Final Decision on Withdrawal of MAKENA (Hydroxyprogesterone Caproate) and Eight Abbreviated New Drug Applications Following Public Hearing; Availability of Final Decision, 30986-30987 [2023-10264]

Download as PDF 30986 Federal Register / Vol. 88, No. 93 / Monday, May 15, 2023 / Notices ddrumheller on DSK120RN23PROD with NOTICES1 generally provide that a patent may be extended for a period of up to 5 years so long as the patented item (human drug or biologic product, animal drug product, medical device, food additive, or color additive) was subject to regulatory review by FDA before the item was marketed. Under these acts, a product’s regulatory review period forms the basis for determining the amount of extension an applicant may receive. A regulatory review period consists of two periods of time: a testing phase and an approval phase. For human drug products, the testing phase begins when the exemption to permit the clinical investigations of the drug becomes effective and runs until the approval phase begins. The approval phase starts with the initial submission of an application to market the human drug product and continues until FDA grants permission to market the drug product. Although only a portion of a regulatory review period may count toward the actual amount of extension that the Director of USPTO may award (for example, half the testing phase must be subtracted as well as any time that may have occurred before the patent was issued), FDA’s determination of the length of a regulatory review period for a human drug product will include all of the testing phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA has approved for marketing the human drug product, Onpattro (patisiran), indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Subsequent to this approval, the USPTO received patent term restoration applications for Onpattro (U.S. Patent Nos. 8,168,775; 8,741,866; 9,234,196) from Alnylam Pharmaceuticals, Inc., and the USPTO requested FDA’s assistance in determining the patents’ eligibility for patent term restoration. In a letter dated July 14, 2020, FDA advised the USPTO that this human drug product had undergone a regulatory review period and that the approval of Onpattro represented the first permitted commercial marketing or use of the product. Thereafter, the USPTO requested that FDA determine the product’s regulatory review period. II. Determination of Regulatory Review Period FDA has determined that the applicable regulatory review period for Onpattro is 1,901 days. Of this time, 1,658 days occurred during the testing phase of the regulatory review period, while 243 days occurred during the approval phase. These periods of time were derived from the following dates: VerDate Sep<11>2014 19:07 May 12, 2023 Jkt 259001 1. The date an exemption under section 505(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(i)) became effective: May 29, 2013. Alnylam Pharmaceuticals, Inc. claims that June 7, 2013, is the date the investigational new drug application (IND) became effective. However, FDA’s records indicate that the effective date of the IND was May 29, 2013, which was the first date after receipt of the IND that the investigational studies could proceed. 2. The date the application was initially submitted with respect to the human drug product under section 505 of the FD&C Act: December 11, 2017. FDA has verified the applicant’s claim that the new drug application (NDA) for Onpattro (NDA 210922) was initially submitted on December 11, 2017. 3. The date the application was approved: August 10, 2018. FDA has verified the applicant’s claim that NDA 210922 was approved on August 10, 2018. This determination of the regulatory review period establishes the maximum potential length of a patent extension. However, the USPTO applies several statutory limitations in its calculations of the actual period for patent extension. In its applications for patent extension, this applicant seeks 593 days, 887 days or 1,025 days of patent term extension. III. Petitions Anyone with knowledge that any of the dates as published are incorrect may submit either electronic or written comments and, under 21 CFR 60.24, ask for a redetermination (see DATES). Furthermore, as specified in § 60.30 (21 CFR 60.30), any interested person may petition FDA for a determination regarding whether the applicant for extension acted with due diligence during the regulatory review period. To meet its burden, the petition must comply with all the requirements of § 60.30, including but not limited to: must be timely (see DATES), must be filed in accordance with § 10.20, must contain sufficient facts to merit an FDA investigation, and must certify that a true and complete copy of the petition has been served upon the patent applicant. (See H. Rept. 857, part 1, 98th Cong., 2d sess., pp. 41–42, 1984.) Petitions should be in the format specified in 21 CFR 10.30. Submit petitions electronically to https://www.regulations.gov at Docket No. FDA–2013–S–0610. Submit written petitions (two copies are required) to the Dockets Management Staff (HFA–305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. PO 00000 Frm 00044 Fmt 4703 Sfmt 4703 Dated: May 10, 2023. Lauren K. Roth, Associate Commissioner for Policy. [FR Doc. 2023–10317 Filed 5–12–23; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2020–N–2029] Final Decision on Withdrawal of MAKENA (Hydroxyprogesterone Caproate) and Eight Abbreviated New Drug Applications Following Public Hearing; Availability of Final Decision AGENCY: Food and Drug Administration, HHS. ACTION: Notice. The Food and Drug Administration (FDA or Agency) is announcing the availability of the final decision withdrawing approval of MAKENA (hydroxyprogesterone caproate injection, 250 milligrams (mg) per milliliter (mL), once weekly), under the new drug application (NDA) 021945, held by Covis Pharma Group/Covis Pharma GmbH (Covis), and the eight abbreviated new drug applications (ANDAs) from multiple ANDA holders that reference NDA 021945. The Commissioner of Food and Drugs (the Commissioner) and the Chief Scientist jointly issued the decision following an October 2022 public hearing. DATES: Approval of MAKENA and the ANDAs that reference MAKENA is withdrawn as of April 6, 2023. FOR FURTHER INFORMATION CONTACT: Patrick Raulerson, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6260, Silver Spring, MD 20993–0002, 301– 796–3522, Patrick.Raulerson@ fda.hhs.gov. SUMMARY: SUPPLEMENTARY INFORMATION: