38316 Federal Register / Vol. 83, No. 151 / Monday, August 6, 2018 / Notices 

months or more exposure over a 

lifetime. Because of the duration of use, 

the nonclinical assessment for 

marketing approval should include 

general toxicity studies, developmental 

and reproductive toxicity studies, an 

assessment of carcinogenic potential, 

and supporting toxicokinetic and 

pharmacokinetic studies. 

FDA is aware of the serious risk 

associated with smoking and is 

committed to facilitating the 

development of therapies to support 

smoking cessation efforts. This guidance 

focuses on novel components of the 

drug product formulation, heatgenerated products, and impurities that 

are generally not well characterized. 

Orally inhaled nicotine-containing 

tobacco products, including electronic 

nicotine delivery systems currently 

marketed in the United States, have 

already been associated with toxicity 

concerns (Refs 1–4). An adequate 

nonclinical assessment, as described in 

this guidance, can address the potential 

toxicity of chemicals from orally 

inhaled nicotine-containing drug 

products. As noted in the guidance, 

sponsors can use an alternative 

approach if that approach provides 

adequate safety information. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on nonclinical testing of orally inhaled 

nicotine-containing drug products. It 

does not establish any rights for any 

person and is not binding on FDA or the 

public. You can use an alternative 

approach if it satisfies the requirements 

of the applicable statutes and 

regulations. This guidance is not subject 

to Executive Order 12866. 

II. Paperwork Reduction Act of 1995 

This guidance refers to previously 

approved collections of information that 

are subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(44 U.S.C. 3501–3520). The collections 

of information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014. The collections of 

information resulting from special 

protocol assessments have been 

approved under OMB control number 

0910–0470. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at either 

https://www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/ 

Guidances/default.htm or https://

www.regulations.gov. 

IV. References 

The following reference marked with 

an asterisk (*) is on display at the 

Dockets Management Staff (see 

ADDRESSES) and is available for viewing 

by interested persons between 9 a.m. 

and 4 p.m., Monday through Friday; it 

also is available electronically at https:// 

www.regulations.gov. References 

without asterisks are not on display 

because they have copyright restriction, 

or they are available as published 

articles and books. Please contact the 

person identified in the FOR FURTHER

INFORMATION CONTACT section to 

schedule a date to inspect references 

without asterisks. 

1. Madsen, L.R., N.H. Vinther Krarup, T.K. 

Bergmann, et al., 2016, ‘‘A Cancer That 

Went Up in Smoke: Pulmonary Reaction 

to E-Cigarettes Imitating Metastatic 

Cancer,’’ Chest, 149(3):e65–67. 

2. Ghosh, A., R.C. Coakley, T. Mascenik, et 

al., 2018, ‘‘Chronic E-Cigarette Exposure 

Alters the Human Bronchial Epithelial 

Proteome,’’ American Journal of 

Respiratory and Critical Care Medicine, 

epub ahead of print February 26, 2018, 

doi: 10.1164/rccm.201710–2033OC. 

* 3. Olmedo, P., W. Goessler, S. Tanda, et al., 

2018, ‘‘Metal Concentrations in ECigarette Liquid and Aerosol Samples: 

The Contribution of Metallic Coils,’’ 

Environmental Health Perspectives, 

126(2): doi: 10.1289/EHP2175. 

4. Rubinstein, M.L., K. Delucchi, N.L. 

Benowitz, and D.E. Ramo, 2018, 

‘‘Adolescent Exposure to Toxic Volatile 

Organic Chemicals From E-Cigarettes,’’ 

Pediatrics, epub ahead of print March 5, 

2018, doi: 10.1542/peds.2017–3557. 

Dated: July 31, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–16726 Filed 8–3–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Office of the Secretary 

Findings of Research Misconduct 

AGENCY: Office of the Secretary, HHS. 

ACTION: Notice. 

SUMMARY: Notice is hereby given that on 

July 13, 2018, the U.S. Department of 

Health and Human Services (HHS) 

Debarring Official, on behalf of the 

Secretary of HHS, issued a final notice 

of debarment based on an 

Administrative Law Judge’s findings of 

research misconduct against Christian 

Kreipke, Ph.D., former Research 

Associate Professor, Wayne State 

University. Dr. Kreipke engaged in 

research misconduct in research 

supported by National Institute of 

Neurological Disorders and Stroke 

(NINDS), National Institutes of Health 

(NIH), grants R01 NS039860 and R01 

NS064976–01A2. The administrative 

actions, including five (5) years of 

debarment, were implemented 

beginning on July 13, 2018, and are 

detailed below. 

FOR FURTHER INFORMATION CONTACT: 

Wanda K. Jones, Dr.P.H., Interim 

Director, Office of Research Integrity, 

1101 Wootton Parkway, Suite 750, 

Rockville, MD 20852, (240) 453–8200. 

