(2) Who is a consignor under State law as prescribed by State law
related to security interests in goods; or
    (3) Who holds a security interest arising under State law related
to security interests in goods.
    Secured party of record means the secured party whose name is
indicated as the name of the secured party in the files of the office
or, if the files indicate more than one secured party, the one first
indicated.
    Security interest means an interest in a vessel that secures
payment or performance of an obligation if the interest is created by
contract or otherwise as prescribed by state law related to security
interests in goods.
    Sign means, with present intent to authenticate or adopt a record,
to--
    (1) Make or adopt a tangible symbol; or
    (2) Attach to or logically associate with the record an electronic
symbol, sound, or process.
    State means a State of the United States, the District of Columbia,
American Samoa, Guam, Northern Mariana Islands, Puerto Rico, U.S.
Virgin Islands, and any other territory or possession of the United
States.
    State of principal operation means the State on whose waters a
vessel is or will be used, operated, navigated, or employed more than
on the waters of any other State during a calendar year.
    Title brand means a designation of previous damage, use, or
condition that must be indicated on a certificate of title.
    Titled vessel means a vessel titled by a State.
    Titling authority means a State whose vessel titling system has
been certified by the Commandant under subpart D of this part.
    Transfer of ownership means a voluntary or involuntary conveyance
of an interest in a vessel.
    Vessel means every description of watercraft used or capable of
being used as a means of transportation on water, except--
    (1) A seaplane;
    (2) An amphibious vehicle for which a certificate of title is
issued pursuant to a state's motor vehicle certificate of title act or
a similar statute of another state;
    (3) Watercraft that operate only on a permanently fixed,
manufactured course and the movement of which is restricted to or
guided by means of a mechanical device to which the watercraft is
attached or by which the watercraft is controlled;
    (4) A stationary floating structure that--
    (i) Does not have and is not designed to have a mode of propulsion
of its own;
    (ii) Is dependent for utilities upon a continuous utility hookup to
a source originating on shore; and
    (iii) Has a permanent, continuous hookup to a shore side sewage
system.
    (5) Watercraft owned by the United States, a State, or a foreign
government or a political subdivision of any of them; and
    (6) Watercraft used solely as a lifeboat on another watercraft.
    Vessel Identification System or VIS means a system for collecting
information on vessels and vessel

ownership as required by 46 U.S.C. 12501.
    Vessel number means the alphanumeric designation for a vessel
issued pursuant to 46 U.S.C. 12301.
    Written certificate of title means a certificate of title
consisting of information inscribed on a tangible medium.

0
3. Revise subpart D to read as follows:
Subpart D--State Vessel Titling Systems
Sec.
187.301 Certification for preferred mortgage status--Eligibility
requirements.
187.302 Terms States must define.
187.303 Applicability.
187.304 Titling exclusively in one State.
187.305 Law governing vessel covered by certificate of title.
187.306 Certificate of title required.
187.307 Application for certificate of title.
187.308 Creation and cancellation of certificate of title.
187.309 Content of certificate of title.
187.310 Title brand.
187.311 Maintenance of and access to files.
187.312 Action required on creation of certificate of title.
187.313 Effect of certificate of title.
187.314 Effect of possession of certificate of title; judicial
process.
187.315 Perfection of security interest.
187.316 Termination statement.
187.317 Transfer of ownership.
187.318 Effect of missing or incorrect information.
187.319 Transfer of ownership by secured party's transfer statement.
187.320 Transfer by operation of law.
187.321 Application for transfer of ownership or termination of
security interest without certificate of title.
187.322 Replacement certificate of title.
187.323 Rights of purchaser other than secured party.
187.324 Rights of secured party.
187.325 Duties and operation of office.

Subpart D--State Vessel Titling Systems

Sec.  187.301   Certification for preferred mortgage status--
Eligibility requirements.

    The Commandant, under 46 U.S.C. 31322(d)(1)(A) and Sec.  187.13,
will certify a State whose vessel titling system meets the requirements
of this subpart as eligible to have security interests that are
perfected under its law deemed preferred mortgages under 46 U.S.C.
31322. The State must also comply with the VIS participation
requirements of Sec.  187.11 and subpart C of this part and make vessel
information it collects available to the VIS.

Sec.  187.302   Terms States must define.

    (a) A State must define the terms ``certificate of origin'',
``dealer'', ``documented vessel'', ``issuing authority'',
``manufacturer'', ``owner'', ``person'', ``secured party'', ``security
interest'', ``titling authority'', and ``vessel'' substantially as
defined in 33 CFR 187.7.
    (b) In addition to the definitions in Sec.  187.7, a State must
also define the following terms as prescribed by State law related to
security interests in goods:
    (1) Agreement;
    (2) Buyer in ordinary course of business;
    (3) Conspicuous;
    (4) Consumer goods;
    (5) Debtor;
    (6) Knowledge;
    (7) Lease;
    (8) Lessor;
    (9) Notice;
    (10) Representative;
    (11) Sale;
    (12) Security agreement;
    (13) Seller;
    (14) Send; and
    (15) Value.
    (c) The definitions in Sec.  187.7 and the terms in paragraph (b)
of this section do not apply to any State or Federal law governing
licensing, numbering, or registration if the same term is used in that
law.

Sec.  187.303   Applicability.

    Subject to a savings clause provided under state law, this subpart
applies to any transaction, certificate of title, or record relating to
a vessel, even if the transaction, certificate of title, or record was
entered into or created before the effective date of the State law.

Sec.  187.304   Titling exclusively in one State.

    A State must require that all vessels required to be numbered in
the State under 46 U.S.C. Chapter 123 be titled only in that State, if
that State issues titles to that class of vessels.

Sec.  187.305   Law governing vessels covered by certificate of title.

    (a) The local law of the State under whose certificate of title a
vessel is covered governs all issues relating to the certificate from
the time the vessel becomes covered by the certificate until the vessel
becomes covered by another certificate or becomes a documented vessel,
even if no other relationship exists between the State and the vessel
or its owner.
    (b) A vessel becomes covered by a certificate of title when an
application for the certificate and the applicable fee are delivered to
the office in accordance with this subpart or to the governmental
agency that creates a certificate in another jurisdiction in accordance
with the law of that jurisdiction.

Sec.  187.306   Certificate of title required.

    (a) Except as otherwise provided in paragraphs (b) and (c) of this
section, the owner of a vessel must deliver to the office of the State
in which the vessel is principally used an application for a
certificate of title for the vessel, with the applicable fee, not later
than 20 days after the later of--
    (1) The date of a transfer of ownership; or
    (2) The date the State becomes the State of principal use.
    (b) An application for a certificate of title is not required for--
    (1) A documented vessel;
    (2) A foreign-documented vessel;
    (3) A barge;
    (4) A vessel before delivery if the vessel is under construction or
completed pursuant to contract; or
    (5) A vessel held by a dealer for sale or lease.
    (c) The office may not issue, transfer, or renew a certificate of
number for a vessel issued pursuant to 46 U.S.C. 12301 unless it has
created a certificate of title for the vessel or an application for a
certificate for the vessel and the applicable fee have been delivered
to the office.

Sec.  187.307   Application for certificate of title.