I. Background On February 3, 2011, FDA’s Center for Drug Evaluation and Research (CDER) approved NDA 021945 for MAKENA (hydroxyprogesterone caproate) Injection to reduce the risk of preterm birth (PTB) in women with a singleton pregnancy who have a history of singleton spontaneous PTB (sPTB). FDA approved MAKENA under the accelerated approval pathway, pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356(c)) and 21 CFR 314.510, based on evidence of the drug’s effect on E:\FR\FM\15MYN1.SGM 15MYN1 30987 Federal Register / Vol. 88, No. 93 / Monday, May 15, 2023 / Notices ddrumheller on DSK120RN23PROD with NOTICES1 an intermediate clinical endpoint that was considered reasonably likely to predict the drug’s clinical benefit. As a condition of MAKENA’s approval, the sponsor was required to complete a postmarketing trial to verify and describe the clinical benefit of MAKENA in reducing neonatal morbidity and mortality from complications of PTB among babies born to women with a singleton pregnancy who had a previous singleton sPTB. This postmarketing confirmatory trial, Trial 003, failed to show that MAKENA reduced the risk of neonatal morbidity and mortality from complications of PTB and failed to show a treatment effect of MAKENA on the intermediate clinical endpoint that was the basis of MAKENA’s approval. On October 5, 2020, CDER issued a proposal to withdraw approval of MAKENA and a notice of opportunity for hearing (NOOH) on two independent grounds using expedited procedures under section 506(c)(3) of the FD&C Act and 21 CFR 314.530(a): (1) the confirmatory trial failed to verify the clinical benefit of the drug and (2) the evidence demonstrates that the drug is not shown to be effective under its conditions of use. CDER’s NOOH and proposal to withdraw approval of MAKENA also provided notice to all holders of approved ANDAs referencing the NDA for MAKENA (NDA 021945) that, if the Agency were to withdraw approval of MAKENA, CDER would withdraw approval of those ANDAs under 21 CFR 314.151(b)(3). MAKENA’s sponsor submitted a hearing request dated October 14, 2020, followed by a submission of data and information in support of the hearing request. The Agency granted the sponsor’s hearing request on August 18, 2021, and on August 17, 2022, published a notice of hearing (87 FR 50626). The hearing was held on October 17, 18, and 19, 2022. The Obstetrics, Reproductive and Urologic Drugs Advisory Committee was present at the hearing to review the issues involved and to provide advice and recommendations to the Commissioner. The presiding officer issued a report, dated January 19, 2023, that summarized the legal and factual background, content of the hearing, and her analysis and recommendations. On April 6, 2023, after considering CDER’s and Covis’ March 6, 2023, post-hearing submissions, the Commissioner and Chief Scientist jointly issued a final decision withdrawing approval of MAKENA and the ANDAs that referenced MAKENA. FDA has withdrawn approvals of the following NDA and eight ANDAs: Application No. Drug Holder/sponsor NDA 021945 .......... Makena (hydroxyprogesterone caproate) Injection, 250 mg per mL ..................... ANDA ANDA ANDA ANDA ANDA ANDA ANDA ANDA Hydroxyprogesterone Hydroxyprogesterone Hydroxyprogesterone Hydroxyprogesterone Hydroxyprogesterone Hydroxyprogesterone Hydroxyprogesterone Hydroxyprogesterone Covis Pharma Group/Covis Pharma GmbH. Sun Pharmaceutical Industries, Ltd. Slayback Pharma LLC. American Regent, Inc. Do. Slayback Pharma LLC. Eugia Pharma Specialities Ltd. Do. Aspen Pharma USA Inc. 208381 210618 210723 210724 210877 211070 211071 211777 ........ ........ ........ ........ ........ ........ ........ ........ Caproate Caproate Caproate Caproate Caproate Caproate Caproate Caproate Withdrawal of approval of the applications listed in the table includes all strengths, dosage forms, amendments, and supplements to these applications, effective April 6, 2023. As discussed in the decision of the Commissioner and Chief Scientist, FDA has withdrawn approval of the MAKENA NDA for reasons of safety or effectiveness, as well as approval of the ANDAs that reference MAKENA. Section 505(j)(7) of the FD&C Act (21 U.S.C. 355(j)(7)) 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,’’ available at https:// www.accessdata.fda.gov/scripts/cder/ ob/index.cfm. 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. Accordingly, the Agency has removed the applications listed in the table from the list of drug products published in VerDate Sep<11>2014 19:07 May 12, 2023 Jkt 259001 Injection Injection Injection Injection Injection Injection Injection Injection USP, USP, USP, USP, USP, USP, USP, USP, 250 250 250 250 250 250 250 250 mg/mL mg/mL mg/mL mg/mL mg/mL mg/mL mg/mL mg/mL .................................. .................................. .................................. .................................. .................................. .................................. .................................. .................................. the Orange Book. FDA will not accept or approve ANDAs that reference MAKENA. II. Electronic Access Persons with access to the internet may obtain the final decision at https:// downloads.regulations.gov/FDA-2020N-2029-0385/attachment_1.pdf. The final decision, a transcript of the hearing, and other documents pertaining to the withdrawal of the NDA for MAKENA (NDA 021945) are available at https://www.regulations.gov under the docket number found in brackets in the heading of this document. Dated: May 8, 2023. Lauren K. Roth, Associate Commissioner for Policy. [FR Doc. 2023–10264 Filed 5–12–23; 8:45 am] BILLING CODE 4164–01–P PO 00000 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA–2020–E–1905 and FDA– 2020–E–1896] Determination of Regulatory Review Period for Purposes of Patent Extension; Tack Endovascular System (6F) AGENCY: Food and Drug Administration, HHS. ACTION: Notice. The Food and Drug Administration (FDA or the Agency) has determined the regulatory review period for Tack Endovascular System (6F) and is publishing this notice of that determination as required by law. FDA has made the determination because of the submission of applications to the Director of the U.S. Patent and Trademark Office (USPTO), Department of Commerce, for the extension of patents which claim that medical device. SUMMARY: Anyone with knowledge that any of the dates as published (see DATES: Frm 00045 Fmt 4703 Sfmt 4703 E:\FR\FM\15MYN1.SGM 15MYN1

