistinguishable with sound-alike, look-alike names for products that already exist in the U.S. marketplace.

   There is a similarity in spelling and pronunciation with proprietary names for other marketed products:

   • Marketed products like Voluven that contain the "Vol" prefix in their proprietary name could appear similar: VoLumen (oral contrast media) and Voltaren (oral, ophthalmic, and topical). There is an increased potential for medication error due to similarity in spelling and pronunciation and handwriting of these products with Voluven. Potential for medication errors increases with similarity in placement of letters in the names. VoLumen (oral) has 6 letters similar with the L capitalized, Voltaren has 5 similar letters and could potentially be confused with written and verbal orders for Voluven.
   • Valtropin and Valium had a similar beginning and ending with Voluven and could potentially be confused with poor handwriting and verbal orders.
   • There are marketed product with the "Flo" prefix included in its proprietary name: Flovent (inhaler), Flovent HFA (inhaler), and Flonase (intranasal) which could be confused with the "Vol" prefix of Voluven due to similarity in spelling and pronunciation with verbal order.
   • Other marketed products whose names may be confused due to similarity in verbal and poor handwritten orders for Voluven are: Ventolin (4 similar letters), Fulvicin (3 similar letters) and Flolan (3 similar letters).
   • Marketed influenza products: Afluria, Fluarix, Flulaval, Fluzone, FluMist and Fluvirin are often ordered as "Flu" which is only one syllable and would have a minimal risk for confusion with Voluven.
   • Also because orders often are written with the established name there is potential for confusion with fluticasone (inhaler), and fluvoxamine (oral) because they contain the "Flu" prefix which could be confused with "Vol" prefix.