    (a) Except as otherwise provided in Sec. Sec.  187.310, 187.315,
187.319, 187.320, 187.321, and 187.322, only an owner may apply for a
certificate of title.
    (b) An application for a certificate of title must be signed by the
applicant and contain--
    (1) The applicant's name, the street address of the applicant's
principal residence, and, if different, the applicant's mailing
address;
    (2) The name and mailing address of each other owner of the vessel;
    (3) The social security number or taxpayer identification number of
each owner;
    (4) The hull identification number (HIN) for the vessel or, if
none, an application for the issuance of a HIN for the vessel;
    (5) The vessel number for the vessel or, if none issued by the
office, an application for a vessel number;
    (6) A description of the vessel as required by the office, which
must include--
    (i) The official number for the vessel, if any, assigned by the
Coast Guard;
    (ii) The name of the manufacturer, builder, or maker;
    (iii) The model year or the year in which the manufacture or build
of the vessel was completed;
    (iv) The overall length of the vessel;
    (v) The vessel type, as described in 33 CFR 174.19;
    (vi) The hull material, as described in 33 CFR 174.19;
    (vii) The propulsion type, as described in 33 CFR 174.19;

    (viii) The engine drive type, as described in 33 CFR 174.19, if
any; and
    (ix) The fuel type, as described in 33 CFR 174.19, if any;
    (7) An indication of all security interests in the vessel known to
the applicant and the name and mailing address of each secured party;
    (8) A statement that the vessel is not a documented vessel or a
foreign-documented vessel;
    (9) Any title brand known to the applicant and, if known, the
jurisdiction under whose law the title brand was created;
    (10) If the applicant knows that the vessel is hull damaged, a
statement that the vessel is hull damaged;
    (11) If the application is made in connection with a transfer of
ownership, the transferor's name, street address, and, if different,
mailing address, the sales price, if any, and the date of the transfer;
and
    (12) If the vessel was previously registered or titled in another
jurisdiction, a statement identifying each jurisdiction known to the
applicant in which the vessel was registered or titled.
    (c) In addition to the information required by paragraph (b) of
this section, an application for a certificate of title may contain an
electronic communication address of the owner, transferor, or secured
party.
    (d) Except as otherwise provided in Sec. Sec.  187.319, 187.320,
187.321, and 187.322, an application for a certificate of title must be
accompanied by a certificate of title signed by the owner shown on the
certificate which identifies the applicant as the owner of the vessel,
or is accompanied by a record that identifies the applicant as the
owner.
    (e) If there is no certificate of title as discussed in paragraph
(d) of this section, an application for a certificate of title must be
accompanied by--
    (1) If the vessel was a documented vessel, a record issued by the
Coast Guard that shows the vessel is no longer a documented vessel and
identifies the applicant as the owner;
    (2) If the vessel was a foreign-documented vessel, a record issued
by the foreign country which shows the vessel is no longer a foreign-
documented vessel and identifies the applicant as the owner; or
    (3) In all other cases, a certificate of origin, bill of sale, or
other record that to the satisfaction of the office identifies the
applicant as the owner.
    (f) A record submitted in connection with an application is part of
the application and the office must maintain it in its files.
    (g) The office may require an application for a certificate of
title to be accompanied by payment or evidence of payment of all fees
and taxes payable by the applicant under State law if in connection
with the application or the acquisition or use of the vessel.

Sec.  187.308   Creation and cancellation of certificate of title.

    (a) Unless an application for a certificate of title is rejected
under paragraph (c) or (d) of this section, the office must create a
certificate for the vessel in accordance with paragraph (b) of this
section not later than 20 days after delivery to it of an application
that complies with Sec.  187.307.
    (b) If the office creates electronic certificates of title, it must
create an electronic certificate unless in the application the secured
party of record or, if none, the owner of record, requests that the
office create a written certificate.
    (c) Except as otherwise provided in paragraph (d) of this section,
the office may reject an application for a certificate of title only
if--
    (1) The application does not comply with Sec.  187.307;
    (2) The application does not contain documentation sufficient for
the office to determine whether the applicant is entitled to a
certificate;
    (3) There is a reasonable basis for concluding that the application
is fraudulent or issuance of a certificate would facilitate a
fraudulent or illegal act; or
    (4) The application does not comply with State law.
    (d) The office must reject an application for a certificate of
title for a vessel that is a documented vessel or a foreign-documented
vessel.
    (e) The office may cancel a certificate of title created by it only
if the office--
    (1) Could have rejected the application for the certificate under
paragraph (c) of this section;
    (2) Is required to cancel the certificate under another provision
of this subpart; or
    (3) Receives satisfactory evidence that the vessel is a documented
vessel or a foreign-documented vessel.

Sec.  187.309   Content of certificate of title.

    (a) A certificate of title must contain--
    (1) The date the certificate was created;
    (2) The name of the owner of record and, if not all owners are
listed, an indication that there are additional owners indicated in the
files of the office;
    (3) The mailing address of the owner of record;
    (4) The hull identification number (HIN);
    (5) The information listed in Sec.  187.307(b)(6);
    (6) Except as otherwise provided in Sec.  187.315(b), the name and
mailing address of the secured party of record, if any, and if not all
secured parties are listed, an indication that there are other security
interests indicated in the files of the office; and
    (7) All title brands indicated in the files of the office covering
the vessel, including brands indicated on a certificate created by a
governmental agency of another jurisdiction and delivered to the
office.
    (b) This subpart does not preclude the office from noting on a
certificate of title the name and mailing address of a secured party
that is not a secured party of record.
    (c) For each title brand indicated on a certificate of title, the
certificate must identify the jurisdiction under whose law the title
brand was created or the jurisdiction that created the certificate on
which the title brand was indicated. If the meaning of a title brand is
not easily ascertainable or cannot be accommodated on the certificate,
the certificate may state: ``Previously branded in (insert the
jurisdiction under whose law the title brand was created or whose
certificate of title previously indicated the title brand).''
    (d) If the files of the office indicate that a vessel was
previously registered or titled in a foreign country, the office must
indicate on the certificate of title that the vessel was registered or
titled in that country.
    (e) A written certificate of title must contain a form that all
owners indicated on the certificate may sign to evidence consent to a
transfer of an ownership interest to another person. The form must
include a certification, signed under penalty of perjury, that the
statements made are true and correct to the best of each owner's
knowledge, information, and belief.
    (f) A written certificate of title must contain a form for the
owner of record to indicate, in connection with a transfer of an
ownership interest, that the vessel is hull damaged.

Sec.  187.310   Title brand.

    (a) Unless paragraph (c) of this section applies, at or before the
time the owner of record transfers an ownership interest in a hull-
damaged vessel that is covered by a certificate of title created by the
office, if the damage occurred while that person was an owner of the
vessel and the person has notice of the damage at the time of the
transfer, the owner must--

    (1) Deliver to the office an application for a new certificate that
complies with Sec.  187.307 of this part and includes the title brand
designation ``Hull Damaged''; or
    (2) Indicate on the certificate in the place designated for that
purpose that the vessel is hull damaged and deliver the certificate to
the transferee.
    (b) Not later than 20 days after delivery to the office of the
application under paragraph (a)(1) of this section or the certificate
of title under paragraph (a)(2) of this section, the office must create
a new certificate that indicates that the vessel is branded ``Hull
Damaged''.
    (c) Before an insurer transfers an ownership interest in a hull-
damaged vessel that is covered by a certificate of title created by the
office, the insurer must deliver to the office an application for a new
certificate that complies with Sec.  187.306 and includes the title
brand designation ``Hull Damaged''. Not later than 20 days after
delivery of the application to the office, the office must create a new
certificate that indicates that the vessel is branded ``Hull Damaged''.
    (d) An owner of record who fails to comply with paragraph (a) of
this section, a person who solicits or colludes in a failure by an
owner of record to comply with paragraph (a) of this section, or an
insurer that fails to comply with paragraph (c) of this section is
subject to penalty as prescribed by state law.

