
[Federal Register: June 12, 2008 (Volume 73, Number 114)]
[Notices]               
[Page 33440-33441]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr12jn08-82]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-0321]

 
Hospira, Inc., et al.; Withdrawal of Approval of One New Drug 
Application and Two Abbreviated New Drug Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval 
of one new drug application (NDA) and two abbreviated new drug 
applications (ANDAs) for edetate disodium injection. The holders of 
these applications have agreed in writing to permit FDA to withdraw 
approval of the applications and have waived their opportunity for a 
hearing.

DATES: Effective June 12, 2008.

FOR FURTHER INFORMATION CONTACT: Florine P. Purdie, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 6366, Silver Spring, MD 20993-0002, 301-
796-3601.

SUPPLEMENTARY INFORMATION: FDA informed the holders of the following 
applications that the agency believes a potential problem associated 
with edetate disodium is sufficiently serious that the following drug 
products should be removed from the market:

------------------------------------------------------------------------
   Application No.              Drug                    Applicant
------------------------------------------------------------------------
NDA 11-355            ENDRATE (edetate          Hospira, Inc., 275 North
                       disodium) Injection       Field Dr.,
                                                Lake Forest, IL 60045-
                                                 5046
------------------------------------------------------------------------
ANDA 40-376           Edetate Disodium          Apotex Inc., 150 Signet
                       Injection                 Dr., Toronto,
                                                Ontario, Canada M9L 1T9
------------------------------------------------------------------------
ANDA 40-437           Edetate Disodium          Bioniche Pharma, 272 E.
                       Injection                 Deerpath Rd.,
                                                suite 304, Lake Forest,
                                                 IL 60045
------------------------------------------------------------------------

    Edetate disodium is indicated for the treatment of hypercalcemia 
and for the control of ventricular arrhythmias associated with 
digitalis toxicity. Hospira, Inc. (Hospira), Apotex Inc. (Apotex), and 
Bioniche Pharma (Bioniche) have agreed in writing to permit FDA to 
withdraw approval of their respective applications (listed in the table 
of this document), and to voluntarily remove their respective products 
from the market, under Sec.  314.150(d) (21 CFR 314.150(d)).
    On January 16, 2008, FDA issued a public health advisory to alert 
patients and healthcare professionals about important safety 
information concerning the drug edetate disodium (see ``FDA Public 
Health Advisory: Edetate Disodium (Marketed as ENDRATE and Generic 
Products),'' available on the Internet at http://www.fda.gov/cder/drug/
infopage/edetate_disodium/default.htm). As noted in the January 16, 
2008, Public Health Advisory, there have been cases where children and 
adults have died when they were mistakenly given edetate disodium 
instead of edetate calcium disodium (calcium disodium versenate) or 
when edetate disodium was used for indications other than those 
approved by FDA. FDA asked Hospira, Apotex, and Bioniche to voluntarily 
remove their products (listed in the table of this document) from the 
market because of safety concerns.
    Hospira's NDA 11-355 for ENDRATE was initially approved in 1959 
solely on the basis of safety. The 1962 amendments to the Federal Food, 
Drug, and Cosmetic Act (the act) required that drugs be shown to be 
effective as well. To accomplish this, FDA initiated the Drug Efficacy 
Study Implementation (DESI) review to evaluate the effectiveness of 
drugs that had been previously approved on safety grounds alone. In its 
DESI review of edetate disodium, FDA concluded that edetate disodium 
was effective for the treatment of hypercalcemia and for the control of 
ventricular arrhythmias associated with

[[Page 33441]]

digitalis toxicity, the two approved indications for the drug (35 FR 
437, January 13, 1970).
    In a letter dated September 17, 2007, FDA informed Hospira that the 
agency was reevaluating the safety and efficacy of ENDRATE (edetate 
disodium) Injection based on reports of fatal medication errors and 
reports of serious adverse reactions associated with this product. In 
its September 17, 2007, letter, FDA asked Hospira for additional 
information related to the safety of ENDRATE (edetate disodium) 
Injection.
    On September 19, 2007, FDA sent letters to Apotex and Bioniche for 
ANDAs 40-376 and 40-437, respectively, requesting the same information 
for generic versions of edetate disodium. In a letter dated October 1, 
2007, Hospira provided the postmarketing safety information FDA 
requested on ENDRATE (edetate disodium). In its October 1, 2007, 
letter, Hospira stated that ``[b]ased on the limited indications for 
ENDRATE (edetate disodium) and the availability of alternate medical 
products that offer a superior risk-benefit profile,'' Hospira 
determined that ``the product is not medically necessary.''
    In a letter dated December 7, 2007, under Sec.  314.150(d), FDA 
asked Hospira to waive its opportunity for a hearing (otherwise 
provided for under part 314 (21 CFR part 314)) to permit FDA to 
withdraw approval of NDA 11-355, and to voluntarily remove ENDRATE 
(edetate disodium) from the market. In a letter dated December 20, 
2007, Hospira concurred with FDA's determination to withdraw approval 
of NDA 11-355, ENDRATE (edetate disodium), under Sec.  314.150(d); 
waived its opportunity for a hearing; and agreed to voluntarily remove 
ENDRATE from the market. Hospira initiated a recall of the product.
    In separate telephone conversations on April 8, 2008, FDA asked 
Apotex and Bioniche, under Sec.  314.150(d), to permit FDA to withdraw 
approval of ANDAs 40-376 and 40-437, respectively, for generic versions 
of edetate disodium, and to waive their opportunity for a hearing. 
Apotex and Bioniche, in letters dated April 9, 2008, and April 17, 
2008, respectively, agreed to withdraw their ANDAs under Sec.  
314.150(d). Both Apotex and Bioniche indicated that alternative drug 
products that offer a superior risk-benefit profile are currently 
available for the approved indications for edetate disodium injection. 
Both Apotex and Bioniche waived their opportunity for a hearing 
(otherwise provided under part 314). In its April 9, 2008, letter, 
Apotex stated it has never marketed ANDA 40-376. In its April 17, 2008, 
letter, Bioniche agreed to voluntarily remove its edetate disodium 
product from the market.
    Therefore, under section 505(e) of the act (21 U.S.C. 355(e)), 
Sec.  314.150(d), and under authority delegated to the Director, Center 
for Drug Evaluation and Research, by the Commissioner of Food and 
Drugs, approval of the applications listed in the table of this 
document, and all amendments and supplements thereto, is withdrawn (see 
DATES). Distribution of these products in interstate commerce without 
an approved application is illegal and subject to regulatory action 
(see sections 505(a) and 301(d) of the act (21 U.S.C. 355(a) and 
331(d)). On the basis of the circumstances described in this document 
that led to the withdrawal of approval of the applications listed in 
the table of this document, the agency will remove these products from 
the list of drug products with effective approvals published in FDA's 
``Approved Drug Products With Therapeutic Equivalence Evaluations,'' 
referred to as the ``Orange Book.''

    Dated: May 15, 2008.
Douglas C. Throckmorton,
Deputy Director, Center for Drug Evaluation and Research.
[FR Doc. E8-13273 Filed 6-11-08; 8:45 am]

BILLING CODE 4160-01-S