Name	Dosage Form	Rx or OTC	Dose & Administration	Indication	Storage	Potential
Voluven 6% hydroxyl-ethyl starch 130/0.4 in 0.9% sodium chloride infusion	Suspension for Injection: 500 mL IV bag	RX	Initial dose of 10 to 20 mL slow IV infusion. The proposed daily dose and rate of infusion will depend on the patient. The adult dose may be up to 50 mL /kg/day.	Treatment and prophylaxis of hypovolemia	Room temperature	N/A
VoLumen ® Low Hounsfield Value (LHV) Barium Sulfate Suspension	Suspension, for Oral Contrast as 0.1 w/v, 0.1%w/w in a 450 ml bottle	RX	7 to 11 capsules daily, or as directed by physician	To be used in oral contrast for MDCT and PET/CT studies	Room temperature	High
Voltaren (diclofenac)	Delayed Release tablets: 75 mg	RX	Osteoarthritis dose:100 to 150mg/day in divided doses; RA dose: 150 to 200 mg/day in divided doses Ankylosing Spondylitis: 100 to 125mg/ day	Relief of sign and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis	Room temperature	High
Voltaren XR (diclofenac)	Extended Release tablets: 100 mg	RX	Osteoarthritis dose:100 mg/day; RA dose: 100 mg/day	Relief of sign and symptoms of osteoarthritis and rheumatoid arthritis.	Room temperature	High
Voltaren (diclofenac)	Ophthalmic Solution: 0.1% in 2.5 and 5 ml dropper bottles	RX	Instill 1 to 2 drops into affected eye 4 times a day for up to 14 days.	Postoperative ocular inflammation and ocular pain/photophobia	Room temperature	High
Voltaren (diclofenac)	Topical gel: 1%	RX	Apply gel (2-4 gm) to the affected area 4 times a day.	Osteoarthritis of joints amenable to topical treatment such as knees and hands.		High
Ventolin HFA (albuterol)	Metered Inhaler: Eq 0.09 mg base/inh	RX	For Asthma: 2 puffs every 4 to 6 hours; Exercise Induced B.: 2 puffs 15 to 30 minutes before exercise	Treatment or prevention of bronchospasm in adults & children 4 years of age with reversible obstructive airway disease and prevention of exercise induced bronchospasm in patients 4 years and older	Room temperature	Moderate
Flovent Rotadisk (fluticasone)	Powder for inhalation: 0.05mg/inh, 1mg/inh, and 0.25mg/inh	RX	Orally inhaled dose: Peds 4-11 years: 50-100 mcg twice a day; ≥12 years: 100-500 mcg twice a day	Prophylactic therapy in chronic asthma in patients over 4 years of age	Room temperature	Moderate
Flovent Diskus (fluticasone)	Powder for inhalation: 0.05mg/inh, 1mg/inh, and 0.25mg/inh	RX	Orally inhaled dose: Peds 4-11 years: 88 mcg twice a day; ≥12 years: 88-880 mcg twice a day	Prophylactic therapy in chronic asthma in patients over 4 years of age	Room temperature	Moderate
FloventHFA (fluticasone propionate)	Aerosol: 44 mcg/actuation, 110 mcg/actuation, 220 mcg/actuation in canister.	RX	Orally inhaled dose: Peds 4-11 years: 88 mcg twice a day; ≥12 years: 88-880 mcg twice a day	Prophylactic therapy in chronic asthma in patients over 4 years of age	Room temperature	Moderate
Valtropin (somatropin recombinant DNA origin)	Lypholized Powder for Injection: 5 mg/vial	RX	Subcutaneous injection Preferably in the thighs. Peds with GHD:0.17-0.03 mg/kg/day; Peds with Turner syndrome: 0.053 mg/kg/day; Adults: 0.005 to 0.010mg/kg/day (maximum 0.66 mg/day)	Treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone; or growth failure associated with Turner syndrome in patients with open epiphyses. In adults with growth hormone deficiency as a result of hypothalamic disease, surgery, radiation therapy or trauma or deficiency of growth hormone during childhood.	Refrigerate	Moderate
Fulvicin U/F (griseofulvin, microcrystalline)	Oral tablet: 250 mg, and 500 mg	RX	Adults & teenagers: fungus infections of feet and nails: 250 to 375 mg every 12 hours; infections of scalp, skin and groin: 250 to 375mg once a day; Infants up to 2 yrs: MD determines dose Children over 2 yrs: 2.75 to 3.65 mg/kg every 12 hrs,	Antifungal	Room temperature	Moderate
Flolan (epoprostenol)	Powder for Injection: 0.5 mg base/vial, and 1.5 mg base/vial	RX	2ng/kg/min IV infusion and increase as tolerated (mean dose 11.2 ng/kg/min)	Long-term IV treat-ment of primary pulmonary hypertension and primary pulmonary hypertension associated with scleroderma	Unopened vials are stored at room temperature, Reconstituted must store in refrigerator	Moderate
Flonase (fluticasone)	Intranasal spray: 50 mcg/ Actuation in 16 g amber bottles with nasal adapter	RX	4-11 years: 1 spray in each nostril once a day; ≥12 years: 2 sprays in each nostril once daily	Management of nasal symptoms of seasonal and perennial allergic and nonallergic rhinitis in adults and pediatric patients 4 years of age and older	Room temperature	Moderate
Established name of fluvoxamine	Oral tablets: 25mg, 50 mg, and 100 mg	RX	Children 8-17 years of age: Initiate dose as 25 mg at bedtime and increase if needed up to 100 mg twice a day; Adults: initiate with 50 mg at bedtime and increase up to 150 mg twice a day	Obsessive compulsive disorder (OCD)	Room temperature	Moderate
Valium (diazepam)	Oral tablets: 2 mg, 5 mg, and 10 mg	RX	Child doses:1 to 2.5 mg 3 or 4 times a day Adult doses: Anxiety: 2 to 10 mg 2 to 4 times a day Acute alcohol withdrawal:5-10 mg 3 or 4 times a day Muscle relaxant: 2 to 10 mg 3 to 4 times a day Anticonvulsant: 2 to 10 mg 2 to 4 times a day Geriatrics 2 to 2.5 mg 1 to 2 times a day.	Anxiety disorders, acute alcohol withdrawal, skeletal muscle relaxant, anticonvulsant	Room temperature	Moderate

The following risk factors should also be considered when evaluating the degree to which Voluven may be of concern for medication errors.

Strength/ Dose/Dosage Form/Route of Administration:
Two different products with similar or identical strengths and with proprietary names that sound or look alike could be more easily confused than two products with very different strengths. The risk of confusion increases substantially if two products with similar proprietary names have identical strengths and dosing intervals.

The risk of a medication error is increased when products with similar proprietary names are dosed or prescribed in an identical manner (i.e., once a day). In addition, there is evidence that medication errors can occur even between different dosage forms and routes of administration (capsule vs. injection) and between products with similar proprietary names.

Voluven is supplied as a suspension in 500 mL plastic IV bags. The dose will be individualized and given intravenously by a trained healthcare provider. It will be given over as many days as medically needed.

VoLumen® Low Hounsfield Value (LHV) Barium Sulfate Suspension, 0.1 w/v, 0.1%w/w, is supplied in a 450 ml bottle and administered orally within 6 hours of the diagnostic procedure. Handwritten or verbal orders for Voluven and VoLumen could lead to some confusion with only one letter difference in the name. However, most orders are written using the generic name "barium sulfate", the patient needs dietary restrictions prior to giving the oral barium, and is used for MDCT and PET/CT procedures. Therefore, the likelihood of confusion with the IV Voluven would be lessened.

