Identification of Alternative In Vitro Bioequivalence Pathways Which Can Reliably Ensure In Vivo Bioequivalence of Product Performance and Quality of Non-Systemically Absorbed Drug Products for Animals; Public Meeting, 14146-14147 [2015-06119]
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Federal Register / Vol. 80, No. 52 / Wednesday, March 18, 2015 / Notices
calculation of AAC adjusted by a multiplier
of 1.1 for multiple source drugs and 1.01 for
single source drugs. In addition, this SPA
would apply a reimbursement methodology
of wholesale acquisition cost (WAC) adjusted
by a multiplier of 1.05 for state-defined
specialty therapeutic classes of drugs.
The issues to be considered at the hearing
are:
• Whether the state’s proposed increased
payment methodology under Louisiana
Medicaid SPA 12–66–B complies with the
requirements of section 1902(a)(30)(A) of the
Act which requires, in part, that states have
methods and procedures to assure that
payment rates are consistent with efficiency,
economy, and quality of care.
• Whether the state demonstrated that the
proposed payment increases are consistent
with the aggregate upper payment limits set
in implementing regulations at 42 CFR
447.512 which provide that payments for
drugs are to be based on the lower of: 1) the
ingredient EAC of the drug and a reasonable
dispensing fee; or 2) the provider’s usual and
customary charges to the general public.
• Whether the proposed calculation of
EAC used in calculating upper payment
limits (based on a multiple of the AAC) is
consistent with the definition of EAC in 42
CFR 447.502, which defines EAC as ‘‘the
agency’s best estimate of the price generally
and currently paid by providers for a drug
marketed or sold by a particular
manufacturer or labeler in the package size
of drug most frequently purchased by
providers.’’
In the event that CMS and the state come
to agreement on resolution of the issues
which formed the basis for disapproval, this
SPA may be moved to approval prior to the
scheduled hearing.
Sincerely,
Andrew M. Slavitt
Section 1116 of the Social Security Act (42
U.S.C. 1316; 42 CFR 430.18) (Catalog of
Federal Domestic Assistance program No.
13.714. Medicaid Assistance Program.)
Dated: March 13, 2015.
Andrew M. Slavitt,
Acting Administrator, Centers for Medicare
& Medicaid Services.
[FR Doc. 2015–06226 Filed 3–17–15; 8:45 am]
BILLING CODE 4120–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
mstockstill on DSK4VPTVN1PROD with NOTICES
[Docket No. FDA–2015–N–0684]
Identification of Alternative In Vitro
Bioequivalence Pathways Which Can
Reliably Ensure In Vivo Bioequivalence
of Product Performance and Quality of
Non-Systemically Absorbed Drug
Products for Animals; Public Meeting
AGENCY:
Food and Drug Administration,
HHS.
VerDate Sep<11>2014
19:00 Mar 17, 2015
Jkt 235001
Notification of public meeting;
request for comments.
ACTION:
The Food and Drug Administration
(FDA) is announcing a public meeting
entitled ‘‘Identification of Alternative In
Vitro Bioequivalence Pathways Which
Can Reliably Ensure In Vivo
Bioequivalence of Product Performance
and Quality of Non-Systemically
Absorbed Drug Products for Animals’’.
The purpose of the public meeting is to
discuss the use of in vitro methods as
a mechanism for assessing the in vivo
product bioequivalence (BE) of nonsystemically absorbed drug products
intended for use in veterinary species.
FDA is seeking additional public
comment to the docket, and is
requesting that any written comments
be submitted by May 18, 2015.
Date and Time: The public meeting
will be held on April 16, 2015, from 9
a.m. to 4 p.m.
Location: The public meeting will be
held at the Center for Veterinary
Medicine (CVM), Food and Drug
Administration, 7519 Standish Pl., 3rd
Floor, Conference Room A, Rockville,
MD 20855. Parking is free.
Contact Person: Aleta Sindelar, CVM,
Food and Drug Administration, 7519
Standish Pl., Rm. 144, Rockville, MD
20855, 240–276–9230, FAX: 240–276–
9241, email: BioequivalencePublic
MeetingRegistration@fda.hhs.gov.
