82_FR_5591 82 FR 5580 - Determination That SYMMETREL (Amantadine Hydrochloride), Syrup, 50 Milligrams/5 Milliliters, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness

82 FR 5580 - Determination That SYMMETREL (Amantadine Hydrochloride), Syrup, 50 Milligrams/5 Milliliters, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 11 (January 18, 2017)

Page Range5580-5581
FR Document2017-01064

The Food and Drug Administration (FDA or Agency) has determined that SYMMETREL (amantadine hydrochloride), Syrup, 50 milligrams/5 milliliters (50 mg/5 mL), was not withdrawn from sale for reasons of safety or effectiveness.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 SYMMETREL, and it will allow FDA to continue to approve ANDAs that reference SYMMETREL if all other legal and regulatory requirements are met.

Federal Register, Volume 82 Issue 11 (Wednesday, January 18, 2017) 
[Federal Register Volume 82, Number 11 (Wednesday, January 18, 2017)]
[Notices]
[Pages 5580-5581]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-01064]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-P-2469]


Determination That SYMMETREL (Amantadine Hydrochloride), Syrup, 
50 Milligrams/5 Milliliters, Was Not Withdrawn From Sale for Reasons of 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 or Agency) has 
determined that SYMMETREL (amantadine hydrochloride), Syrup, 50 
milligrams/5 milliliters (50 mg/5 mL), was not withdrawn from sale for 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 SYMMETREL, and it will allow FDA to 
continue to approve ANDAs that reference SYMMETREL if all other legal 
and regulatory requirements are met.

[[Page 5581]]


FOR FURTHER INFORMATION CONTACT: Stefanie S. Kraus, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6215, Silver Spring, MD 20993-0002, 301-
796-9585.

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 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 (Sec.  314.161 (21 CFR 314.161)). FDA may not approve an ANDA that 
does not refer to a listed drug.
    SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL, is the 
subject of NDAs 016023 and 017118, held by Endo Pharmaceuticals, and 
initially approved on February 14, 1968, and July 20, 1976, 
respectively. SYMMETREL is indicated for the prophylaxis and treatment 
of signs and symptoms of infection caused by various strains of 
influenza A virus. SYMMETREL is also indicated for the treatment of 
parkinsonism and drug-induced extrapyramidal reactions.
    In a letter dated March 19, 2009, Endo Pharmaceuticals notified FDA 
that SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL, was being 
discontinued and requested withdrawal of NDA016023 for that product. 
FDA moved the drug product to the ``Discontinued Drug Product List'' 
section of the Orange Book and announced in the Federal Register of 
July 21, 2010 (75 FR 42455), that FDA was withdrawing approval of NDA 
016023, effective August 20, 2010.
    Hyman, Phelps & McNamara submitted a citizen petition dated August 
3, 2016 (Docket No. FDA-2016-P-2469), under 21 CFR 10.30, requesting 
that the Agency determine whether SYMMETREL (amantadine hydrochloride), 
Syrup, 50 mg/5 mL, was withdrawn from sale for reasons of safety or 
effectiveness.
    After considering the citizen petition and reviewing Agency records 
and based on the information we have at this time, FDA has determined 
under Sec.  314.161 that SYMMETREL (amantadine hydrochloride), Syrup, 
50 mg/5 mL, was not withdrawn for reasons of safety or effectiveness. 
The petitioner has identified no data or other information suggesting 
that this drug product was withdrawn for reasons of safety or 
effectiveness. We have carefully reviewed our files for records 
concerning the withdrawal of SYMMETREL (amantadine hydrochloride), 
Syrup, 50 mg/5 mL, from sale. We have also independently evaluated 
relevant literature and data for possible postmarketing adverse events. 
We have reviewed the available evidence and determined that this drug 
product was not withdrawn from sale for reasons of safety or 
effectiveness.\1\
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    \1\ Due to high levels of resistance to currently circulating 
Influenza A viruses, the Centers for Disease Control and Prevention 
currently recommends against using amantadine to treat Influenza A. 
Given the potential for viral reassortment, however, amantadine may 
be effective against future Influenza A viruses. Consistent with 
this, the current label for SYMMETREL (amantadine hydrochloride), 
Syrup, 50 mg/5 mL, was revised to caution prescribers to consider 
susceptibility and clinical benefit when deciding whether to use 
amantadine to treat Influenza A.
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    Accordingly, the Agency will continue to list SYMMETREL (amantadine 
hydrochloride), Syrup, 50 mg/5 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 SYMMETREL. Additional ANDAs that refer to 
SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL, may 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: January 12, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-01064 Filed 1-17-17; 8:45 am]
 BILLING CODE 4164-01-P

