[Federal Register Volume 68, Number 112 (Wednesday, June 11, 2003)]
[Notices]
[Pages 34980-34981]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-14680]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. 02P-0391 and 02P-0404]


Determination That Brimonidine Tartrate Ophthalmic Solution 0.2% 
Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) has determined that 
Alphagan 0.2% (brimonidine tartrate ophthalmic solution) was not 
withdrawn from sale for reasons of safety or effectiveness. This 
determination will allow FDA to approve abbreviated new drug 
applications (ANDAs) for brimonidine tartrate ophthalmic solution 0.2%.

FOR FURTHER INFORMATION CONTACT: Aileen H. Ciampa, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

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 
sponsors 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). Sponsors of ANDAs 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 (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 Under FDA regulations, drugs are withdrawn from the list if the 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

[[Page 34981]]

withdrawn from sale for reasons of safety or effectiveness (21 CFR 
314.162).
    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. FDA may not approve an ANDA that does not refer to a 
listed drug.
    Alphagan 0.2% (brimonidine tartrate ophthalmic solution) is the 
subject of NDA 20-613, held by Allergan, Inc. (Allergan). Alphagan 0.2% 
is administered as an eye drop to lower intraocular pressure in 
patients with open-angle glaucoma or ocular hypertension. FDA approved 
NDA 20-613 on September 6, 1996. In a letter dated August 20, 2002, 
Allergan informed FDA that it was withdrawing Alphagan 0.2% from the 
market. In a letter dated September 6, 2002, Allergan clarified that it 
was not requesting that approval be withdrawn for NDA 20-613, nor was 
Alphagan 0.2% being recalled from the market. Instead, Allergan 
explained that it was in the process of discontinuing distribution of 
Alphagan 0.2%. Following receipt of Allergan's letters, the agency 
moved Alphagan 0.2% from the ``Prescription Drug Product List'' section 
to the ``Discontinued Drug Product List'' section of the Orange Book.
    In citizen petitions submitted under 21 CFR 10.30 and dated August 
27, 2002 (Docket No. 02P-0404/CP1), and August 30, 2002 (Docket No. 
02P-0391/CP1), respectively, Alcon, Inc. (Alcon), and IVAX 
Pharmaceuticals, Inc. (IVAX), requested that the agency determine 
whether brimonidine tartrate ophthalmic solution 0.2% was withdrawn 
from sale for reasons of safety or effectiveness. On October 28, 2002, 
Allergan submitted a citizen petition (Docket No. 02P-0469/CP1) 
opposing the granting of Alcon's and IVAX's petitions. Comments were 
submitted in response to Allergan's petition on November 13, 2002, and 
December 5, 2002, by Alcon and Bausch & Lomb, Inc. (Bausch & Lomb), 
respectively. Allergan responded to the comments on January 23, 2003. 
Bausch & Lomb submitted additional comments on February 10, 2003, and 
Allergan responded on March 18, 2003.
    FDA has considered the information contained in the citizen 
petitions, comments, and agency records and has determined that 
Alphagan 0.2% was not withdrawn from sale for reasons of safety or 
effectiveness. There are several grounds for FDA's finding. First, 
Alphagan 0.2% has a safety and effectiveness profile that is comparable 
to that of Alphagan P (brimonidine tartrate ophthalmic solution 0.15%), 
the subject of NDA 21-262 approved March 16, 2001, for the same 
indication as Alphagan 0.2%. Approval of Alphagan P was based, in part, 
on references to the safety and efficacy of Alphagan 0.2% and the 
products' comparability as demonstrated in head-to-head studies. 
Second, FDA has independently evaluated relevant literature and data 
for possible postmarketing adverse event reports regarding brimonidine 
tartrate ophthalmic solutions, but has found no information that would 
indicate that Alphagan 0.2% was withdrawn for reasons of safety or 
effectiveness.
    After considering the information contained in the citizen 
petitions, comments, and agency records, FDA determines that, for the 
reasons outlined above, brimonidine tartrate ophthalmic solution 0.2% 
approved under NDA 20-613 was not withdrawn from sale for reasons of 
safety or effectiveness. Accordingly, the agency will continue to list 
Alphagan 0.2% (brimonidine tartrate ophthalmic solution) in the 
``Discontinued Drug Product List'' section of the Orange Book. The 
``Discontinued Drug Product List'' delineates, among other items, drug 
products that have been discontinued from marketing for reasons other 
than safety or effectiveness. ANDAs that refer to Alphagan 0.2% 
(brimonidine tartrate ophthalmic solution) may be approved by the 
agency.

    Dated: June 4, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-14680 Filed 6-10-03; 8:45 am]
BILLING CODE 4160-01-S