Registration: Registration is free and
available on a first-come, first-served
basis. Persons interested in requesting
an opportunity to speak during the open
public comment period must register by
April 8, 2015, and must include a brief
summary of comments with their
registration. Those individuals will be
contacted prior to the meeting regarding
their participation. Persons interested in
attending this meeting who are not
requesting an opportunity to speak at
the meeting must register by April 14,
2015. For general questions about the
meeting, for assistance registering for
the meeting, to request an opportunity
to make an oral presentation, or to
request special accommodations due to
a disability, contact Aleta Sindelar (see
Contact Person). Please include your
name, organization, and contact
information. Early registration for the
meeting is encouraged due to limited
time and space.
SUPPLEMENTARY INFORMATION:
I. Background
Given the imprecision and logistic
challenges associated with clinical
endpoint BE studies, FDA is exploring
alternative pathways that can be applied
to help ensure the equivalence of
product performance and quality for
PO 00000
Frm 00077
Fmt 4703
Sfmt 4703
those products that are non-systemically
absorbed (locally acting).
The assessment of in vivo BE of nonsystemically absorbed drug products has
been a longstanding challenge facing
drug manufacturers and regulators of
human and animal health products.
Although blood level BE trials remain
the standard for comparing drug
products that are systemically absorbed
and that act at a target site reached via
the blood (systemic circulation), such
studies cannot confirm product in vivo
BE when a drug is either not
systemically absorbed or when it is
associated with therapeutic effects
occurring proximal to the site of
absorption. To date, unless the active
pharmaceutical ingredient met the
criteria for highly soluble, as defined in
CVM Guidance #171 entitled ‘‘Waivers
of In Vivo Demonstration of
Bioequivalence of Animal Drugs in
Soluble Powder Oral Dosage Form
Products and Type A Medicated
Articles,’’ clinical endpoint BE trials
have provided the only option for
generating inter-product comparisons.
FDA is exploring whether an alternative
in vitro BE approach may be considered
when blood level BE studies are either
not feasible or not appropriate, and
when products do not meet the criteria
for applying a Guidance #171-based
biowaiver.
The assumption underlying the
application of the in vitro BE approach
is that equivalence in product
physicochemical attributes and in vitro
product performance translates to
equivalence in product in vivo behavior.
For sponsors with a right of reference to
underlying safety and effectiveness data,
the criteria for similarity of
physicochemical attributes would be
defined on the basis of the underlying
dataset to confirm the comparability of
the original formulation and pre- and
post-approval changes in formulation or
method of product manufacture. In the
case of generic products, a more rigid
approach to sameness would be used in
terms of product composition and
physicochemical characteristics. In both
situations, physicochemical
comparisons would be based upon a
battery of in vitro test procedures,
including a comparison of in vitro
dissolution behavior under a range of
physiologically-relevant conditions.
Examples of the kinds of products
where in vitro bioequivalence concepts
can potentially be applied include some
orally administered products (e.g., Type
A medicated articles), solutions,
emulsions, ointments, creams,
suspensions, transdermal products, and
intra-mammary formulations. Due to
unique issues raised by products
E:\FR\FM\18MRN1.SGM
18MRN1
Federal Register / Vol. 80, No. 52 / Wednesday, March 18, 2015 / Notices
mstockstill on DSK4VPTVN1PROD with NOTICES
employing modified release
technologies, only immediate release
formulations would be candidates for
the in vitro BE assessment. For orally
administered products, in vitro BE
would be limited to disintegrated
dosage forms. In cases when the
administered drug acts both locally and
systemically, blood level data may be
used to confirm drug product BE of the
systemic effects (and to confirm
comparability of in vivo product
disintegration in cases where multiple
drugs are combined in a single solid oral
dosage forms), while the additional in
vitro dissolution data could be used to
support the comparability of the local
actions.
The in vitro BE approach should not
be construed as a biowaiver, but rather
as an alternative set of tests that would
be handled in a manner consistent with
that of an in vivo BE study. Specifically,
(1) because an in vitro BE approach is
not a biowaiver, sponsors would still
need to meet the same environmental
safety and human food safety
requirements associated with products
undergoing in vivo BE studies; (2) one
in vitro study may not suffice when
there are multiple product strengths
(e.g., varying concentrations of an intramammary infusion); and (3) the in vitro
method could be applied both to fully
soluble and poorly soluble compounds.