Sec.  187.311   Maintenance of and access to files.

    (a) For each record relating to a certificate of title submitted to
the office, the office must--
    (1) Ascertain or assign the hull identification number (HIN) for
the vessel in accordance with 33 CFR part 181;
    (2) Maintain the HIN and all the information submitted with the
application pursuant to Sec.  187.307(b) to which the record relates,
including the date and time the record was delivered to the office;
    (3) Maintain the files for public inspection subject to paragraph
(e) of this section; and
    (4) Index the files of the office as required by paragraph (b) of
this section.
    (b) The office must maintain in its files the information contained
in all certificates of title created under this subpart. The
information in the files of the office must be searchable by the HIN of
the vessel, the vessel number, the name of the owner of record, and any
other method used by the office.
    (c) The office must maintain in its files, for each vessel for
which it has created a certificate of title, all title brands known to
the office, the name of each secured party known to the office, the
name of each person known to the office to be claiming an ownership
interest, and all stolen-property reports the office has received.
    (d) Upon request, for safety, security, or law-enforcement
purposes, the office must provide to Federal, State, or local
government the information in its files relating to any vessel for
which the office has issued a certificate of title.
    (e) Except as otherwise provided by laws of the titling State, the
information required under Sec.  187.309 is a public record, but the
information provided under Sec.  187.307(b)(3) is not a public record.

Sec.  187.312   Action required on creation of certificate of title.

    (a) On creation of a written certificate of title, the office must
promptly send the certificate to the secured party of record or, if
none, to the owner of record, at the address indicated for that person
in the files of the office. On creation of an electronic certificate of
title, the office must promptly send a record evidencing the
certificate to the owner of record and, if there is one, to the secured
party of record, at the address indicated for that person in the files
of the office. The office may send the record to the person's mailing
address or, if indicated in the files of the office, an electronic
address.
    (b) If the office creates a written certificate of title, any
electronic certificate of title for the vessel is canceled and replaced
by the written certificate. The office must maintain in the files of
the office the date and time of cancellation.
    (c) Before the office creates an electronic certificate of title,
any written certificate for the vessel must be surrendered to the
office. If the office creates an electronic certificate, the office
must destroy or otherwise cancel the written certificate for the vessel
that has been surrendered to the office and maintain in the files of
the office the date and time of destruction or other cancellation. If a
written certificate being canceled is not destroyed, the office must
indicate on the face of the certificate that it has been canceled.

Sec.  187.313   Effect of certificate of title.

    A certificate of title is prima facie evidence of the accuracy of
the information in the record that constitutes the certificate.

Sec.  187.314   Effect of possession of certificate of title; judicial
process.

    Possession of a certificate of title does not by itself provide a
right to obtain possession of a vessel. Garnishment, attachment, levy,
replevin, or other judicial process against the certificate is not
effective to determine possessory rights to the vessel. This subpart
does not prohibit enforcement under State law, other than this subpart
(33 CFR part 187 subpart D), of a security interest in, levy on, or
foreclosure of a statutory or common-law lien on a vessel. Absence of
an indication of a statutory or common-law lien on a certificate does
not invalidate the lien.

Sec.  187.315   Perfection of security interest.

    (a) Except as otherwise provided in this section or a savings
clause provided under state law, a security interest in a vessel may be
perfected only by delivery to the office of an application for a
certificate of title that identifies the secured party and otherwise
complies with Sec.  187.307. The security interest is perfected on the
later of delivery to the office of the application and the applicable
fee or attachment of the security interest as prescribed by State law
related to security interests in goods.
    (b) If the interest of a person named as owner, lessor, consignor,
or bailor in an application for a certificate of title delivered to the
office is a security interest, the application sufficiently identifies
the person as a secured party. Identification on the application for a
certificate of a person as owner, lessor, consignor, or bailor is not
by itself a factor in determining whether the person's interest is a
security interest.
    (c) If the office has created a certificate of title for a vessel,
a security interest in the vessel may be perfected by delivery to the
office of an application, on a form the office may require, to have the
security interest added to the certificate. The application must be
signed by an owner of the vessel or by the secured party and must
include--
    (1) The name of the owner of record;
    (2) The name and mailing address of the secured party;
    (3) The hull identification number (HIN) for the vessel; and
    (4) If the office has created a written certificate of title for
the vessel, the certificate.
    (d) A security interest perfected under paragraph (c) of this
section is perfected on the later of delivery to the office of the
application and all applicable fees or attachment of the security
interest as prescribed by State law related to security interests in
goods.

    (e) On delivery of an application that complies with paragraph (c)
of this section and payment of all applicable fees, the office must
create a new certificate of title pursuant to Sec.  187.308 and deliver
the new certificate or a record evidencing an electronic certificate
pursuant to Sec.  187.312(a). The office must maintain in the files of
the office the date and time of delivery of the application to the
office.
    (f) If a secured party assigns a perfected security interest in a
vessel, the receipt by the office of a statement providing the name of
the assignee as secured party is not required to continue the perfected
status of the security interest against creditors of and transferees
from the original debtor. Upon obtaining a release from the secured
party indicated in the files of the office or on the certificate, a
purchaser of a vessel subject to a security interest takes free of the
security interest and of the rights of a transferee unless the transfer
is indicated in the files of the office or on the certificate.
    (g) This section does not apply to a security interest--
    (1) Created in a vessel by a person during any period in which the
vessel is inventory held for sale or lease by the person or is leased
by the person as lessor if the person is in the business of selling
vessels;
    (2) In a barge for which no application for a certificate of title
has been delivered to the office; or
    (3) In a vessel before delivery if the vessel is under
construction, or completed, pursuant to contract and for which no
application for a certificate has been delivered to the office.
    (h) This paragraph applies if a certificate of documentation for a
documented vessel is deleted or canceled. If a security interest in the
vessel was valid immediately before deletion or cancellation against a
third party as a result of compliance with 42 U.S.C. 31321, the
security interest is and remains perfected until the earlier of 4
months after cancellation of the certificate or the time the security
interest becomes perfected under this subpart.
    (i) A security interest in a vessel arising under State law related
to security interests in goods is perfected when it attaches but
becomes unperfected when the debtor obtains possession of the vessel,
unless before the debtor obtains possession the security interest is
perfected pursuant to paragraphs (a) or (c) of this section.
    (j) A security interest in a vessel as proceeds of other collateral
is perfected to the extent provided in State law.
    (k) A security interest in a vessel perfected under the law of
another jurisdiction is perfected to the extent provided in State law.

Sec.  187.316   Termination statement.

