42896 Federal Register / Vol. 83, No. 165 / Friday, August 24, 2018 / Notices 

ANNUAL BURDEN ESTIMATES—Continued 

Instrument Number of 

respondents 

Number of 

responses per 

respondent 

Average 

burden hours 

per response 

Total burden 

hours 

Letter of Designation ....................................................................................... 25,000 1 0.5 12,500

Estimated Total Annual Burden per 

Respondent: 207,500. 

Additional Information: Copies of the 

proposed collection may be obtained by 

writing to the Administration for 

Children and Families, Office of 

Planning, Research and Evaluation, 330 

C Street SW, Washington, DC 20201. 

Attention Reports Clearance Officer. All 

requests should be identified by the title 

of the information collection. Email 

address: infocollection@acf.hhs.gov. 

OMB Comment: OMB is required to 

make a decision concerning the 

collection of information between 30 

and 60 days after publication of this 

document in the Federal Register. 

Therefore, a comment is best assured of 

having its full effect if OMB receives it 

within 30 days of publication. Written 

comments and recommendations for the 

proposed information collection should 

be sent directly to the following: Office 

of Management and Budget, Paperwork 

Reduction Project, Email: OIRA_

SUBMISSION@OMB.EOP.GOV, Attn: 

Desk Officer for the Administration for 

Children and Families. 

Robert A. Sargis, 

Reports Clearance Officer. 

[FR Doc. 2018–18351 Filed 8–23–18; 8:45 am] 

BILLING CODE 4184–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–N–0567] 

Notice of Decision Not To Designate 

Pneumocystis Pneumonia as a 

Tropical Disease 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency), in 

response to suggestions submitted to 

Docket No. FDA–2008–N–0567, has 

analyzed whether Pneumocystis 

pneumonia (PCP) meets the statutory 

criteria for designation as a tropical 

disease for the purposes of obtaining a 

priority review voucher (PRV) under the 

Federal Food, Drug, and Cosmetic Act 

(FD&C Act), namely whether it 

primarily affects poor and marginalized 

populations and whether there is ‘‘no 

significant market’’ for drugs that 

prevent or treat PCP in developed 

countries. The Agency has determined 

that PCP does not meet the statutory 

criteria for designation as a tropical 

disease and declines to designate it as 

such. 

DATES: August 24, 2018. 

ADDRESSES: Submit electronic 

comments on additional diseases 

suggested for designation to https://

www.regulations.gov. Submit written 

comments on additional diseases 

suggested for designation to the Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

All comments should be identified with 

the docket number found in brackets in 

the heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Katherine Schumann, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 22, Rm. 6242, 

Silver Spring, MD 20993–0002, 301– 

796–1300, Katherine.Schumann@

fda.hhs.gov; or Office of 

Communication, Outreach and 

Development (OCOD), Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Silver Spring, MD 

20993–0002, 800–835–4709 or 240– 

402–8010, ocod@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. Background: Priority Review Voucher 

Program 

II. Decision Not To Designate Pneumocystis 

Pneumonia 

A. Significant Market in Developed 

Nations 

B. Disproportionately Affects Poor and 

Marginalized Populations 

C. FDA Determination 

III. Process for Requesting Additional 

Diseases To Be Added to the List 

IV. Paperwork Reduction Act 

V. References 

I. Background: Priority Review 

Voucher Program 

Section 524 of the FD&C Act (21 

U.S.C. 360n), which was added by 

section 1102 of the Food and Drug 

Administration Amendments Act of 

2007 (FDAAA), uses a PRV incentive to 

encourage the development of new 

drugs, including biologics, for 

prevention and treatment of certain 

diseases that, in the aggregate, affect 

millions of people throughout the 

world. Further information about the 

tropical disease PRV program can be 

found in guidance for industry 

‘‘Tropical Disease Priority Review 

Vouchers’’ (81 FR 69537, October 6, 

2016, available at https://

www.federalregister.gov/documents/ 

2015/08/20/2015-20554/designatingadditions-to-the-current-list-of-tropicaldiseases-in-the-federal-food-drug-andcosmetic). Additions to the statutory list 

of tropical diseases published in the 

Federal Register can be accessed at 

https://www.fda.gov/AboutFDA/Centers

Offices/OfficeofMedicalProducts

andTobacco/CDER/ucm534162.htm. 

In August 2015, FDA published a 

final order (80 FR 50559, August 20, 

2015) (final order) designating Chagas 

disease and neurocysticercosis as 

tropical diseases. That final order also 

sets forth FDA’s interpretation of the 

statutory criteria for tropical disease 

designation and expands the list of 

tropical diseases under section 

524(a)(3)(R) of the FD&C Act, which 

authorizes the FDA to designate by 

order ‘‘[a]ny other infectious disease for 

which there is no significant market in 

developed nations and that 

disproportionately affects poor and 

marginalized populations’’ as a tropical 

disease. 