5580 Federal Register / Vol. 82, No. 11 / Wednesday, January 18, 2017 / Notices abbreviated licensure pathway in The draft guidance, when finalized, will III. Paperwork Reduction Act of 1995 section 351(k) for biological products represent the current thinking of FDA This draft guidance refers to shown to be biosimilar to or on topics sponsors should consider previously approved collections of interchangeable with an FDA-licensed when seeking to demonstrate that a information found in FDA regulations. biological reference product (see proposed therapeutic protein product is These collections of information are sections 7001 through 7003 of the interchangeable with a reference subject to review by the Office of Patient Protection and Affordable Care product. It does not establish any rights Management and Budget (OMB) under Act Of 2010 (Affordable Care Act) (Pub. for any person and is not binding on the Paperwork Reduction Act of 1995 L. 111–148)). FDA or the public. (44 U.S.C. 3501–3520). The collections Section 351(k) of the PHS Act sets II. Topics for Comment of information under 21 CFR part 312 forth the requirements for an application for a proposed biosimilar have been approved under OMB control product and an application or a In addition to comment on the draft number 0910–0014; the collections of supplement for a proposed guidance, we also invite general information under 21 CFR part 601 have interchangeable product. Specifically, comments on interchangeability, been approved under OMB control section 351(k)(4) provides that upon including comments on regulation of an number 0910–0338; and the collections review of an application submitted interchangeable product over its of information under section 351(k) of under section 351(k), or any supplement lifecycle, as well as comments on the the PHS Act have been approved under to such an application, FDA will following topics: OMB control number 0910–0719. determine the biological product to be 1. Since the mid-1990s, FDA has IV. Electronic Access interchangeable with the reference approved manufacturing changes for product if FDA determines that the Persons with access to the Internet biological products based on data from may obtain the draft guidance at http:// information submitted in the comparability assessments comparing application (or supplement) is sufficient www.fda.gov/Drugs/Guidance the pre-change and post-change product ComplianceRegulatoryInformation/ to show that the biological product is using comparative analytical, and, when biosimilar to the reference product and Guidances/default.htm, http:// necessary, animal and/or clinical (e.g., www.fda.gov/BiologicsBloodVaccines/ can be expected to produce the same pharmacokinetic, immunogenicity) clinical result as the reference product GuidanceComplianceRegulatory studies. A demonstration of Information/Guidances/default.htm, or in any given patient; and for a biological comparability between pre- and post- product that is administered more than https://www.regulations.gov. change product supports a once to an individual, the risk in terms Dated: January 12, 2017. determination that the safety and of safety or diminished efficacy of Leslie Kux, efficacy profile remains the same for the alternating or switching between use of Associate Commissioner for Policy. product. With respect to the biological product and the reference [FR Doc. 2017–01042 Filed 1–17–17; 8:45 am] interchangeable products, are there product is not greater than the risk of BILLING CODE 4164–01–P using the reference product without considerations in addition to such alternation or switch. Section comparability assessments that FDA 351(i) of the PHS Act states that the should consider in regulating post- DEPARTMENT OF HEALTH AND term interchangeable or approval manufacturing changes of HUMAN SERVICES interchangeability, in reference to a interchangeable products? Your biological product that is shown to meet comments should include the scientific Food and Drug Administration the standards described in subsection rationale and justification for your 351(k)(4), means that the biological recommendations, as well as [Docket No. FDA–2016–P–2469] product may be substituted for the recommendations for processes and reference product without the systems (including key logistics) to Determination That SYMMETREL intervention of the health care provider implement your recommendations. (Amantadine Hydrochloride), Syrup, 50 who prescribed the reference product. 2. As explained in the guidance Milligrams/5 Milliliters, Was Not This guidance gives an overview of ‘‘Considerations in Demonstrating Withdrawn From Sale for Reasons of important scientific considerations in Interchangeability With a Reference Safety or Effectiveness demonstrating interchangeability, Product,’’ FDA expects that sponsors including: AGENCY: Food and Drug Administration, seeking an interchangeability HHS. • The data and information needed to determination will submit data and support a demonstration of information to support a showing that ACTION: Notice. interchangeability; the proposed interchangeable product • Considerations for the design and SUMMARY: The Food and Drug can be expected to produce the same Administration (FDA or Agency) has analysis of a switching study or studies clinical result as the reference product determined that SYMMETREL to support a demonstration of in all of the reference product’s licensed (amantadine hydrochloride), Syrup, 50 interchangeability; • Recommendations regarding the use conditions of use. How, if at all, should milligrams/5 milliliters (50 mg/5 mL), of U.S.-licensed reference products in a the Agency consider conditions of use was not withdrawn from sale for reasons switching study or studies; and that are licensed for the reference of safety or effectiveness. This • Considerations for developing product after an interchangeable determination means that FDA will not mstockstill on DSK3G9T082PROD with NOTICES presentations, container closure product has been licensed? Your begin procedures to withdraw approval systems, and delivery device constituent comments should include the scientific of abbreviated new drug applications parts for proposed interchangeable rationale and justification for your (ANDAs) that refer to SYMMETREL, products. recommendations, as well as and it will allow FDA to continue to This draft guidance is being issued recommendations for processes and approve ANDAs that reference consistent with FDA’s good guidance systems (including key logistics) to SYMMETREL if all other legal and practices regulation (21 CFR 10.115). implement your recommendations. regulatory requirements are met. VerDate Sep<11>2014 17:41 Jan 17, 2017 Jkt 241001 PO 00000 Frm 00059 Fmt 4703 Sfmt 4703 E:\FR\FM\18JAN1.SGM 18JAN1