Agencies

[Federal Register Volume 88, Number 93 (Monday, May 15, 2023)]
[Notices]
[Pages 30986-30987]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-10264]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-2029]


Final Decision on Withdrawal of MAKENA (Hydroxyprogesterone 
Caproate) and Eight Abbreviated New Drug Applications Following Public 
Hearing; Availability of Final Decision

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of the final decision withdrawing approval of MAKENA 
(hydroxyprogesterone caproate injection, 250 milligrams (mg) per 
milliliter (mL), once weekly), under the new drug application (NDA) 
021945, held by Covis Pharma Group/Covis Pharma GmbH (Covis), and the 
eight abbreviated new drug applications (ANDAs) from multiple ANDA 
holders that reference NDA 021945. The Commissioner of Food and Drugs 
(the Commissioner) and the Chief Scientist jointly issued the decision 
following an October 2022 public hearing.

DATES: Approval of MAKENA and the ANDAs that reference MAKENA is 
withdrawn as of April 6, 2023.

FOR FURTHER INFORMATION CONTACT: Patrick Raulerson, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6260, Silver Spring, MD 20993-0002, 301-
796-3522, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    On February 3, 2011, FDA's Center for Drug Evaluation and Research 
(CDER) approved NDA 021945 for MAKENA (hydroxyprogesterone caproate) 
Injection to reduce the risk of preterm birth (PTB) in women with a 
singleton pregnancy who have a history of singleton spontaneous PTB 
(sPTB). FDA approved MAKENA under the accelerated approval pathway, 
pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act) (21 U.S.C. 356(c)) and 21 CFR 314.510, based on evidence of 
the drug's effect on