FDA has applied its August 2015 

criteria as set forth in the final order to 

analyze whether PCP meets the 

statutory criteria for addition to the 

tropical disease list. As discussed 

below, the Agency has determined that 

PCP does not meet the statutory criteria 

for designation as a ‘‘tropical disease’’ 

and thus will not add it to the list of 

tropical diseases whose applications 

may be eligible for a priority review 

voucher. 

II. Decision Not To Designate 

Pneumocystis Pneumonia 

FDA has considered all diseases 

submitted to the public docket (FDA– 

2008–N–0567) between August 20, 

2015, and June 20, 2018, as potential 

additions to the list of tropical diseases 

under section 524 of the FD&C Act, 

under the docket review process 

explained on the Agency’s website (see 


daltland on DSKBBV9HB2PROD with NOTICES
Federal Register / Vol. 83, No. 165 / Friday, August 24, 2018 / Notices 42897 

https://www.fda.gov/AboutFDA/Centers

Offices/OfficeofMedicalProductsand

Tobacco/CDER/ucm534162.htm). Based 

on an assessment using the criteria from 

its final order, FDA has determined that 

PCP will not be designated as a 

‘‘tropical disease’’ under section 524 of 

the FD&C Act. 

Pneumocystis species are genetically 

distinct, host-specific opportunistic 

fungal pathogens widely found in 

nature. Pneumocystis jirovecii, found in 

humans, causes PCP in 

immunocompromised patients. Human 

immunodeficiency virus (HIV)-infected 

patients with a low CD4 count are at the 

highest risk of PCP. Others at substantial 

risk include hematopoietic cell and 

solid organ transplant recipients, those 

with cancer (particularly hematologic 

malignancies), and those receiving 

glucocorticoids, chemotherapeutic 

agents, and other immunosuppressive 

medications. Among patients with 

acquired immunodeficiency syndrome 

(AIDS) and PCP, the mortality rate is 10 

to 20 percent during the initial 

infection, but the rate increases 

substantially when the patient requires 

mechanical ventilation. The mortality 

rate among patients with PCP in the 

absence of AIDS is 30 to 60 percent, 

depending on the population at risk, 

with a greater risk of death among 

patients with cancer than among 

patients undergoing transplantation or 

those with connective tissue disease 

(Ref. 1). 

A. Significant Market in Developed 

Nations 

In developed nations, a sizable market 

exists for PCP prophylaxis drugs. The 

prevalence of stage-3 AIDS by year end 

2014 in the United States (i.e., with 

AIDS requiring PCP prophylaxis) was 

approximately 530,000 (Ref 2). In 

addition, approximately 30,000 solid 

organ transplantations (Ref. 3) and 

19,000 hematopoietic stem cell 

transplants (Ref. 4) are performed 

annually in the United States. These 

patients receive PCP prophylaxis for 6 

months to one year in the posttransplantation period. There were also 

about 6,590 new cases of acute 

lymphocytic leukemia (ALL) eligible for 

PCP prophylaxis in the United States in 

2016 (Ref. 5). 

Regarding treatment of PCP, the 

incidence of PCP has declined 

substantially with widespread use of 

PCP prophylaxis and anti-retroviral 

therapy (ART) (see, e.g., Refs. 6–9). In a 

prospective cohort study of 8070 

participants at 12 HIV clinics across the 

United States, the incidence in 2003– 

2007 was <1 case per 100 person-years 

(Ref. 10). PCP now mainly occurs in 

individuals who are unaware that they 

are HIV positive, lack access to medical 

care, or are noncompliant with 

medications. 

In contrast to HIV-positive patients, 

the incidence of PCP in non-HIV 

patients is rising in some areas (see, e.g., 

Refs. 8, 9, 11); however, the number of 

cases in non-HIV patients is still below 

the number of cases in HIV-positive 

patients (Ref. 12). In the United States, 

the incidence of PCP is estimated to be 

9 percent among hospitalized HIV/AIDS 

patients and 1 percent among solid 

organ transplant recipients (Ref. 13). 

Current clinical guidelines 

recommend chemoprophylaxis against 

primary PCP for HIV infected persons 

with a CD4 cell count <200 cells/mL or 

a history of oral candidiasis (Ref. 14). As 

indicated above, the prevalence of stage3 HIV infection (i.e., AIDS requiring PCP 

prophylaxis) by year end 2014 in the 

United States was approximately 

530,000 patients, including 18,303 

patients diagnosed with stage-3 HIV 

infection in 2015 (Ref. 2). These subjects 

were eligible for PCP prophylaxis. 

In summary, a sizable market in 

developed nations exists for drugs 

indicated for prevention of PCP. At 

present, FDA is unaware of any 

significant funding by military, the 

Biomedical Advanced Research and 

Development Authority (BARDA), or 

any other United States Government 

sources for drug development targeting 

treatment of or prophylaxis against PCP. 