In vitro BE determinations would be
based upon a battery of in vitro
dissolution studies and
physicochemical tests. Links to
additional background material are
provided on the Agency’s Web site at:
https://www.fda.gov/AnimalVeterinary/
NewsEvents/WorkshopsConferences
Meetings/ucm435459.htm.
To assist FDA in developing guidance
for demonstrating in vitro BE, with this
notice the Agency is convening an open
forum, providing a summary of what the
Agency envisions as considerations
pivotal to the BE assessment and
inviting public comment on the various
components of an in vitro BE
determination.
II. Participation in a Public Meeting
While oral presentations from specific
individuals and organizations may be
limited due to time constraints during
the public meeting, stakeholders may
submit electronic or written comments
discussing any issues of concern to the
administrative record (the docket) for
the rulemaking. All relevant data and
documentation should be submitted
with the comments. Submit electronic
comments to https://
www.regulations.gov. Submit written
comments to the Division of Dockets
Management (HFA–305), Food and Drug
VerDate Sep<11>2014
19:00 Mar 17, 2015
Jkt 235001
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. It is only
necessary to send one set of comments.
Identify comments with the docket
number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday, and
will be posted to the docket at https://
www.regulations.gov.
III. Comments, Transcripts, and
Recorded Video
Information and data submitted
voluntarily to FDA during the public
meeting will become part of the
administrative record for the rulemaking
and will be accessible to the public at
https://www.regulations.gov. The
transcript of the proceedings from the
public meeting will become part of the
administrative record for the
rulemaking. Please be advised that as
soon as a transcript is available, it will
be accessible at https://
www.regulations.gov under the docket
number found in brackets in the
heading of this document, and at FDA’s
Web site at https://www. fda. gov/
AnimalVeterinary/NewsEvents/
WorkshopsConferencesMeetings/
ucm435459.htm. It may also be viewed
at the Division of Dockets Management
(HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. A transcript
will also be available in either hardcopy
or on CD–ROM, after submission of a
Freedom of Information request. Written
requests are to be sent to the Division
of Freedom of Information (ELEM–
1029), Food and Drug Administration,
12420 Parklawn Dr., Element Bldg.,
Rockville, MD 20857.
Additionally, the public can access
the meeting remotely by using the
following Adobe Connect link: https://
collaboration. fda. gov/cvm_
bioequivalence_meeting/. The link will
become active shortly before the
meeting begins at 9 a.m. on April 16,
2015. Anyone interested in viewing the
meeting remotely using this link will
need to register as a guest using the
registration information in this
document. The Agency will be
recording the meeting for subsequent
viewing by the public. Once the
recording has been made 508 compliant,
it will be accessible at FDA’s CVM Web
site at https://www. fda. gov/
Animal Veterinary/News Events/
WorkshopsConferences Meetings/
ucm435459.htm.
PO 00000
Frm 00078
Fmt 4703
Sfmt 9990
14147
Dated: March 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015–06119 Filed 3–17–15; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HOMELAND
SECURITY
Coast Guard
[USCG–2014–0941]
Port Access Route Study: In the
Chukchi Sea, Bering Strait and Bering
Sea
AGENCY:
ACTION:
Coast Guard, DHS.
Notice; withdrawal.
The Coast Guard published a
document in the Federal Register of
February 19, 2015, (80 FR 8892)
concerning the Port Access Route Study
(PARS) in the Chukchi Sea, Bering Strait
and Bering Sea. The February 19, 2015,
PARS document was erroneously
published and should be disregarded in
its entirety.
SUMMARY:
If
you have questions on this notice of
study or any of the meetings, call or
email LT Kody Stitz, Seventeenth Coast
Guard District (dpw); telephone (907)
463–2270; email Kody.J.Stitz@uscg.mil
or Mr. David Seris, Seventeenth Coast
Guard District (dpw); telephone (907)
463–2267; email David.M.Seris@
uscg.mil.
FOR FURTHER INFORMATION CONTACT:
For
correct information on the Port Access
Route Study please see the Notice of
Study published in the Federal Register
on December 5, 2014 (79 FR 72157); and
the Notice of Public Meetings published
in the Federal Register on February 25,
2015 (80 FR 10137).
To electronically access all
information referenced in this notice of
correction visit https://
www.regulations.gov and search for
‘‘USCG–2014–0941’’.
SUPPLEMENTARY INFORMATION:
Dated: March 3, 2015.
