Determination That NOVANTRONE (Mitoxantrone Hydrochloride)
`Injection, Equivalent to 25 Milligrams Base/12.5 Milliliter and
`Equivalent to 30 Milligrams Base/15 Milliliter, Was Not Withdrawn
`From Sale for Reasons of Safety or Effectiveness
`federalregister.gov/documents/2011/04/13/2011-8819/determ nat on-that-novantrone-m toxantrone-hydroch or de- nject on-
`equ va ent-to-25-m grams
`
`Apr 12, 2011
`
`AGENCY:
`Food and Drug Administration, HHS.
`
`ACTION:
`Notice.
`
`SUMMARY:
`The Food and Drug Administration (FDA) has determined that NOVANTRONE (mitoxantrone
`hydrochloride) Injection, equivalent to (EQ) 25 milligrams (mg) base/12.5 milliliters (mL) and EQ
`30 mg base/15 mL, was not withdrawn from sale for reasons of safety or effectiveness. This
`determination means that FDA will not begin procedures to withdraw approval of abbreviated
`new drug applications (ANDAs) that refer to this drug product, and it will allow FDA to continue
`to approve ANDAs that refer to the product as long as they meet relevant legal and regulatory
`requirements.
`
`FOR FURTHER INFORMATION CONTACT:
`Rachel Bressler, Center for Drug Evaluation and Research, Food and Drug Administration, 10903
`New Hampshire Ave., Bldg. 51, rm. 6302, Silver Spring, MD 20993-0002, 301-796-4288.
`
`SUPPLEMENTARY INFORMATION:
`In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984
`(Pub. L. 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of
`drug products 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. ANDA applicants do not have to repeat the extensive clinical testing
`otherwise necessary to gain approval of a new drug application (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.
`
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`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 known generally 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 (21 CFR 314.162).
`A person may petition the Agency to determine, or the Agency may determine on its own
`initiative, whether a listed drug was withdrawn from sale for reasons of safety or effectiveness.
`This determination may be made at any time after the drug has been withdrawn from sale, but
`must be made prior to approving an ANDA that refers to the listed drug (§ 314.161 (21 CFR
`314.161)). FDA may not approve an ANDA that does not refer to a listed drug.
`
`NOVANTRONE (mitoxantrone hydrochloride) Injection, EQ 25 mg base/12.5 mL and EQ 30 mg
`base/15 mL, is the subject of NDA 19-297, held by EMD Serono, and initially approved on
`December 23, 1987. NOVANTRONE is indicated for reducing neurologic disability and/or the
`frequency of clinical relapses in patients with secondary (chronic) progressive, progressive
`relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic
`status is significantly abnormal between relapses). NOVANTRONE (mitoxantrone hydrochloride)
`Injection, EQ 25 mg base/12.5 mL and EQ 30 mg base/15 mL, is currently listed in the
`“Discontinued Drug Product List” section of the Orange Book. There are approved ANDAs for
`NOVANTRONE (mitoxantrone hydrochloride) Injection, EQ 25 mg base/12.5 mL and EQ 30 mg
`base/15 mL; these ANDAs are listed in the Orange Book.
`
`Apotex, Inc., submitted a citizen petition dated September 3, 2008 (Docket No. FDA-2008-P-
`0485), under 21 CFR 10.30, requesting that the Agency determine whether NOVANTRONE
`(mitoxantrone hydrochloride) Injection, 25 mg/12.5 mL and 30 mg/15 mL, was withdrawn from
`sale for reasons of safety or effectiveness.
`
`After considering the citizen petition and reviewing Agency records, FDA has determined under
`§ 314.161 that NOVANTRONE (mitoxantrone hydrochloride) Injection, EQ 25 mg base/12.5 mL
`and EQ 30 mg base/15 mL, was not withdrawn for reasons of safety or effectiveness. The
`petitioner has identified no data or other information suggesting that NOVANTRONE Start
`Printed Page 20686(mitoxantrone hydrochloride) Injection, EQ 25 mg base/12.5 mL and EQ 30
`mg base/15 mL, was withdrawn for reasons of safety or effectiveness. We have carefully
`reviewed our files for records concerning the withdrawal of NOVANTRONE (mitoxantrone
`hydrochloride) Injection, EQ 25 mg base/12.5 mL and EQ 30 mg base/15 mL, from sale. We have
`also independently evaluated relevant literature and data for possible postmarketing adverse
`events. We have found no information that would indicate that this product was withdrawn
`from sale for reasons of safety or effectiveness.
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`Accordingly, the Agency will continue to list NOVANTRONE (mitoxantrone hydrochloride)
`Injection, EQ 25 mg base/12.5 mL and EQ 30 mg base/15 mL, 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. FDA will not begin procedures to withdraw approval of approved ANDAs that
`refer to NOVANTRONE Injection. Additional ANDAs for mitoxantrone hydrochloride injection, EQ
`25 mg base/12.5 mL and EQ 30 mg base/15 mL, may also be approved by the Agency as long as
`they meet all other legal and regulatory requirements for the approval of ANDAs. If FDA
`determines that labeling for this drug product should be revised to meet current standards, the
`Agency will advise ANDA applicants to submit such labeling.
`
`Dated: April 6, 2011.
`
`Leslie Kux,
`
`Acting Assistant Commissioner for Policy.
`
`[FR Doc. 2011-8819 Filed 4-12-11; 8:45 am]
`
`BILLING CODE 4160-01-P
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