SUPPLEMENTARY INFORMATION: 

Christian Kreipke, Ph.D., Wayne State 

University: ORI issued a charge letter 

enumerating findings of research 

misconduct and proposing HHS 

administrative actions. Dr. Kreipke 

(‘‘Respondent’’) subsequently requested 

a hearing before an Administrative Law 

Judge (ALJ) of the Departmental Appeals 

Board to dispute these findings. A 

hearing before the ALJ was held on July 

10–12, 2017. On May 31, 2018, the ALJ 

issued his recommended decision, 

finding that Respondent recklessly 

caused or permitted twenty-three (23) 

instances of research misconduct in his 

three (3) grant applications, two (2) 

articles on which he was the first listed 

author, and two (2) posters on which he 

was the first listed author. The ALJ held 

that appropriate administrative actions 

included a five-year debarment from 

any contracting or subcontracting with 

any agency of the United States and 

from eligibility for or involvement in 

nonprocurement programs of the United 

States referred to as ‘‘covered 

transactions.’’ 2 CFR parts 180 and 376. 

The ALJ held it was an appropriate 

administrative action to also impose a 

five-year prohibition from serving in 

any capacity to the U.S. Public Health 

Service (PHS), including but not limited 

to, service on any PHS advisory 

committee, board, or peer review 

committee, or as a consultant. The ALJ 

noted that ORI also had proposed that 

the publisher of certain articles be 

notified of the need to retract those 

articles and that retraction had already 

occurred by the time of his 

recommended decision. 

Under the regulation, the ALJ’s 

recommended decision went to the 

Assistant Secretary for Health, who did 

not modify it and forwarded it to the 

HHS Debarring Official, who is the 

deciding official for the debarment. The 

ALJ decision constituted the findings of 

fact to the HHS Debarring Official in 

accordance with 2 CFR 180.845(c). On 

July 13, 2018, the HHS Debarring 

Official issued a final notice of 

debarment to begin on July 13, 2018, 

and end on July 12, 2023. 


sradovich on DSK3GMQ082PROD with NOTICES
Federal Register / Vol. 83, No. 151 / Monday, August 6, 2018 / Notices 38317 

Respondent’s grant applications, 

articles, and posters in question 

examined the differential effects of 

endothelin receptor antagonists on 

traumatic brain injury-induced 

hypoperfusion of cerebral blood flow, 

neuronal cell injury, and cognition in 

rat animal models. 

Respondent recklessly included 

falsely described images in the 

following grant applications: 

• R01 NS064976–01A1 submitted to 

NINDS, NIH (unfunded) 

• R01 NS064976–01A2 submitted to 

NINDS, NIH (funded) 

• R01 NS065824–01 submitted to 

NINDS, NIH (unfunded) 

Respondent recklessly included 

falsely described images in the 

following publications and posters: 

• ‘‘Differential effects of endothelin 

receptor A and B antagonism on 

cerebral hypoperfusion following 

traumatic brain injury.’’ Neurological 

Research 32(2):209–14, 2010 Mar 

(‘‘NR2010’’). Retracted in Neurological 

Research 39(5):472, 2017 May. 

• ‘‘Clazosentan, a novel endothelin A 

antagonist, improves cerebral blood 

flow and behavior after traumatic brain 

injury.’’ Neurological Research 

33(2):208–13, 2011 Mar (‘‘NR2011–1’’). 

Retracted in Neurological Research 

39(5):472, 2017 May. 

• 2009 poster for a Department of 

Veterans Affairs (VA) presentation: 

‘‘Using endothelin-A antagonists to 

ameliorate hypoperfusion and cognitive 

deficits following brain trauma: towards 

a clinical trial’’ (‘‘VA2009’’). 

• 2010 poster for a VA presentation: 

‘‘Endothelin-1 receptor A antagonists 

improve neurologic and cognitive 

outcome following TBI’’ (‘‘VA2010’’). 

The following findings of research 

misconduct were proven by a 

preponderance of the evidence. 