D.B. Abel,
Rear Admiral, U.S. Coast Guard, Commander,
Seventeenth Coast Guard District.
[FR Doc. 2015–05372 Filed 3–17–15; 8:45 am]
BILLING CODE 9110–04–P
E:\FR\FM\18MRN1.SGM
18MRN1
]]>Agencies
[Federal Register Volume 80, Number 52 (Wednesday, March 18, 2015)]
[Notices]
[Pages 14146-14147]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-06119]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2015-N-0684]
Identification of Alternative In Vitro Bioequivalence Pathways
Which Can Reliably Ensure In Vivo Bioequivalence of Product Performance
and Quality of Non-Systemically Absorbed Drug Products for Animals;
Public Meeting
AGENCY: Food and Drug Administration, HHS.
ACTION: Notification of public meeting; request for comments.
-----------------------------------------------------------------------
The Food and Drug Administration (FDA) is announcing a public
meeting entitled ``Identification of Alternative In Vitro
Bioequivalence Pathways Which Can Reliably Ensure In Vivo
Bioequivalence of Product Performance and Quality of Non-Systemically
Absorbed Drug Products for Animals''. The purpose of the public meeting
is to discuss the use of in vitro methods as a mechanism for assessing
the in vivo product bioequivalence (BE) of non-systemically absorbed
drug products intended for use in veterinary species. FDA is seeking
additional public comment to the docket, and is requesting that any
written comments be submitted by May 18, 2015.
Date and Time: The public meeting will be held on April 16, 2015,
from 9 a.m. to 4 p.m.
Location: The public meeting will be held at the Center for
Veterinary Medicine (CVM), Food and Drug Administration, 7519 Standish
Pl., 3rd Floor, Conference Room A, Rockville, MD 20855. Parking is
free.
Contact Person: Aleta Sindelar, CVM, Food and Drug Administration,
7519 Standish Pl., Rm. 144, Rockville, MD 20855, 240-276-9230, FAX:
240-276-9241, email:
BioequivalencePublicMeetingRegistration@fda.hhs.gov.
Registration: Registration is free and available on a first-come,
first-served basis. Persons interested in requesting an opportunity to
speak during the open public comment period must register by April 8,
2015, and must include a brief summary of comments with their
registration. Those individuals will be contacted prior to the meeting
regarding their participation. Persons interested in attending this
meeting who are not requesting an opportunity to speak at the meeting
must register by April 14, 2015. For general questions about the
meeting, for assistance registering for the meeting, to request an
opportunity to make an oral presentation, or to request special
accommodations due to a disability, contact Aleta Sindelar (see Contact
Person). Please include your name, organization, and contact
information. Early registration for the meeting is encouraged due to
limited time and space.
SUPPLEMENTARY INFORMATION:
I. Background
Given the imprecision and logistic challenges associated with
clinical endpoint BE studies, FDA is exploring alternative pathways
that can be applied to help ensure the equivalence of product
performance and quality for those products that are non-systemically
absorbed (locally acting).
The assessment of in vivo BE of non-systemically absorbed drug
products has been a longstanding challenge facing drug manufacturers
and regulators of human and animal health products. Although blood
level BE trials remain the standard for comparing drug products that
are systemically absorbed and that act at a target site reached via the
blood (systemic circulation), such studies cannot confirm product in
vivo BE when a drug is either not systemically absorbed or when it is
associated with therapeutic effects occurring proximal to the site of
absorption. To date, unless the active pharmaceutical ingredient met
the criteria for highly soluble, as defined in CVM Guidance #171
entitled ``Waivers of In Vivo Demonstration of Bioequivalence of Animal
Drugs in Soluble Powder Oral Dosage Form Products and Type A Medicated
Articles,'' clinical endpoint BE trials have provided the only option
for generating inter-product comparisons. FDA is exploring whether an
alternative in vitro BE approach may be considered when blood level BE
studies are either not feasible or not appropriate, and when products
do not meet the criteria for applying a Guidance #171-based biowaiver.