Unlike Voluven, Valtropin and Flolan, are injectable products that are supplied as powders in small volumes. Voltaren is supplied as oral tablets, ophthalmic solution, and topical gel. Ventolin and Flovent are inhalational products. Flonase is an intranasal spray. While Fulvicin, Fluvoxamine and Valium are oral tablets. None of the listed products are dosed similar to Voluven. However, the potential for confusion due to dosage form and route of administration dosing interval could occur.

Indications and/or Pharmacological-Therapeutic Categories:
The proposed indication for Voluven is for treatment and prophylaxis of hypovolemia. Other products in the table will be not used for hypovolemia.

VoLumen is a neutral oral contrast for MDCT and PET/CT studies. It works with IV contrast to help achieve bowel distension and lumen-to-wall differentiation for visualization. It is administered within 6 hours of the diagnostic procedure which may limit its potential for confusion with Voluven.

Voltaren is a nonsteroidal anti-inflammatory agent used in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and ocular pain or photophobia. It could be used in the same hospital patient setting as Voluven, however because of the difference in dosage forms and a patient needing IV volume replacement the likelihood for a confusion between these products would be lessened.

Different indications will not decrease the risk of confusion since the intended use or indication is not routinely written on a prescription for medication order. Therefore, the possibility of a medication error still exists between the products listed in the table and Voluven if a verbal or written order is received.

Storage Location:
The use of a different storage location (i.e., refrigerator vs. room temperature, oral dosage form location vs. intravenous dosage form location) for two different products with similar names does not significantly decrease the risk of wrong product selection by the health care professional. Therefore, the use of different storage locations for drugs with names that look or sound alike may not mitigate the potential risk of medication errors.

Voluven, Voltaren, Ventolin, Flovent, Fulvicin, Flolan, Flonase, Fluvoxamine, and Valium will be stored at room temperature. VoLumen is also stored at room temperature in pharmacies and areas that supply contrast media. Valtropin will be stored in the refrigerator.

Marketing Status:
Two products with similar proprietary names that are in the same marketing arena (e.g., prescription drug products) could more easily be confused than two products with similar names in different markets (one Rx and the other OTC). Therefore the potential for confusion of these products with Voluven due to marketing status exists.

Packaging and Labeling:
When the container labels, carton labeling, and/ or packaging is similar for two different drug products with similar proprietary names, the risk for confusion with similar proprietary names is increased. The packaging/labeling of the some of marketed products was not available; therefore, the risk of confusion with Voluven due to packaging/labeling could not be evaluated.

Recommendations for proposed names:
APLB recommends that the proposed proprietary name Voluven be found acceptable with concerns. There appears to be a minimal risk for medications errors with the proprietary names for other marketed products, such as, VoLumen and Voltaren, taking into account similarity in spelling, therapeutic class, indication, pronunciation, handwriting, storage, dosage form, route of administration, and marketing status.

If OBRR accepts our recommendation that the proposed proprietary name Voluven be found acceptable with concerns, please include the following text in your letter to the manufacturer:

We have considered your proposed proprietary name Voluven in consultation with CBER's Advertising and Promotional Labeling Branch (APLB) and conclude that under 21 CFR Part 201 the proposed proprietary name is acceptable with concerns at this time.

You should request another proprietary name review of Voluven closer to the time of approval since a significant amount of time may pass between now and licensure of the product and to ensure that FDA has not approved a product with a conflicting proprietary name in the interim.

If you have any questions regarding this review please contact Nancy Chamberlin, at 301-827-3028.

*The following references were used:

1. http: //www.thomsonhc.com/pdrel/librarian (Electronic Physicians' Desk Reference 2007)
2. http://www.factsandcomparisons.com (Drug Facts and Comparisons)
3. http:// www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (CDER approved drug products through October 31, 2007)
4. http://www.fda.gov/cder/ob (Electronic Orange Book through October 17, 2007)
5. http://www.rxlist.com (RxList)
6. http://www.fda.gov/cber/products/htm (CBER New BLA, 510 (k) Devices, NDA and PMA approvals lists through October 31, 2007)
7. http://www.ama-assn.org/ama/pub (American Medical Association Website-Newly Approved USAN stems through October 5, 2007
8. http: //www.acronymfinder.com
9. APhA Handbook of Nonprescription Drugs, 13th Edition, ©2002
10. 2007 American Drug Index