Respondent recklessly included: 

• falsely described Fluoro-Jade stained 

images of rat brain cells in: 

—Figure 8 (left panel) in R01 

NS064976–01A1 

—Figure 8B (left panel) in R01 

NS064976–01A2 

—Figures 4A–F in R01 NS065824–01 

—Figure 3 (right and left panels) in 

NR2011–1 

—Figure 5C in NR2010 

—Figure 3 (panel 3) and Figure 6 

(right and left panels) in VA2009 

—Figure 3 (panel 3) and Figure 6 

(right and left panels) in VA2010 

• falsely described systolic blood 

pressure curves in Figures 4A and 

4B in NR2010 

• falsely described cerebral blood flow 

graphs in: 

—Figure 5 (left panel) in R01 

NS064976–01A1 

—Figure 5 (left panel) in R01 

NS064976–01A2 

—Figure 3A in NR2010 

—Figure 5 in VA2009 

—Figure 5 in VA2010 

• falsely described Western blot images 

in one of the following three grant 

applications (because at least one of 

the three must be false): Figure 1 

(me+TBI panel for VEGF) in R01 

NS065824–01, Figure 2B in R01 

NS064976–01A1, and Figure 2B in 

R01 NS064976–01A2 

• falsely described Western blot images 

in: 

—Figure 2A in R01 NS064976–01A1 

—Figure 2A in R01 NS064976–01A2 

• a falsely described image of lectin 

labeled rat brain section in Figure 

2C in R01 NS065824–01 

Thus, the research misconduct 

findings set forth above became 

effective, and the following 

administrative actions have been 

implemented for a period of five (5) 

years, beginning on July 13, 2018: 

(1) Dr. Kreipke is debarred from any 

contracting or subcontracting with any 

agency of the United States Government 

and from eligibility or involvement in 

nonprocurement programs of the United 

States Government referred to as 

‘‘covered transactions’’ pursuant to 

HHS’ Implementation (2 CFR part 376) 

of Office of Management and Budget 

(OMB) Guidelines to Agencies on 

Governmentwide Debarment and 

Suspension (2 CFR part 180); and 

(2) Dr. Kreipke is prohibited from 

serving in any advisory capacity to PHS 

including, but not limited to, service on 

any PHS advisory committee, board, 

and/or peer review committee, or as a 

consultant. 

Wanda K. Jones, 

Interim Director, Office of Research Integrity. 

[FR Doc. 2018–16693 Filed 8–3–18; 8:45 am] 

BILLING CODE 4150–31–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

[Docket Number USCG–2018–0193] 

Polar Icebreaker Program; Preparation 

of Environmental Impact Statement 

AGENCY: Coast Guard, DHS. 

ACTION: Notice of Availability and 

request for comments. 

SUMMARY: The U.S. Coast Guard, as lead 

agency, announces the availability of a 

draft Programmatic Environmental 

Impact Statement (EIS) in accordance 

with the National Environmental Policy 

Act (NEPA) for the Polar Icebreaker 

Program’s design and build of up to six 

polar icebreakers. The U.S. Coast Guard 

requests public comments on the draft 

EIS. 

DATES: Comments must be submitted to 

the online docket via http://

www.regulations.gov on or before 

September 20, 2018. 

ADDRESSES: You may submit comments 

identified by docket number USCG– 

2018–0193 using the Federal portal at 

http://www.regulations.gov. See the 

‘‘Public Participation and Request for 

Comments’’ portion of the 

SUPPLEMENTARY INFORMATION section for 

further instructions on submitting 

comments. 

FOR FURTHER INFORMATION CONTACT: If 

you have questions about this notice of 

intent, email Mr. Ahmed Majumder, 

Deputy Program Manager, Polar 

Icebreaker Program, U.S. Coast Guard; 

email PIBEnvironment@uscg.mil. 

SUPPLEMENTARY INFORMATION: 

I. Table of Abbreviations 

CFR Code of Federal Regulations 

CGC Coast Guard Cutter 

EIS Environmental Impact Statement 

FR Federal Register 

NEPA National Environmental Policy Act 

PIBs Polar Icebreakers 

U.S.C. United States Code 

II. Background and Purpose 

The U.S. Coast Guard’s current fleet of 

polar icebreakers (PIBs) consists of two 

heavy icebreakers, Coast Guard Cutter 

(CGC) POLAR STAR and CGC POLAR 

SEA, and one medium icebreaker, CGC 

HEALY. The U.S. Coast Guard’s heavy 

icebreakers have both exceeded their 

designed 30 year service life. CGC 

POLAR STAR was commissioned in 

1976 and CGC POLAR SEA in 1978. 

CGC POLAR STAR began reactivation in 

2010 and completed a service life 

extension in 2013 to allow CGC POLAR 

STAR to operate for an additional seven 

to ten years. CGC POLAR SEA has 

remained out of service since 2010 and 

is not expected to be reactivated. The 

current PIB program acquisition strategy 

is approved to construct up to three 

heavy PIBs and may (at a future date) 

potentially expand to include up to 

three medium icebreakers, with planned 

service design lives of 30 years each. 

The first of these new PIBs is expected 

to delivered in 2023. Because the first 

new PIB would not be operational in the 

Polar Regions until at least 2023, new 

information may become available after 

the completion of this EIS. In that case, 

supplemental NEPA documentation 

may, as appropriate, be prepared in 


sradovich on DSK3GMQ082PROD with NOTICES