14146 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 

[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 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 

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 

mstockstill on DSK4VPTVN1PROD with NOTICES

Federal Register / Vol. 80, No. 52 / Wednesday, March 18, 2015 / Notices 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 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: 

http://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 http://

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 http://

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 

http://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 http://

www.regulations.gov under the docket 

number found in brackets in the 

heading of this document, and at FDA’s 

Web site at http://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 http://www. fda. gov/

Animal Veterinary/News Events/

WorkshopsConferences Meetings/

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 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

[USCG–2014–0941] 

Port Access Route Study: In the 

Chukchi Sea, Bering Strait and Bering 

Sea 

AGENCY: Coast Guard, DHS. 

ACTION: Notice; withdrawal. 

SUMMARY: 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. 

FOR FURTHER INFORMATION CONTACT: 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. 

SUPPLEMENTARY INFORMATION: 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 http://

www.regulations.gov and search for 

‘‘USCG–2014–0941’’. 

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 

mstockstill on DSK4VPTVN1PROD with NOTICES