Federal Register / Vol. 82, No. 11 / Wednesday, January 18, 2017 / Notices 5581 FOR FURTHER INFORMATION CONTACT: In a letter dated March 19, 2009, Endo to SYMMETREL. Additional ANDAs Stefanie S. Kraus, Center for Drug Pharmaceuticals notified FDA that that refer to SYMMETREL (amantadine Evaluation and Research, Food and SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL, Drug Administration, 10903 New hydrochloride), Syrup, 50 mg/5 mL, was may be approved by the Agency as long Hampshire Ave., Bldg. 51, Rm. 6215, being discontinued and requested as they meet all other legal and Silver Spring, MD 20993–0002, 301– withdrawal of NDA016023 for that regulatory requirements for the approval 796–9585. product. FDA moved the drug product of ANDAs. If FDA determines that SUPPLEMENTARY INFORMATION: In 1984, to the ‘‘Discontinued Drug Product List’’ labeling for this drug product should be Congress enacted the Drug Price section of the Orange Book and revised to meet current standards, the Competition and Patent Term announced in the Federal Register of Agency will advise ANDA applicants to Restoration Act of 1984 (Pub. L. 98–417) July 21, 2010 (75 FR 42455), that FDA submit such labeling. (the 1984 amendments), which was withdrawing approval of NDA Dated: January 12, 2017. authorized the approval of duplicate 016023, effective August 20, 2010. Leslie Kux, versions of drug products under an Hyman, Phelps & McNamara submitted a citizen petition dated Associate Commissioner for Policy. ANDA procedure. ANDA applicants [FR Doc. 2017–01064 Filed 1–17–17; 8:45 am] must, with certain exceptions, show that August 3, 2016 (Docket No. FDA–2016– the drug for which they are seeking P–2469), under 21 CFR 10.30, BILLING CODE 4164–01–P approval contains the same active requesting that the Agency determine ingredient in the same strength and whether SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL, was DEPARTMENT OF HEALTH AND dosage form as the ‘‘listed drug,’’ which HUMAN SERVICES is a version of the drug that was withdrawn from sale for reasons of previously approved. ANDA applicants safety or effectiveness. After considering the citizen petition Food and Drug Administration do not have to repeat the extensive and reviewing Agency records and [Docket No. FDA–2010–D–0026] clinical testing otherwise necessary to based on the information we have at this gain approval of a new drug application Assessment of Abuse Potential of time, FDA has determined under (NDA). Drugs; Guidance for Industry; § 314.161 that SYMMETREL The 1984 amendments include what Availability (amantadine hydrochloride), Syrup, 50 is now section 505(j)(7) of the Federal mg/5 mL, was not withdrawn for AGENCY: Food and Drug Administration, Food, Drug, and Cosmetic Act (21 U.S.C. reasons of safety or effectiveness. The HHS. 355(j)(7)), which requires FDA to petitioner has identified no data or other publish a list of all approved drugs. ACTION: Notice of availability. information suggesting that this drug FDA publishes this list as part of the product was withdrawn for reasons of SUMMARY: The Food and Drug ‘‘Approved Drug Products With safety or effectiveness. We have Administration (FDA or Agency) is Therapeutic Equivalence Evaluations,’’ carefully reviewed our files for records announcing the availability of a which is known generally as the concerning the withdrawal of guidance for industry entitled ‘‘Orange Book.’’ Under FDA regulations, SYMMETREL (amantadine ‘‘Assessment of Abuse Potential of drugs are removed from the list if the hydrochloride), Syrup, 50 mg/5 mL, Drugs.’’ This guidance is intended to Agency withdraws or suspends from sale. We have also independently assist sponsors of investigational new approval of the drug’s NDA or ANDA evaluated relevant literature and data drugs and applicants for approval of a for reasons of safety or effectiveness or for possible postmarketing adverse new drug in evaluating whether their if FDA determines that the listed drug events. We have reviewed the available new drug product has abuse potential. was withdrawn from sale for reasons of evidence and determined that this drug Specifically, this guidance provides safety or effectiveness (21 CFR 314.162). product was not withdrawn from sale recommendations for assessing the A person may petition the Agency to for reasons of safety or effectiveness.1 abuse potential of central nervous determine, or the Agency may Accordingly, the Agency will system (CNS)-active new drugs. Drug determine on its own initiative, whether continue to list SYMMETREL products with abuse potential generally a listed drug was withdrawn from sale (amantadine hydrochloride), Syrup, 50 contain drug substances that are active for reasons of safety or effectiveness. mg/5 mL, in the ‘‘Discontinued Drug within the CNS and produce This determination may be made at any Product List’’ section of the Orange psychoactive effects such as euphoria time after the drug has been withdrawn Book. The ‘‘Discontinued Drug Product and hallucinations. Thus, if a drug from sale, but must be made prior to List’’ delineates, among other items, substance is CNS-active, the new drug approving an ANDA that refers to the drug products that have been product containing that drug substance listed drug (§ 314.161 (21 CFR 314.161)). discontinued from marketing for reasons will likely need to undergo a thorough FDA may not approve an ANDA that other than safety or effectiveness. FDA assessment of its abuse potential and does not refer to a listed drug. will not begin procedures to withdraw may be subject to control under the SYMMETREL (amantadine approval of approved ANDAs that refer Controlled Substances Act (CSA). This hydrochloride), Syrup, 50 mg/5 mL, is the subject of NDAs 016023 and 017118, guidance finalizes the draft guidance of 1 Due to high levels of resistance to currently held by Endo Pharmaceuticals, and the same name issued on January 27, circulating Influenza A viruses, the Centers for initially approved on February 14, 1968, Disease Control and Prevention currently 2010. and July 20, 1976, respectively. recommends against using amantadine to treat DATES: Submit either electronic or mstockstill on DSK3G9T082PROD with NOTICES Influenza A. Given the potential for viral SYMMETREL is indicated for the reassortment, however, amantadine may be written comments on Agency guidances prophylaxis and treatment of signs and effective against future Influenza A viruses. at any time. symptoms of infection caused by Consistent with this, the current label for ADDRESSES: You may submit comments various strains of influenza A virus. SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL, was revised to caution prescribers to as follows: SYMMETREL is also indicated for the consider susceptibility and clinical benefit when treatment of parkinsonism and drug- Electronic Submissions deciding whether to use amantadine to treat induced extrapyramidal reactions. Influenza A. VerDate Sep<11>2014 17:41 Jan 17, 2017 Jkt 241001 PO 00000 Frm 00060 Fmt 4703 Sfmt 4703 E:\FR\FM\18JAN1.SGM 18JAN1


Document Created: 2018-02-01 15:19:40
Document Modified: 2018-02-01 15:19:40
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice.
ContactStefanie S. Kraus, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6215, Silver Spring, MD 20993-0002, 301- 796-9585.
FR Citation82 FR 5580 
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