The assumption underlying the application of the in vitro BE
approach is that equivalence in product physicochemical attributes and
in vitro product performance translates to equivalence in product in
vivo behavior. For sponsors with a right of reference to underlying
safety and effectiveness data, the criteria for similarity of
physicochemical attributes would be defined on the basis of the
underlying dataset to confirm the comparability of the original
formulation and pre- and post-approval changes in formulation or method
of product manufacture. In the case of generic products, a more rigid
approach to sameness would be used in terms of product composition and
physicochemical characteristics. In both situations, physicochemical
comparisons would be based upon a battery of in vitro test procedures,
including a comparison of in vitro dissolution behavior under a range
of physiologically-relevant conditions.
Examples of the kinds of products where in vitro bioequivalence
concepts can potentially be applied include some orally administered
products (e.g., Type A medicated articles), solutions, emulsions,
ointments, creams, suspensions, transdermal products, and intra-mammary
formulations. Due to unique issues raised by products
[[Page 14147]]
employing modified release technologies, only immediate release
formulations would be candidates for the in vitro BE assessment. For
orally administered products, in vitro BE would be limited to
disintegrated dosage forms. In cases when the administered drug acts
both locally and systemically, blood level data may be used to confirm
drug product BE of the systemic effects (and to confirm comparability
of in vivo product disintegration in cases where multiple drugs are
combined in a single solid oral dosage forms), while the additional in
vitro dissolution data could be used to support the comparability of
the local actions.
The in vitro BE approach should not be construed as a biowaiver,
but rather as an alternative set of tests that would be handled in a
manner consistent with that of an in vivo BE study. Specifically, (1)
because an in vitro BE approach is not a biowaiver, sponsors would
still need to meet the same environmental safety and human food safety
requirements associated with products undergoing in vivo BE studies;
(2) one in vitro study may not suffice when there are multiple product
strengths (e.g., varying concentrations of an intra-mammary infusion);
and (3) the in vitro method could be applied both to fully soluble and
poorly soluble compounds. In vitro BE determinations would be based
upon a battery of in vitro dissolution studies and physicochemical
tests. Links to additional background material are provided on the
Agency's Web site at: https://www.fda.gov/AnimalVeterinary/NewsEvents/WorkshopsConferencesMeetings/ucm435459.htm.
To assist FDA in developing guidance for demonstrating in vitro BE,
with this notice the Agency is convening an open forum, providing a
summary of what the Agency envisions as considerations pivotal to the
BE assessment and inviting public comment on the various components of
an in vitro BE determination.
II. Participation in a Public Meeting
While oral presentations from specific individuals and
organizations may be limited due to time constraints during the public
meeting, stakeholders may submit electronic or written comments
discussing any issues of concern to the administrative record (the
docket) for the rulemaking. All relevant data and documentation should
be submitted with the comments. Submit electronic comments to https://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852. It is only necessary to send one set of
comments. Identify comments with the docket number found in brackets in
the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday, and will be posted to the docket at https://www.regulations.gov.
III. Comments, Transcripts, and Recorded Video
Information and data submitted voluntarily to FDA during the public
meeting will become part of the administrative record for the
rulemaking and will be accessible to the public at https://www.regulations.gov. The transcript of the proceedings from the public
meeting will become part of the administrative record for the
rulemaking. Please be advised that as soon as a transcript is
available, it will be accessible at https://www.regulations.gov under
the docket number found in brackets in the heading of this document,
and at FDA's Web site at https://www.fda.gov/AnimalVeterinary/NewsEvents/WorkshopsConferencesMeetings/ucm435459.htm. It may also be
viewed at the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. A
transcript will also be available in either hardcopy or on CD-ROM,
after submission of a Freedom of Information request. Written requests
are to be sent to the Division of Freedom of Information (ELEM-1029),
Food and Drug Administration, 12420 Parklawn Dr., Element Bldg.,
Rockville, MD 20857.
Additionally, the public can access the meeting remotely by using
the following Adobe Connect link: https://collaboration. fda. gov/
cvm_bioequivalence_meeting/. The link will become active shortly before
the meeting begins at 9 a.m. on April 16, 2015. Anyone interested in
viewing the meeting remotely using this link will need to register as a
guest using the registration information in this document. The Agency
will be recording the meeting for subsequent viewing by the public.
Once the recording has been made 508 compliant, it will be accessible
at FDA's CVM Web site at https://www.fda.gov/AnimalVeterinary/NewsEvents/WorkshopsConferencesMeetings/ucm435459.htm.
Dated: March 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-06119 Filed 3-17-15; 8:45 am]
BILLING CODE 4164-01-P