    (a) A secured party indicated in the files of the office as having
a security interest in a vessel must deliver a termination statement to
the office and, on the debtor's request, to the debtor, by the earlier
of--
    (1) Twenty days after the secured party receives a signed demand
from an owner for a termination statement and there is no obligation
secured by the vessel subject to the security interest and no
commitment to make an advance, incur an obligation, or otherwise give
value secured by the vessel; or
    (2) If the vessel is consumer goods, 30 days after there is no
obligation secured by the vessel and no commitment to make an advance,
incur an obligation, or otherwise give value secured by the vessel.
    (b) If a written certificate of title has been created and
delivered to a secured party and a termination statement is required
under paragraph (a) of this section, the secured party, not later than
the date required by paragraph (a), must deliver the certificate to the
debtor or to the office with the statement. If the certificate is lost,
stolen, mutilated, destroyed, or is otherwise unavailable or illegible,
the secured party must deliver with the statement, not later than the
date required by paragraph (a), an application for a replacement
certificate meeting the requirements of Sec.  187.322.
    (c) On delivery to the office of a termination statement authorized
by the secured party, the security interest to which the statement
relates ceases to be perfected. If the security interest to which the
statement relates was indicated on the certificate of title, the office
must create a new certificate and deliver the new certificate or a
record evidencing an electronic certificate. The office must maintain
in its files the date and time of delivery to the office of the
statement.
    (d) A secured party that fails to comply with this section is
liable for any loss that the secured party had reason to know might
result from its failure to comply and which could not reasonably have
been prevented and for the cost of an application for a certificate of
title under Sec.  187.307 or Sec.  187.322.

Sec.  187.317   Transfer of ownership.

    (a) On voluntary transfer of an ownership interest in a vessel
covered by a certificate of title, the following rules apply:
    (1) If the certificate is a written certificate of title and the
transferor's interest is noted on the certificate, the transferor must
promptly sign the certificate and deliver it to the transferee. If the
transferor does not have possession of the certificate, the person in
possession of the certificate has a duty to facilitate the transferor's
compliance with this paragraph. A secured party does not have a duty to
facilitate the transferor's compliance with this paragraph if the
proposed transfer is prohibited by the security agreement.
    (2) If the certificate of title is an electronic certificate of
title, the transferor must promptly sign and deliver to the transferee
a record evidencing the transfer of ownership to the transferee.
    (3) The transferee has a right enforceable by specific performance
to require the transferor comply with paragraph (a)(1) or (2) of this
section.
    (b) The creation of a certificate of title identifying the
transferee as owner of record satisfies paragraph (a) of this section.
    (c) A failure to comply with paragraph (a) or to apply for a new
certificate of title does not render a transfer of ownership of a
vessel ineffective between the parties. Except as otherwise provided in
Sec.  187.318, Sec.  187.319, Sec.  187.323(a), or Sec.  187.324, a
transfer of ownership without compliance with paragraph (a) of this
section is not effective against another person claiming an interest in
the vessel.
    (d) A transferor that complies with paragraph (a) of this section
is not liable as owner of the vessel for an event occurring after the
transfer, regardless of whether the transferee applies for a new
certificate of title.

Sec.  187.318   Effect of missing or incorrect information.

    Except as otherwise provided as prescribed by State law related to
security interests in goods, a certificate of title or other record
required or authorized by this subpart is effective even if it contains
incorrect information or does not contain required information.

Sec.  187.319   Transfer of ownership by secured party's transfer
statement.

    (a) In this section, ``secured party's transfer statement'' means a
record signed by the secured party of record stating--
    (1) That there has been a default on an obligation secured by the
vessel;

    (2) The secured party of record is exercising or has exercised
post-default remedies with respect to the vessel;
    (3) By reason of the exercise, the secured party of record has the
right to transfer the ownership interest of an owner, and the name of
the owner;
    (4) The name and last known mailing address of the owner of record
and the secured party of record;
    (5) The name of the transferee;
    (6) Other information required by Sec.  187.307(b); and
    (7) One of the following:
    (i) The certificate of title is an electronic certificate;
    (ii) The secured party does not have possession of the written
certificate of title created in the name of the owner of record; or
    (iii) The secured party is delivering the written certificate of
title to the office with the secured party's transfer statement.
    (b) Unless the office rejects a secured party's transfer statement
for a reason stated in Sec.  187.308(c), not later than 20 days after
delivery to the office of the statement and payment of fees and taxes
payable under State law in connection with the statement or the
acquisition or use of the vessel, the office must--
    (1) Accept the statement;
    (2) Amend the files of the office to reflect the transfer; and
    (3) If the name of the owner whose ownership interest is being
transferred is indicated on the certificate of title--
    (i) Cancel the certificate even if the certificate has not been
delivered to the office;
    (ii) Create a new certificate indicating the transferee as owner;
and
    (iii) Deliver the new certificate or a record evidencing an
electronic certificate.
    (c) An application under paragraph (a) of this section or the
creation of a certificate of title under paragraph (b) of this section
is not by itself a disposition of the vessel and does not by itself
relieve the secured party of its duties under State law.

Sec.  187.320   Transfer by operation of law.

    (a) In this section--
    (1) ``By operation of law'' means pursuant to a law or judicial
order affecting ownership of a vessel--
    (i) Because of death, divorce or other family law proceeding,
merger, consolidation, dissolution, or bankruptcy;
    (ii) Through the exercise of the rights of a lien creditor or a
person having a lien created by statute or rule of law; or
    (iii) Through other legal process.
    (2) ``Transfer-by-law statement'' means a record signed by a
transferee stating that by operation of law the transferee has acquired
or has the right to acquire an ownership interest in a vessel.
    (b) A transfer-by-law statement must contain--
    (1) The name and last known mailing address of the owner of record
and the transferee and the other information required by Sec.
187.307(b);
    (2) Documentation sufficient to establish the transferee's
ownership interest or right to acquire the ownership interest;
    (3) A statement that--
    (i) The certificate of title is an electronic certificate of title;
    (ii) The transferee does not have possession of the written
certificate of title created in the name of the owner of record; or
    (ii) The transferee is delivering the written certificate to the
office with the transfer-by-law statement; and
    (4) Except for a transfer described in paragraph (a)(1)(i) of this
section, evidence that notification of the transfer and the intent to
file the transfer-by-law statement has been sent to all persons
indicated in the files of the office as having an interest, including a
security interest, in the vessel.
    (c) Unless the office rejects a transfer-by-law statement for a
reason stated in Sec.  187.308(c) or because the statement does not
include documentation satisfactory to the office as to the transferee's
ownership interest or right to acquire the ownership interest, not
later than 20 days after delivery to the office of the statement and
payment of fees and taxes payable under State law in connection with
the statement or with the acquisition or use of the vessel, the office
must--
    (1) Accept the statement;
    (2) Amend the files of the office to reflect the transfer; and
    (3) If the name of the owner whose ownership interest is being
transferred is indicated on the certificate of title--
    (i) Cancel the certificate even if the certificate has not been
delivered to the office;
    (ii) Create a new certificate indicating the transferee as owner;
    (iii) Indicate on the new certificate any security interest
indicated on the canceled certificate, unless a court order provides
otherwise; and
    (iv) Deliver the new certificate or a record evidencing an
electronic certificate.
    (d) This section does not apply to a transfer of an interest in a
vessel by a secured party as prescribed by State law related to
security interests in goods.

Sec.  187.321   Application for transfer of ownership or termination of
security interest without certificate of title.

