[Federal Register Volume 71, Number 8 (Thursday, January 12, 2006)]
[Notices]
[Pages 2047-2048]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-178]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. 2004P-0406 and 2004P-0407]


Determination That Celestone Soluspan (Betamethasone Sodium 
Phosphate and Betamethasone Acetate) Injection and Celestone 
(Betamethasone Sodium Phosphate) Injection Were Not Withdrawn From Sale 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) is announcing its 
determination that two drug products--Celestone Soluspan (betamethasone 
sodium phosphate and betamethasone acetate) injection and Celestone 
(betamethasone sodium phosphate) injection--were not withdrawn from 
sale for reasons of safety or effectiveness. This determination will 
allow FDA to approve abbreviated new drug applications (ANDAs) for 
betamethasone sodium phosphate and betamethasone acetate injection and 
betamethasone sodium phosphate injection if all other legal and 
regulatory requirements are met. However, in considering whether to 
file an ANDA for betamethasone sodium phosphate and betamethasone 
acetate injection, future applicants are advised that Celestone 
Soluspan injection may not be commercially available because, under a 
consent decree between FDA and the manufacturer, it is being made 
available in certain instances of medical necessity only. The reasons 
for its unavailability are not safety or effectiveness considerations 
associated with the drug product in general, but specific to the 
manufacturer. An ANDA applicant who is unable to obtain Celestone 
Soluspan injection for bioequivalence testing must contact the Office 
of Generic Drugs for a determination of what is necessary to show 
bioavailability and same therapeutic effect. If the reference listed 
drug (RLD) product becomes commercially available prior to ANDA 
approval, the ANDA applicant will need to show bioequivalence to the 
RLD product.

FOR FURTHER INFORMATION CONTACT: Carol E. Drew, 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 (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 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 withdrawn from sale for reasons of safety or 
effectiveness (21 CFR 314.162). Regulations also provide that the 
agency must make a determination as to 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 (Sec.  
314.161(a)(1) (21 CFR 314.161(a)(1))). FDA may not approve an ANDA that 
does not refer to a listed drug.
    On September 7, 2004, Hikma Farmaceutica (Portugal) LDA submitted 
two citizen petitions (Docket Nos. 2004P-0406/CP1 and 2004P-0407/CP1) 
to FDA under 21 CFR 10.30 requesting that the agency determine whether 
Celestone Soluspan (betamethasone sodium phosphate and betamethasone 
acetate) injection equivalent to 6 milligrams (mg) base/milliliter (mL) 
(NDA 14-602) and Celestone (betamethasone sodium phosphate) injection 
equivalent to 3 mg base/mL (NDA 17-561), both manufactured by Schering-
Plough Corp. (Schering), were withdrawn from sale for reasons of safety 
or effectiveness. Celestone Soluspan injection and Celestone injection 
are corticosteroids used for their anti-inflammatory effects in 
disorders of many organ systems. Schering ceased manufacture of 
Celestone injection in March 2004, and it was moved from the 
prescription drug product list to the ``Discontinued Drug Product 
List'' section of the Orange Book.

[[Page 2048]]

    Schering has not discontinued manufacture of Celestone Soluspan 
injection; however, as a result of a May 2002 consent decree addressing 
manufacturing concerns, Schering's manufacture and distribution of 
Celestone Soluspan injection has been limited to providing the drug for 
certain medically necessary uses under a limited distribution program. 
Celestone Soluspan injection is being distributed as medically 
necessary for the following uses: (1) Neonatal use (fetal lung 
maturation), (2) epidural route for the management of pain due to 
radiculopathy in patients not responsive to systemic drug therapy and 
other adjunctive therapies, and (3) intra-articular and soft tissue 
injections for synovitis of osteoarthritis, acute gouty arthritis, 
nonspecific tenosynovitis, and acute and subacute bursitis. Information 
regarding the current distribution for Celestone Soluspan injection by 
Schering can be found on FDA's Drug Shortage Web site: http://www.fda.gov/cder/drug/shortages/celestone.htm.
    FDA has reviewed its records and, under Sec.  314.161, has 
determined that Celestone Soluspan (betamethasone sodium phosphate and 
betamethasone acetate) injection and Celestone (betamethasone sodium 
phosphate) injection were not withdrawn from sale for reasons of safety 
or effectiveness. Accordingly, the agency will continue to list 
betamethasone sodium phosphate 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 betamethasone sodium phosphate may 
be approved by the agency. ANDAs that refer to betamethasone sodium 
phosphate and betamethasone acetate injection also may be approved by 
the agency; however, FDA recommends that in considering whether to file 
an ANDA for this drug product, future applicants be advised that the 
RLD may not be commercially available because it is being made 
available in certain instances of medical necessity only. An ANDA 
applicant who is unable to obtain Celestone Soluspan injection for 
bioequivalence testing must contact the Office of Generic Drugs for a 
determination of what showing is necessary to satisfy the requirements 
of section 505(j)(2)(A)(iv) of the act. If an ANDA is approved without 
a showing of bioequivalence, the approved product will not be granted 
an AB rating in the Orange Book. Future applicants for betamethasone 
sodium phosphate and betamethasone acetate injection are advised that 
if the RLD product becomes commercially available prior to ANDA 
approval, the ANDA applicant will need to show bioequivalence to the 
RLD product.

    Dated: January 4, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-178 Filed 1-11-06; 8:45 am]
BILLING CODE 4160-01-S