[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]
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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(Betamethasone Sodium Phosphate) Injection Were Not Withdrawn From Sale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.
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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(betamethasone sodium phosphate) injection--were not withdrawn from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