    (a) Except as otherwise provided in Sec. Sec.  187.319 and 187.320,
if the office receives, unaccompanied by a signed certificate of title,
an application for a new certificate that includes an indication of a
transfer of ownership or a termination statement, the office may create
a new certificate under this section only if--
    (1) All other requirements under Sec. Sec.  187.307 and 187.308 are
met;
    (2) The applicant provides an affidavit stating facts showing that
the applicant is entitled to a transfer of ownership or termination
statement;
    (3) The applicant provides the office with satisfactory evidence
that notification of the application has been sent to the owner of
record and all persons indicated in the files of the office as having
an interest, including a security interest, in the vessel, at least 45
days have passed since the notification was sent, and the office has
not received an objection from any of those persons; and
    (4) The applicant submits any other information required by the
office as evidence of the applicant's ownership or right to terminate
the security interest, and the office has no credible information
indicating theft, fraud, or an undisclosed or unsatisfied security
interest, lien, or other claim to an interest in the vessel.
    (b) The office may indicate in a certificate of title created under
paragraph (a) of this section that the certificate was created without
submission of a signed certificate or termination statement. Unless
credible information indicating theft, fraud, or an undisclosed or
unsatisfied security interest, lien, or other claim to an interest in
the vessel is delivered to the office not later than 1 year after
creation of the certificate, on request in a form and manner required
by the office, the office must remove the indication from the
certificate.

Sec.  187.322   Replacement certificate of title.

    (a) If a written certificate of title is lost, stolen, mutilated,
destroyed, or otherwise becomes unavailable or illegible, the secured
party of record or, if no secured party is indicated in the files of
the office, the owner of record may apply for and, by furnishing
information satisfactory to the office, obtain a replacement
certificate in the name of the owner of record.
    (b) An applicant for a replacement certificate of title must sign
the application, and, except as otherwise permitted by the office, the
application

must comply with Sec.  187.307. The application must include the
existing certificate unless the certificate is lost, stolen, mutilated,
destroyed, or otherwise unavailable.
    (c) A replacement certificate of title created by the office must
comply with Sec.  187.309 and indicate on the face of the certificate
that it is a replacement certificate.
    (d) If a person receiving a replacement certificate of title
subsequently obtains possession of the original written certificate,
the person must promptly destroy the original certificate of title.

Sec.  187.323   Rights of purchaser other than secured party.

    (a) A buyer in ordinary course of business has the protections
afforded by State law even if an existing certificate of title was not
signed and delivered to the buyer or a new certificate listing the
buyer as owner of record was not created.
    (b) Except as otherwise provided in Sec. Sec.  187.317 and 187.324,
the rights of a purchaser of a vessel who is not a buyer in ordinary
course of business or a lien creditor are governed by State law.

Sec.  187.324   Rights of secured party.

    (a) Subject to paragraph (b) of this section, the effect of
perfection and non-perfection of a security interest and the priority
of a perfected or unperfected security interest with respect to the
rights of a purchaser or creditor, including a lien creditor, is
governed by State law.
    (b) If, while a security interest in a vessel is perfected by any
method under this subpart, the office creates a certificate of title
that does not indicate that the vessel is subject to the security
interest or contain a statement that it may be subject to security
interests not indicated on the certificate--
    (1) A buyer of the vessel, other than a person in the business of
selling or leasing vessels of that kind, takes free of the security
interest if the buyer, acting in good faith and without knowledge of
the security interest, gives value and receives possession of the
vessel; and
    (2) The security interest is subordinate to a conflicting security
interest in the vessel that is perfected under Sec.  187.315 after
creation of the certificate and without the conflicting secured party's
knowledge of the security interest.

Sec.  187.325   Duties and operation of office.

    (a) The office must retain the evidence used to establish the
accuracy of the information in its files relating to the current
ownership of a vessel and the information on the certificate of title.
    (b) The office must retain in its files all information regarding a
security interest in a vessel for at least 10 years after the office
receives a termination statement regarding the security interest. The
information must be accessible by the hull identification number (HIN)
for the vessel and any other methods provided by the office.
    (c) If a person submits a record to the office, or submits
information that is accepted by the office, and requests an
acknowledgment of the filing or submission, the office must send to the
person an acknowledgment showing the HIN of the vessel to which the
record or submission relates, the information in the filed record or
submission, and the date and time the record was received or the
submission accepted. A request under this section must contain the HIN
and be delivered by means authorized by the office.
    (d) The office must send or otherwise make available in a record
the following information to any person that requests it and pays the
applicable fee:
    (1) Whether the files of the office indicate, as of a date and time
specified by the office, but not a date earlier than 3 days before the
office received the request, any certificate of title, security
interest, termination statement, or title brand that relates to a
vessel--
    (i) Identified by a HIN designated in the request;
    (ii) Identified by a vessel number designated in the request; or
    (iii) Owned by a person designated in the request.
    (2) With respect to the vessel--
    (i) The name and address of any owner as indicated in the files of
the office or on the certificate of title;
    (ii) The name and address of any secured party as indicated in the
files of the office or on the certificate, and the effective date of
the information; and
    (iii) A copy of any termination statement indicated in the files of
the office and the effective date of the termination statement.
    (3) With respect to the vessel, a copy of any certificate of
origin, secured party transfer statement, transfer-by-law statement
under Sec.  187.320, and other evidence of previous or current
transfers of ownership.
    (e) In responding to a request under this section, the office may
provide the requested information in any medium. On request, the office
must send the requested information in a record that is in keeping with
State rules of evidence.

    Dated: May 31, 2022.
W.R. Arguin,
Rear Admiral, U.S. Coast Guard, Assistant Commandant for Prevention
Policy.
[FR Doc. 2022-11995 Filed 6-3-22; 8:45 am]
BILLING CODE 9110-04-P


[Federal Register Volume 81, Number 201 (Tuesday, October 18, 2016)]
[Notices]
[Pages 71737-71741]
[FR Doc No: 2016-25093]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-N-3118]

Mallinckrodt Pharmaceuticals; Proposal To Withdraw Approval of an
Abbreviated New Drug Application for Extended-Release Methylphenidate
Tablets; Opportunity for a Hearing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration's (FDA or Agency) Center for
Drug Evaluation and Research (CDER) is proposing to withdraw approval
of an abbreviated new drug application (ANDA) for methylphenidate
hydrochloride (HCl) extended-release (ER) tablets and is announcing an
opportunity for the holder of the ANDA to request a hearing on this
proposal.

DATES: Mallinckrodt Pharmaceuticals may submit a request for a hearing
by November 17, 2016. Submit all data, information, and analyses upon
which the request for a hearing relies by December 19, 2016. Submit
written or electronic comments by December 19, 2016.

ADDRESSES: The request for a hearing may be submitted by Mallinckrodt
Pharmaceuticals by either of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments to submit your request
for a hearing. Comments submitted electronically to http://www.regulations.gov, including any attachments to the request for
hearing, will be posted to the docket unchanged.

