Notice2023-10264
Final Decision on Withdrawal of MAKENA (Hydroxyprogesterone Caproate) and Eight Abbreviated New Drug Applications Following Public Hearing; Availability of Final Decision
Primary source
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Published
May 15, 2023
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
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.
Full Text
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<title>Federal Register, Volume 88 Issue 93 (Monday, May 15, 2023)</title>
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[Federal Register Volume 88, Number 93 (Monday, May 15, 2023)]
[Notices]
[Pages 30986-30987]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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.
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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withdrawn as of April 6, 2023.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, <a href="/cdn-cgi/l/email-protection#d787b6a3a5beb4bcf985b6a2bbb2a5a4b8b997b1b3b6f9bfbfa4f9b0b8a1"><span class="__cf_email__" data-cfemail="beeedfcaccd7ddd590ecdfcbd2dbcccdd1d0fed8dadf90d6d6cd90d9d1c8">[email protected]</span></a>.
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:
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Application No. Drug Holder/sponsor
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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.
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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 <a href="https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm">https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm</a>.
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 <a href="https://downloads.regulations.gov/FDA-2020-N-2029-0385/attachment_1.pdf">https://downloads.regulations.gov/FDA-2020-N-2029-0385/attachment_1.pdf</a>. 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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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