[[Page 30987]]

an intermediate clinical endpoint that was considered reasonably likely 
to predict the drug's clinical benefit.
    As a condition of MAKENA's approval, the sponsor was required to 
complete a postmarketing trial to verify and describe the clinical 
benefit of MAKENA in reducing neonatal morbidity and mortality from 
complications of PTB among babies born to women with a singleton 
pregnancy who had a previous singleton sPTB. This postmarketing 
confirmatory trial, Trial 003, failed to show that MAKENA reduced the 
risk of neonatal morbidity and mortality from complications of PTB and 
failed to show a treatment effect of MAKENA on the intermediate 
clinical endpoint that was the basis of MAKENA's approval.
    On October 5, 2020, CDER issued a proposal to withdraw approval of 
MAKENA and a notice of opportunity for hearing (NOOH) on two 
independent grounds using expedited procedures under section 506(c)(3) 
of the FD&C Act and 21 CFR 314.530(a): (1) the confirmatory trial 
failed to verify the clinical benefit of the drug and (2) the evidence 
demonstrates that the drug is not shown to be effective under its 
conditions of use. CDER's NOOH and proposal to withdraw approval of 
MAKENA also provided notice to all holders of approved ANDAs 
referencing the NDA for MAKENA (NDA 021945) that, if the Agency were to 
withdraw approval of MAKENA, CDER would withdraw approval of those 
ANDAs under 21 CFR 314.151(b)(3).
    MAKENA's sponsor submitted a hearing request dated October 14, 
2020, followed by a submission of data and information in support of 
the hearing request. The Agency granted the sponsor's hearing request 
on August 18, 2021, and on August 17, 2022, published a notice of 
hearing (87 FR 50626). The hearing was held on October 17, 18, and 19, 
2022. The Obstetrics, Reproductive and Urologic Drugs Advisory 
Committee was present at the hearing to review the issues involved and 
to provide advice and recommendations to the Commissioner. The 
presiding officer issued a report, dated January 19, 2023, that 
summarized the legal and factual background, content of the hearing, 
and her analysis and recommendations. On April 6, 2023, after 
considering CDER's and Covis' March 6, 2023, post-hearing submissions, 
the Commissioner and Chief Scientist jointly issued a final decision 
withdrawing approval of MAKENA and the ANDAs that referenced MAKENA.
    FDA has withdrawn approvals of the following NDA and eight ANDAs:

------------------------------------------------------------------------
      Application No.                  Drug             Holder/sponsor
------------------------------------------------------------------------
NDA 021945.................  Makena                   Covis Pharma Group/
                              (hydroxyprogesterone     Covis Pharma
                              caproate) Injection,     GmbH.
                              250 mg per mL.
ANDA 208381................  Hydroxyprogesterone      Sun Pharmaceutical
                              Caproate Injection       Industries, Ltd.
                              USP, 250 mg/mL.
ANDA 210618................  Hydroxyprogesterone      Slayback Pharma
                              Caproate Injection       LLC.
                              USP, 250 mg/mL.
ANDA 210723................  Hydroxyprogesterone      American Regent,
                              Caproate Injection       Inc.
                              USP, 250 mg/mL.
ANDA 210724................  Hydroxyprogesterone      Do.
                              Caproate Injection
                              USP, 250 mg/mL.
ANDA 210877................  Hydroxyprogesterone      Slayback Pharma
                              Caproate Injection       LLC.
                              USP, 250 mg/mL.
ANDA 211070................  Hydroxyprogesterone      Eugia Pharma
                              Caproate Injection       Specialities Ltd.
                              USP, 250 mg/mL.
ANDA 211071................  Hydroxyprogesterone      Do.
                              Caproate Injection
                              USP, 250 mg/mL.
ANDA 211777................  Hydroxyprogesterone      Aspen Pharma USA
                              Caproate Injection       Inc.
                              USP, 250 mg/mL.
------------------------------------------------------------------------

    Withdrawal of approval of the applications listed in the table 
includes all strengths, dosage forms, amendments, and supplements to 
these applications, effective April 6, 2023. As discussed in the 
decision of the Commissioner and Chief Scientist, FDA has withdrawn 
approval of the MAKENA NDA for reasons of safety or effectiveness, as 
well as approval of the ANDAs that reference MAKENA.
    Section 505(j)(7) of the FD&C Act (21 U.S.C. 355(j)(7)) 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,'' 
available at https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. 
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. Accordingly, the Agency has removed the applications listed in 
the table from the list of drug products published in the Orange Book. 
FDA will not accept or approve ANDAs that reference MAKENA.

II. Electronic Access

    Persons with access to the internet may obtain the final decision 
at https://downloads.regulations.gov/FDA-2020-N-2029-0385/attachment_1.pdf. The final decision, a transcript of the hearing, and 
other documents pertaining to the withdrawal of the NDA for MAKENA (NDA 
021945) are available at https://www.regulations.gov under the docket 
number found in brackets in the heading of this document.

    Dated: May 8, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-10264 Filed 5-12-23; 8:45 am]
BILLING CODE 4164-01-P

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