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     Because your request for a hearing will be made public,
you are solely responsible for ensuring that your request does not
include any confidential information that you may not wish to be
publicly posted, such as confidential business information, e.g., a
manufacturing process. The request for a hearing must include the
Docket No. FDA-2016-N-3118 for ``Mallinckrodt Pharmaceuticals; Proposal
to Withdraw Approval of an Abbreviated New Drug Application for
Extended-Release Methylphenidate Tablets; Opportunity for a Hearing.''
The request for a hearing will be placed in the docket and publicly
viewable at http://www.regulations.gov or at the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
    Mallinckrodt Pharmaceuticals may submit all data and analysis upon
which the request for a hearing relies in the same manner as the
request for a hearing except as follows:
     Confidential Submissions--To submit any data analyses with
confidential information that you do not wish to be made publicly
available, submit your data and analyses only as a written/paper
submission. You should submit two copies total of all data and
analyses. One copy will include the information you claim to be
confidential with a heading or cover note that states ``THIS DOCUMENT
CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy,
including the claimed confidential information, in its consideration of
any decisions on this matter. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov
or available at the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday. Submit both copies to the Division of
Dockets Management. Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law.
    Comments Submitted by Other Interested Parties: For all comments
submitted by other interested parties, submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2016-N-3118 for ``Mallinckrodt Pharmaceuticals; Proposal to
Withdraw Approval of an Abbreviated New Drug Application for Extended-
Release Methylphenidate Tablets; Opportunity for a Hearing.'' Received
comments will be placed in the docket and, except for those submitted
as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management

between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Maryll W. Toufanian, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 1716, Silver Spring, MD 20993-0002, 240-
402-7944.

SUPPLEMENTARY INFORMATION:

I. Background

A. Approval of ANDAs Referencing CONCERTA

    CONCERTA (methylphenidate HCl) ER tablet is the subject of new drug
application (NDA) 021121, held by Janssen Pharmaceuticals, Inc., and
was approved on August 1, 2000. CONCERTA is a central nervous system
stimulant intended for the treatment of attention deficit hyperactivity
disorder in children 6 years of age and older, adolescents, and adults
up to the age of 65. CONCERTA is a multiphasic modified-release product
that is formulated to release a bolus of methylphenidate, resulting in
an initial rapid rise in plasma concentration comparable to the effect
of an immediate-release (IR) methylphenidate formulation, followed by
sustained delivery later in the day, thereby allowing for once daily
dosing. The relative bioavailability of CONCERTA in adults is
comparable to IR methylphenidate administered three times daily, but
the CONCERTA formulation minimizes the fluctuations between peak and
trough concentrations associated with IR methylphenidate administered
three times daily. CONCERTA is approved for the following strengths: 18
milligrams (mg), 27 mg, 36 mg, and 54 mg. CONCERTA was approved based
on, among other things, safety studies and adequate and well-controlled
clinical efficacy studies showing that the product is safe for its
intended uses and has the effects claimed for it.
    FDA's Office of Generic Drugs (OGD) approved ANDA 202608, held by
Mallinckrodt Pharmaceuticals (Mallinckrodt), for a generic version of
CONCERTA under the requirements of section 505(j) of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 355(j)) and FDA's
implementing regulations. OGD approved ANDA 202608 on December 28,
2012, for the 27-mg, 36-mg, and 54-mg strengths.
    At the time of approval, FDA determined that the ANDA included data
sufficient to demonstrate the bioequivalence of the Mallinckrodt
product to CONCERTA. The bioequivalence (BE) testing and data submitted
in the ANDA conformed to recommendations provided in a draft guidance
for industry on ``Methylphenidate hydrochloride.'' The draft guidance
was issued on September 14, 2012 (77 FR 56851), and provided
information and recommendations for establishing bioequivalence to
CONCERTA that reflected FDA's understanding, at that time, of how to
evaluate the pharmacokinetic (PK) properties of CONCERTA to support a
demonstration of bioequivalence. The demonstration of bioequivalence
was necessary to the approval of Mallinckrodt's product. Unlike
CONCERTA, Mallinckrodt was not required to submit clinical studies to
demonstrate the safety and effectiveness of its product. Instead,
Mallinckrodt's ANDA was approved based on a finding that the product
was bioequivalent to CONCERTA and met the other requirements for ANDA
approval in section 505(j) of the FD&C Act.

B. Concerns About Insufficient Therapeutic Effect

1. ANDA 202608
    Mallinckrodt began marketing its generic version of CONCERTA in
March 2013. OGD routinely monitors all newly approved ANDA products for
safety and efficacy concerns as they penetrate the marketplace,
including the monitoring of adverse events reported to the Agency. In
May 2013, the FDA Adverse Event Reporting System (FAERS) began
receiving reports that described insufficient therapeutic effect of the
Mallinckrodt product, particularly reports describing insufficient
effect later in the day.\1\ These reports indicated potential
therapeutic inequivalence of the Mallinckrodt product as compared to
CONCERTA. In light of the reports received, CDER began an investigation
of the Mallinckrodt product.\2\
---------------------------------------------------------------------------

    \1\ In addition to reports submitted to FAERS, FDA received
complaints related to therapeutic failure from multiple other
sources, including FDA's Detroit District Office and a director of
anesthesia support at a children's hospital.
    \2\ FDA investigated ANDA 202608 concurrently with ANDA 091695,
which is another generic product referencing CONCERTA, held by
Kremers Urban Pharmaceuticals Inc. Elsewhere in this issue of the
Federal Register, FDA is proposing to withdraw approval of ANDA
091695.
---------------------------------------------------------------------------

2. CDER's Investigations
    a. Tracked safety issue (TSI). CDER began its investigation of the
Mallinckrodt product with a reevaluation of the data and information
submitted in the application to demonstrate bioequivalence; an
assessment of FAERS data; and a comparative analysis of the design,
composition, dissolution, and active pharmaceutical ingredient (API)
degradation of the generic product as compared to CONCERTA. The
findings of these investigations led to the initiation of a TSI. In
general, when CDER staff suspect that a potential safety issue could be
significant, a TSI is opened and an interdisciplinary team assesses the
safety issue, reevaluates the risk-benefit profile of the drug, and
determines the need for further action. CDER considers postmarketing
safety issues to be significant for tracking purposes if these issues
have the potential to lead to, among other things, withdrawal of FDA
approval of a drug application.
    The initial meeting of the TSI Committee occurred in December 2013.

The TSI Committee was composed of CDER physicians, pharmacists, and
chemists, as well as other CDER scientists and experts, who carefully
reviewed all of the data and information related to the Mallinckrodt
product. Key information reviewed and discussed by the TSI Committee is
summarized as follows:
     Adverse event reports. An analysis was conducted of FAERS
reports, along with additional data regarding therapeutic failure
provided by Mallinckrodt and Janssen (CONCERTA's NDA holder), to
assess, among other things, the reporting rate for therapeutic failure
for the Mallinckrodt product as compared to the reporting rate for
therapeutic failure for the authorized generic version of CONCERTA
marketed by Actavis plc.\3\ The reporting rate for therapeutic failure
was found to be 88 per 100,000 person-years of exposure for the
Mallinckrodt product and 7.0 per 100,000 person-years of exposure for
the authorized generic drug product.
---------------------------------------------------------------------------

    \3\ Authorized generic drug is defined in section 505(t) of the
FD&C Act and in Sec.  314.3(b) (21 CFR 314.3(b))  (Authorized
generic drug means a listed drug, as defined in Sec.  314.3(b), that
has been approved under section 505(c) of the FD&C Act and is
marketed, sold, or distributed directly or indirectly to retail
class of trade with labeling, packaging (other than repackaging as
the listed drug in blister packs, unit doses, or similar packaging
for use in institutions), product code, labeler code, trade name, or
trademark that differs from that of the listed drug.). A listed drug
is a new drug product that has an effective approval under section
505(c) of the FD&C Act for safety and effectiveness, or under
section 505(j), that has not been withdrawn or suspended under
section 505(e)(1) through (e)(5) or (j)(5) of the FD&C Act, and that
has not been withdrawn from sale for what FDA determines are reasons
of safety or effectiveness (Sec.  314.3(b)). Listed drugs are
identified as drugs with an effective approval in FDA's current
edition of ``Approved Drug Products With Therapeutic Equivalence
Evaluations'' (commonly referred to as the ``Orange Book'') (Id.). A
list of currently available authorized generics is available at
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm126391.htm. (FDA has
verified the Web site addresses, as of the date this document
publishes in the Federal Register, but Web sites are subject to
change over time.)
---------------------------------------------------------------------------

