[Federal Register Volume 75, Number 86 (Wednesday, May 5, 2010)]
[Notices]
[Pages 24710-24711]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-10559]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2008-P-0284]
Determination That BREVIBLOC (Esmolol Hydrochloride) Injection,
250 Milligrams/Milliliter, 10-Milliliter Ampule, Was Withdrawn From
Sale for Reasons of Safety or Effectiveness
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) has determined that
BREVIBLOC (esmolol hydrochloride (HCl)) Injection, 250 milligrams (mg)/
milliliter (mL), 10-mL ampule, was withdrawn from sale for reasons of
safety or effectiveness. This determination means the agency will not
accept or approve abbreviated new drug applications (ANDAs) for esmolol
HCl injection, 250 mg/mL, 10-mL ampule.
FOR FURTHER INFORMATION CONTACT: Olivia A. Pritzlaff, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 6308, Silver Spring, MD 20993-0002, 301-
796-3601.
SUPPLEMENTARY INFORMATION: In 1984, Congress enacted the Drug Price
Competition and Patent Term Restoration Act of 1984 (Public Law 98-417)
(the 1984 amendments), which authorized the approval of duplicate
versions of drug products approved under an ANDA procedure. ANDA
applicants must, with certain exceptions, show that the drug for which
they are seeking approval contains the same active ingredient in the
same strength and dosage form as the ``listed drug,'' which is a
version of the drug that was previously approved under a new drug
application (NDA). ANDA applicants do not have to repeat the extensive
clinical testing otherwise necessary to gain approval of an NDA. The
only clinical data required in an ANDA are data to show that the drug
that is the subject of the ANDA is bioequivalent to the listed drug.
The 1984 amendments include what is now section 505(j)(7) of the
Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355(j)(7)),
which requires FDA to publish a list of all approved drugs. FDA
publishes this list as part of the ``Approved Drug Products With
Therapeutic Equivalence Evaluations,'' which is generally known as the
``Orange Book.'' Under FDA regulations, drugs are removed from the list
if the agency withdraws or suspends approval of the drug's NDA or ANDA
for reasons of safety or effectiveness, or if FDA determines that the
listed drug was withdrawn from sale for reasons of safety or
effectiveness (section 505(j)(7)(C) of the act; 21 CFR 314.162).
FDA will not approve an ANDA if the listed drug has been withdrawn
from sale for safety or effectiveness reasons (section 505(j)(4)(I) of
the act). Under Sec. 314.161(a)(1) (21 CFR 314.161(a)(1)), the agency
must determine whether a listed drug was withdrawn from sale for
reasons of safety or effectiveness before an ANDA that refers to that
listed drug may be approved. A drug that has been withdrawn from the
market for safety or effectiveness reasons is not a listed drug (21 CFR
314.3(b)). FDA may not approve an ANDA that does not refer to a listed
drug.
BREVIBLOC (esmolol HCl)) Injection is the subject of NDA 19-386,
held by Baxter Healthcare Corp. (Baxter). BREVIBLOC is a
beta1-selective adrenergic receptor-blocking agent with a
short duration of action. BREVIBLOC is approved for the treatment of
supraventricular tachycardia. BREVIBLOC is also indicated for treatment
of intraoperative and postoperative tachycardia and/or hypertension.
Baxter currently markets 4 product presentations of BREVIBLOC
Injection--10-mg/mL and 20-mg/mL ready-to-use vials and 10-mg/mL and
20-mg/mL premixed injection bags. Baxter has discontinued marketing the
following two product presentations of BREVIBLOC (esmolol HCl)
Injection:
In 2003, Baxter discontinued BREVIBLOC (esmolol HCl)
Injection, 10 mg/mL (formulation without sodium chloride), and FDA
determined that this presentation of BREVIBLOC Injection was not
withdrawn from sale for reasons of safety or effectiveness (69 FR
47155, August 4, 2004).
In 2007, Baxter discontinued BREVIBLOC (esmolol HCl)
Injection, 250 mg/mL, 10-mL ampule. In a letter dated June 28, 2007,
Baxter informed the agency that the company had decided to cease
manufacture and distribution of BREVIBLOC (esmolol HCl) Injection, 250
mg/mL, 10-mL ampule, because the product demonstrated a higher risk of
medication errors that may potentially result in serious outcomes.
Baxter observed that serious adverse events were associated with the
following medication errors:
Mixups between the ready-to-use 10-mg/mL vial and the 250-
mg/mL, 10-mL ampule concentrate;
Use of undiluted 250-mg/mL, 10-mL ampule concentrate;
Dilution calculation errors with the 250-mg/mL, 10-mL
ampule concentrate; and
Administration of the wrong drug.
In a Dear Healthcare Professional letter dated August 20, 2007,
Baxter stated that their decision to cease manufacture of BREVIBLOC
(esmolol HCl) Injection, 250 mg/mL, 10-mL ampule, was made after
thorough review of adverse event reports, clinical usage studies, input
from clinicians, and initiatives to reduce medication errors.
In a citizen petition dated March 27, 2008 (Docket No. FDA-2008-P-
0284), submitted under 21 CFR 10.30 and in accordance with 21 CFR
314.122 and 314.161, Bedford Laboratories (Bedford) requested that the
agency determine
[[Page 24711]]
whether BREVIBLOC (esmolol HCl) Injection, 250 mg/mL, 10-mL ampule, was
withdrawn from sale for reasons of safety or effectiveness. Bedford
noted that Baxter has publicly stated that the product was discontinued
due to safety issues surrounding medication errors and asked the agency
to determine the cause of the discontinuation.
We have carefully reviewed our files for records concerning the
withdrawal from sale of BREVIBLOC (esmolol HCl) Injection, 250 mg/mL,
10-mL ampule, including the NDA file for this drug product. We have
also independently evaluated relevant literature and data for possible
postmarketing adverse event reports. FDA's review shows that the
product was withdrawn from sale because of reports of serious adverse
events, including deaths.
Although the application holder has made several labeling revisions
(including a warning sticker on the ampule) and issued Dear Healthcare
Provider letters to reduce the potential for medication errors, there
have been additional reports of medication errors. In addition,
alternative presentations of the product are available that are not
associated with the same potential for medication errors.
After considering the citizen petition (and comments submitted) and
reviewing agency records concerning the drug product, analyses of
adverse event reports, and relevant literature, FDA has determined
under Sec. 314.161 that BREVIBLOC (esmolol HCl) Injection, 250 mg/mL,
10-mL ampule, was withdrawn from sale for reasons of safety or
effectiveness. FDA has reviewed the latest approved labeling for
BREVIBLOC (esmolol HCl) Injection, 250 mg/mL, 10-mL ampule, and has
determined that this labeling is inadequate to reduce medication errors
to an acceptable level. FDA has determined that Human Factors studies
(i.e., Failure Mode and Effects Analysis and usability studies to test
the product in a typical practice setting) are necessary before this
product could be considered for reintroduction to the market.
Therefore, the agency has determined, under Sec. 314.161, that
BREVIBLOC (esmolol HCl) Injection, 250 mg/mL, 10-mL ampule, was
withdrawn from sale for reasons of safety. BREVIBLOC (esmolol HCl)
Injection, 250 mg/mL, 10-mL ampule, will be removed from the list of
drug products published in the Orange Book. FDA will not accept or
approve ANDAs that refer to BREVIBLOC (esmolol HCl) Injection, 250 mg/
mL, 10-mL ampule.
Dated: April 30, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-10559 Filed 5-4-10; 8:45 am]
BILLING CODE 4160-01-S