NAVINTA LLC FEB loa II: 2 2. February 9, 2011

Transcription

1 February 9, 2011 NAVINTA LLC 2011 FEB loa II: 2 2 Fax: Ms. Michelle Bigesby, Division ofdocuments Management, Food and Drug Administration, Department ofhealth and Human Services; 5630 Fishers Lane; Room 1061; Rockville. MD Subject: Resubmission ofcitizen Petition Document FDA-2011-P-0072 re Venofer Injection Dear Ms. Bigesby; We refer to a communication dated February 9, 2011from Ms. Karen Canova, Regulatory Health Project Manager, Division ofregulatory Policy III, CDERlOffice ofregulatory Policy, FDA. She indicated that we shall withdraw the petition submitted on February 7, 2011 and resubmit the same with inclusion ofa specific sentence in the paragraph pertaining to Certification Requirements. It was also suggested that as there are no changes to the Exhibit A and Exhibit B, there is only need to submit the first six pages ofthe petition along with this cover letter. As suggested, the finn has updated the paragraph pertaining to Certification requirements with inclusion ofthe specific sentence. We are herewith submitting the revised version in duplicate. We thank you for the cooperation. Sincerely, Page I ofl

2 NAVINTA LLC Fax: February 9, 2011 VIA OVERNIGHT DELIVERY Division ofdocuments Management Food and Drug Administration Department of Health and Human Services 5630 Fishers Lane Room 1061 Rockville, MD CITIZEN PETITION The undersigned submits this petition under Section 505 of the Federal Food, Drug, and Cosmetic Act (FDC Act), 21 U.S.C. 355, to request the Commissioner of Food and Drugs to refrain from approving any pending or new applications [submitted under 5050) or 505(b)(2)] of Iron Sucrose Injection drug product, therapeutically equivalent to the Reference Listed Drug product (RLD) Venofer (Iron sucrose injection). A. Action Requested This petition is submitted by Navinta LLC (Navinta) and requests that the Food and Drug Administration (FDA) refrain from granting final approval of any pending or new applications [submitted under 505(j) or 505(b)(2)] of Iron Sucrose Injection drug product, therapeutically equivalent to Venofer and do not exhibit pharmaceutical equivalence to Venofer with respect to the Sodium Content as described within the scope of this petition. Page 1 of

3 NAVINTA LLC Fax: B. Statement of Grounds Iron sucrose Injection (NDA ) was approved by the agency on Nov 06, 2000 and currently it is marketed in the US as a Reference Listed Drug (RLD) under the trade name "Venofer ". V enofer (Iron Sucrose Injection, USP) is a brown, sterile, aqueous, complex ofpolynuclear iron (IH)-hydroxide in sucrose for intravenous use. Iron sucrose injection has a molecular weight of approximately 34,000-60,000 daltons and a proposed structural formula: Where, n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (IH)-hydroxide. Each ml of injection contains 20 mg elemental iron as iron sucrose in water for injection. Venofer is available in 5 ml single dose vials (100 mg elemental iron per 5 ml) and 10 ml single dose vials (200 mg elemental iron per 10 ml). The drug product contains approximately 30% sucrose w/v (300 mglml) and has a ph of The product contains no preservatives. The Osmolarity ofthe injection is 1250 mosmol/l as provided in physician's inert labeling for Venofer (Exhibit A). Page 2 of6