     Product composition. The Mallinckrodt product and CONCERTA
were tested in FDA laboratories to evaluate differences in drug design,
composition, stability, and dissolution. The testing identified
concerns with API degradation and in vivo dissolution, which could
result in differences in drug release. These differences could, in
turn, result in differences in therapeutic effect of the generic
product compared to CONCERTA.
     BE data. A review and reanalysis were conducted of the
data that were submitted in the ANDA to establish bioequivalence to
CONCERTA. In particular, an outlier analysis was performed on the BE
data to evaluate the difference in product absorption between the
Mallinckrodt product and CONCERTA across various PK sampling time
points. The analysis showed that the greatest difference in product
absorption between the Mallinckrodt product and CONCERTA occurred at 10
hours post-dosing under fasting conditions.
     Modeling of potential clinical impact. In light of the
close relationship between the PK profile and clinical effect of
methylphenidate products (Ref. 1), modeling was done based on the BE
data submitted in the ANDA to predict the potential clinical
significance of the difference in PK profile, i.e., product absorption,
of the Mallinckrodt product compared to CONCERTA. The modeling
suggested some potential clinical inequivalence between the generic
product and CONCERTA after 6 hours post-dosing. The greatest mean
percent reduction in clinical efficacy for the Mallinckrodt product is
predicted to be approximately 21 percent at 10 hours post-dosing under
fasting condition.
    The TSI was concluded in June 2014. Based on the information
considered, the TSI Committee determined that the Mallinckrodt product
may deliver methylphenidate into the body at a slower rate than
CONCERTA during the time period of 7 to 12 hours post-dosing, and
therefore, the product may not be bioequivalent or therapeutically
equivalent to CONCERTA. Following the TSI Committee's investigation,
CDER concluded that the therapeutic equivalence (TE) rating for the
Mallinckrodt product in FDA's ``Approved Drug Products with Therapeutic
Equivalence Evaluations'' (commonly referred to as the ``Orange Book'')
should be changed from AB to BX to indicate that the data are
insufficient to determine that the Mallinckrodt product is
therapeutically equivalent to CONCERTA.\4\
---------------------------------------------------------------------------

    \4\ In the Orange Book, FDA ``classifies as therapeutically
equivalent those products that meet the following general criteria:
(1) [T]hey are approved as safe and effective; (2) they are
pharmaceutical equivalents in that they (a) contain identical
amounts of the same active drug ingredient in the same dosage form
and route of administration, and (b) meet compendial or other
applicable standards of strength, quality, purity, and identity; (3)
they are bioequivalent in that (a) they do not present a known or
potential bioequivalence problem, and they meet an acceptable in
vitro standard, or (b) if they do present such a known or potential
problem, they are shown to meet an appropriate bioequivalence
standard; (4) they are adequately labeled; (5) they are manufactured
in compliance with Current Good Manufacturing Practice regulations''
(Orange Book Preface at vii, available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/UCM071436.pdf. (FDA has
verified the Web site addresses, as of the date this document
publishes in the Federal Register, but Web sites are subject to
change over time.)).
---------------------------------------------------------------------------

    On November 6, 2014 (79 FR 65978), CDER issued a revised draft
guidance for industry on ``Bioequivalence Recommendations for CONCERTA
(Methylphenidate Hydrochloride) Extended-Release Tablets'' (revised
draft BE guidance) (Ref. 2), with recommendations for establishing
bioequivalence to CONCERTA that reflect CDER's refined understanding of
the relationship between the PK profile of CONCERTA and its therapeutic
effect. The revised draft BE guidance is available on FDA's Web site
and will be placed in Docket No. FDA-2016-N-3118.
    On November 12, 2014, representatives from OGD and other CDER
offices notified Mallinckrodt by telephone of CDER's concerns regarding
its generic product. OGD explained that the TE rating for the product
would be changed from AB to BX immediately. OGD requested that
Mallinckrodt: (1) Voluntarily withdraw its product from the market
under 21 CFR 314.150(d) and request that FDA withdraw approval of the
ANDA or (2) confirm bioequivalence of its product within 6 months,
consistent with the recommendations in the revised draft BE guidance
issued on November 6, 2014. Mallinckrodt declined to voluntarily
withdraw its product from the market, and it has not submitted data or
information that confirms bioequivalence of its product to CONCERTA.
    b. Post-TSI investigation. After communicating CDER's concerns to
Mallinckrodt about its methylphenidate product and changing the TE
rating for the product to BX, CDER continued to evaluate data and
information related to the bioequivalence of Mallinckrodt's product to
CONCERTA. CDER reanalyzed the BE data originally submitted in
Mallinckrodt's ANDA in accordance with the recommendations provided in
the November 6, 2014, revised draft BE guidance. The reanalysis showed
that the 54-mg Mallinckrodt product on which the in vivo BE testing was
conducted does not provide the same extent of methylphenidate exposure
as CONCERTA during the 7- to 12-hour time period after administration.
Specifically, the 90 percent confidence interval (CI) of the geometric
mean ratio of the test product (Mallinckrodt's) to reference product
(CONCERTA) for AUC7-12 \5\ (at 64.41 percent to 72.49

percent) falls outside of the 80 percent to 125 percent BE acceptance
criteria (Ref. 4). The lower level of methylphenidate exposure compared
to CONCERTA 7 to 12 hours after administration is consistent with the
reports received describing lack of therapeutic effect later in the
day.
---------------------------------------------------------------------------

    \5\ The area under the plasma concentration-time curve (AUC) is
used to evaluate the ``extent'' of absorption of a drug. See section
505(j)(7)(B) of the FD&C Act. AUC7-12 captures the extent
of absorption from 7 to 12 hours post-dosing. See, e.g., the draft
guidance for industry entitled ``Bioequivalence Studies with
Pharmacokinetic Endpoints for Drugs Submitted under an ANDA'' (Ref.
3).
---------------------------------------------------------------------------