4 NAVINTA LLC Fax: Additionally, United States phannacopoeia (USP) has a monograph for Iron sucrose injection (Exhibit B), which describes that Iron sucrose injection is a sterile, colloidal solution of ferric hydroxide in complex with sucrose in water for injection. It contains not less than 95.0 percent and not more than percent of the labeled amount ofiron. Sodium hydroxide may be added to adjust the ph. It contains no antimicrobial agent, chelating agent, dextran, gluconate, or other added substances.. Elemental Components in Venofer : As described in the molecular formula of Iron sucrose complex printed in the Venofer Label, one can infer that Iron sucrose molecule contains Ferric Iron as polynuclear Iron(lII) hydroxide, Sodium and Sucrose. USP monograph has defined specific tests for the control on content of Iron and content of Sucrose in the drug product, whereas a specific control on the content of sodium was not provided, even though sodium has been described as part of the Iron sucrose molecule (Ref: Venofer Label). As stated in the USP monograph, sodium hydroxide may be added to adjust the ph. This process ofadding sodium hydroxide would introduce additional sodium level into the drug product. Alkalinity Test: USP monograph for Iron sucrose injection has a test for alkalinity, specifying that each ml of Iron sucrose injection should consume not less than 0.5 ml and not more than 0.8 ml of O.IN Hydrochloric acid to bring down the ph to 7.4. Assuming the USP monograph test "Alkalinity" is 1499 Lower Ferry Rd., Ewing. NJ Page 3 of6

5 Phone: NAVINTA LLC Fax: intended to control the amount of sodium present in the Iron sucrose injection, the amount of sodium equivalent to 0.5 ml and 0.8 ml of 0.1 Hydrochloric acid would be correspondingly 1.15 mg/ml and 1.84 mg/ml of injection. Sodium Content: In order to verify the sodium content present in Venofer, three lots were tested for sodium content by ICPMS system using a validated analytical method. The sodium results obtained with three lots ofvenofer are provided in the Table 1. Table 1: Observed Sodium Content in Venofer (Iron Sucrose Injection) Venofer Lot No. Exp. Date Content of Sodium, mglml! i 9500 July August August As evident from the sodium content data reported in Table 1, the values for sodium content are significantly higher than the sodium equivalent to the USP alkalinity test specification. This proves that significant amount of sodium is present in the drug product which did not contribute to the test for alkalinity, meaning this could be the sodium bound to the molecule and hence not neutralized during the titration against 0.1 hydrochloric acid as given in the test for alkalinity described in USP monograph. Page 4 of6

6 NAVINTA LLC Fax: Therefore, it is essential to have a control on the total sodium content in the Iron sucrose injection product so as to ensure pharmaceutical equivalence of composition of a 5050) and/or 505(b)(2) application drug product to that ofvenofer. Based on the sodium content data (about 5.7 mg/ml) observed in Venofer, the agency shall refrain from approving any pending or new applications referencing to Venofer ifthe sodium content is not within a proposed range ofbetween 5.1 mg/ml and 6.6 mg/ml ofdrug product. For the scientific reasons stated within the scope of this petition, all pending or new applications [submitted under 5050) or 505(b)(2)] of Iron Sucrose Injection drug product], before being eligible to receive tentative or final approvals, besides meeting the USP monograph specification for Iron sucrose injection, shall be required to submit evidence to show the amount of sodium present in the respective drug product is similar to that found in Venofer at a proposed specification of between 5.1 mg/ml and 6.6 mg/ml of injection. C. Environmental Impact The relief requested by this petition is categorically exempt from the requirement for an environmental assessment under 21 C.F.R and D. Economic Impact Information regarding economic impact will be submitted upon request. Page 50f6

7 NAVINTA LLC Fax: E. Certification I certify that, to my best knowledge and belief: (a) this petition includes all infonnation and views upon which the petition relies; (b) this petition includes representative data and/or infonnation known to the petitioner which are unfavorable to the petition; and (c) I have taken reasonable steps to ensure that any representative data and/or infonnation which are unfavorable to the petition were disclosed to me. I further certify that the infonnation upon which I have based the action requested herein first became known to the party on whose behalf this petition is submitted on or about the following date: June 29, IfI received or expect to receive payments, including cash and other fonns of consideration, to file this infonnation or its contents, I received or expect to receive those payments from the following persons or organizations: None, other than my usual salary and benefits as an employee of Navinta. I verify under penalty of perjury that the foregoing is true and correct as ofthe date ofthe submission ofthis petition. Respectfully submitted, aj Dave, PhD. Vi President, NavintaLLC 1499 Lower Ferry Road Ewing, NJ (609) Lower Ferry Rd., Ewing. NJ Page 6 of6

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