    In addition to the reanalysis described above, FDA performed
further clinical trial simulations based on the BE data originally
submitted in the ANDA to assess the potential clinical significance of
the difference in PK profile, i.e., methylphenidate absorption, of the
Mallinckrodt product compared to CONCERTA (Ref. 5). The simulation
suggested some potential difference in effect between Mallinckrodt's
product and CONCERTA after 6 hours post-dosing. Consistent with the
evaluation presented during the TSI, the greatest mean percent
reduction in efficacy was predicted to be 21.17 percent at 10 hours
post-dosing, with individual changes ranging from a 44.09 percent
decrease and a 9.04 percent increase in efficacy compared to CONCERTA.
    Along with a reanalysis of data submitted in the original ANDA, in
March 2015, CDER sponsored its own study to evaluate bioequivalence of
the 27-mg Mallinckrodt product as compared to CONCERTA. The CDER-
sponsored study was a single-dose, 4-treatment, fully replicated,
crossover, randomized BE study (consistent with the study design
recommended in the revised draft BE guidance) in healthy subjects under
fasting conditions. The study compared: (1) The test product--
Mallinckrodt's methylphenidate HCl ER tablets, 27 mg; and (2) the
reference product--CONCERTA ER tablets, 27 mg. A total of 28 subjects
were enrolled in the study, and 24 subjects completed all 4 periods.
Plasma samples were collected for up to 24 hours following each
treatment. The mean methylphenidate plasma concentration profiles for
both the test and reference products exhibited PK properties consistent
with those observed in the 54-mg fasting BE study submitted by
Mallinckrodt in its ANDA. In particular, decreased plasma
concentrations were observed with administration of the Mallinckrodt
product as compared to CONCERTA after 6 to 7 hours. The 90 percent CI
of the geometric mean test-to-reference ratio for AUC7-12
was below the 80 percent to 125 percent BE acceptance range (at 60.99
percent to 70.50 percent). All other metrics were found to be within
the BE acceptance range of 80 percent to 125 percent. The observed
lower level of methylphenidate exposure compared to CONCERTA 7 to 12
hours after administration is consistent with that observed in the
reanalysis of the 54-mg BE study submitted in Mallinckrodt's ANDA.
    Finally, FDA analyzed FAERS reports from February 2014 to May 2015.
The types and quality of reports received by FDA during that time
period were very similar to the reports received before FDA changed the
TE rating. The reports continued to contain specific complaints
describing the failure of therapeutic effect during the latter part of
the day.
    The applicant has not submitted data that confirms bioequivalence
of its product to CONCERTA. A memorandum describing in detail the
information considered following the TSI and explaining CDER's
determination will be placed in Docket No. FDA-2016-N-3118 (Ref. 6).

II. Conclusions and Proposed Action

    An NDA (or reference listed drug) applicant must submit ``full
reports of investigations'' to show that the drug for which the
applicant is seeking approval is safe and effective. In other words,
reference listed drugs must meet the safety and substantial evidence of
effectiveness standard (see section 505(b)(1) and (2), (c), and (d) of
the FD&C Act). A reference listed drug applicant can meet the standard
by conducting its own clinical studies (stand-alone application) or
relying, in part, on the Agency's previous finding of safety and/or
effectiveness or literature (a 505(b)(2) application). An ANDA
applicant does not submit independent clinical studies to demonstrate
safety and effectiveness. Rather, an ANDA applicant relies on the
Agency's previous finding of safety and effectiveness for the reference
listed drug and is required to meet other requirements such as
demonstrating bioequivalence to the reference listed drug to support
approval. In the absence of information showing bioequivalence between
the generic drug at issue and the reference listed drug, there is no
basis for concluding that the Agency's finding of safety and efficacy
(or substantial evidence of effectiveness) supporting approval of the
reference listed drug likewise supports approval of the generic drug.
    Therefore, based on all available data and information, notice is
given to Mallinckrodt and to all other interested persons that the
Director of CDER proposes to issue an order, under section 505(e)(3) of
the FD&C Act and Sec.  314.150(a)(2)(iii), withdrawing approval of ANDA
202608 and all amendments and supplements to it on the grounds that, on
the basis of new information, evaluated together with the evidence
available when the application was approved, there is a lack of
substantial evidence that the drug will have the effect it is
represented to have under the conditions of use prescribed,
recommended, or suggested in its labeling.

III. Hearing Procedures

    In accordance with section 505(e) of the FD&C Act, the applicant is
hereby provided an opportunity to request a hearing to show why
approval of ANDA 202608 should not be withdrawn and an opportunity to
raise, for administrative determination, all issues relating to the
legal status of the drug product covered by this application.
    An applicant who decides to seek a hearing must file the following:
(1) A written notice of participation and request for hearing (see
DATES), and (2) the data, information, and analyses relied on to
demonstrate that there is a genuine and substantial issue of fact that
requires a hearing to resolve (see DATES). Any other interested person
may also submit comments on this notice. The procedures and
requirements governing this notice of opportunity for a hearing, notice
of participation and request for a hearing, the information and
analyses to justify a hearing, other comments, and a grant or denial of
a hearing are contained in Sec.  314.200 (21 CFR 314.200) and in 21 CFR
part 12.
    The failure of an applicant to file a timely written notice of
participation and request for a hearing, as required by Sec.  314.200,
constitutes an election by that applicant not to avail itself of the
opportunity for a hearing concerning CDER's proposal to withdraw
approval of the application and constitutes a waiver of any contentions
concerning the legal status of the drug product. FDA will then withdraw
approval of the application, and the drug product may not thereafter be
lawfully introduced or delivered for introduction into interstate
commerce. Any new drug product introduced or delivered for introduction
into interstate commerce without an approved application is subject to
regulatory action at any time.
    A request for a hearing may not rest upon mere allegations or
denials, but must present specific facts showing that there is a
genuine and substantial issue of fact that requires a hearing. If a
request for a hearing is not complete or is not supported, the
Commissioner of Food and Drugs will enter summary

judgment against the person who requests the hearing, making findings
and conclusions, and denying a hearing.
    All submissions under this notice of opportunity for a hearing must
be filed in two copies. Except for data and information prohibited from
public disclosure under 21 U.S.C. 331(j) or 18 U.S.C. 1905, the
submissions may be seen in the Division of Dockets Management (see
ADDRESSES) between 9 a.m. and 4 p.m., Monday through Friday, and will
be posted to the docket at http://www.regulations.gov.
    This notice is issued under section 505(e) of the FD&C Act and
under the authority delegated to the Director of CDER by the
Commissioner of Food and Drugs.

IV. References

    The following references are on display in the Division of Dockets
Management (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also
available electronically at http://www.regulations.gov. FDA has
verified the Web site addresses, as of the date this document publishes
in the Federal Register, but Web sites are subject to change over time.

1. Swanson, J.M., et al., ``A Comparison of Once-Daily Extended-
Release Methylphenidate Formulations in Children With Attention-
Deficit/Hyperactivity Disorder in the Laboratory School (The Comacs
Study),'' Pediatrics, vol. 113, pp. 206-216, 2004.
2. FDA, draft guidance for industry, ``Bioequivalence
Recommendations for CONCERTA (Methylphenidate Hydrochloride)
Extended-Release Tablets,'' November 2014 (available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM320007.pdf).
3. FDA, draft guidance for industry, ``Bioequivalence Studies With
Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA,''
December 2013 (available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM377465).
4. Dighe, S.V. and W.P. Adams. ``Bioequivalence: A United States
Regulatory Perspective.'' In Welling, P.G., L.S. Tse, and S.V.
Dighe, eds., Pharmaceutical Bioequivalence. New York: Marcel Dekker,
Inc., pp. 347-380, 1991.
5. Kimko, H., et al., ``Population Pharmacodynamic Modeling of
Various Extended-Release Formulations of Methylphenidate in Children
With Attention Deficit Hyperactivity Disorder Via Meta-Analysis,''
Journal of Pharmacokinetics and Pharmacodynamics, vol. 39(2), pp.
161-176, 2012.
6. Memorandum to Janet Woodcock, Director, Center for Drug
Evaluation and Research, in Support of Beginning Approval Withdrawal
Proceedings for ANDA 202608 (October 1, 2016, Peters).

    Dated: October 12, 2016.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 2016-25093 Filed 10-17-16; 8:45 am]
 BILLING CODE 4164-01-P