B. Disproportionately Affects Poor and 

Marginalized Populations 

Although no disability-adjusted life 

year (DALY) data were found to 

distinguish the disease burden of PCP in 

developing versus developed countries, 

it is noted that PCP occurs frequently 

among HIV-infected patients in many 

parts of the developing world. In 

addition, the prevalence of HIV-infected 

persons with PCP ranges from 24 

percent (42/177) in Mexico (Ref. 15) to 

55 percent in Thailand (Ref. 16). A 

Brazilian study found 55 percent (15/27) 

of HIV-infected persons with respiratory 

symptoms had PCP (Ref. 17). 

Studies estimating the burden of 

fungal infections in different countries 

suggest low total yearly number of PCP 

cases in Belgium (n = 120), in contrast, 

for example, to 9,600 cases among HIVinfected people in Tanzania in 2012 

(Refs. 18 and 19). In Uganda, the 

frequency of PCP among HIV-infected 

patients hospitalized with suspected 

pneumonia who had negative sputum 

acid-fast bacilli smears and underwent 

bronchoscopy decreased from nearly 40 

percent of bronchoscopies between 1999 

and 2000 to less than ten percent 

between 2007 and 2008 (Ref. 20). 

However, it is estimated that there are 

approximately 800 HIV-positive adults 

with PCP annually and up to 42,000 

children with PCP annually in Uganda 

(Ref. 21). In Vietnam, the prevalence of 

PCP was 608 cases in 2012, 1149 cases 

per year in Senegal and 990 cases yearly 

in Nepal (HIV positive individuals) 

(Refs. 22, 23, 24). In Ukraine, 13.5 per 

100,000 individuals develop PCP 

annually (Ref. 25). 

High rates of anti-Pneumocystis 

antibodies among African children 

suggest that exposure to the organism is 

common, and that Pneumocystis 

jirovecii is a common cause of 

pneumonia among children in subSaharan Africa (Ref. 26). Furthermore, 

limited diagnostic resources and less 

commonly performed induced sputum 

and bronchoalveolar lavage with 

reliance on empiric therapy may cause 

underestimation of the true incidence of 

PCP (Ref. 27). Several studies suggest 

that the incidence of PCP is increasing 

in Africa (Refs. 26, 28, 29). 

PCP has been reported to be a leading 

cause of death in HIV-infected infants, 

responsible for at least one quarter of all 

pneumonia deaths in HIV-infected 

infants (Ref. 30). A recent review found 

PCP to be one of the factors strongly 

associated with mortality from acute 

lower respiratory infections in children 

under five years of age in low-income 

economies, lower-middle-income 

economies, and upper-middle-income 

economies (referred to as low- and 

middle-income countries (LMICs)), with 

odds ratio of 95 percent confidence 

interval of 4.79, 2.67–8.61 (Ref. 31). 

However, the incidence of PCP in 

infants and children in developed 

countries has decreased because PCP 

prophylaxis has been initiated in all 

neonates born to HIV-positive mothers 

(Refs. 32 and 33). 

The HIV epidemic imposes a 

particular burden on women and 

children, specifically in sub-Saharan 

Africa where women account for 

approximately 57 percent of all people 

living with HIV (Ref. 34). In 2012, there 

were an estimated 260,000 newly 

infected children in LMICs (id.). 

Children with HIV are more likely to 

face gaps in access to HIV treatment. In 

2012, approximately 34 percent of 

children had access to HIV treatment 

versus approximately 64 percent for 

adults (id.). Since PCP is the most 

prevalent in persons infected with HIV 

(Ref. 1) and HIV disproportionately 

impacts women and children, it is 

reasonable to conclude that PCP also 

disproportionately affects these 

populations. 


daltland on DSKBBV9HB2PROD with NOTICES
42898 Federal Register / Vol. 83, No. 165 / Friday, August 24, 2018 / Notices 

PCP has not been designated by the 

World Health Organization (WHO) as a 

neglected tropical disease (Ref. 35). 

C. FDA Determination 

In sum, although PCP 

disproportionately affects poor and 

marginalized populations, it is an 

infectious disease for which there is a 

significant market in developed nations 

for drugs indicated for prevention of 

PCP. Based on the information 

reviewed, FDA has determined that PCP 

does not meet the statutory criteria for 

a tropical disease in section 524 of the 

FD&C Act. 

III. Process for Requesting Additional 

Diseases To Be Added to the List 

FDA’s current determination 

regarding PCP does not preclude 

interested persons from requesting its 

consideration in the future. To facilitate 

the consideration of future additions to 

the list, FDA established a public docket 

(see https://www.regulations.gov, 

Docket No. FDA–2008–N–0567) through 

which interested persons may submit 

requests for additional diseases to be 

added to the list. Such requests should 

be accompanied by information to 

document that the disease meets the 

criteria set forth in section 524(a)(3)(S) 

of the FD&C Act. FDA will periodically 

review these requests, and, when 

appropriate, expand the list. For further 

information, see https://www.fda.gov/ 

AboutFDA/CentersOffices/Officeof

MedicalProductsandTobacco/CDER/ 

ucm534162.htm. 

IV. Paperwork Reduction Act 

This notice reiterates the ‘‘open’’ 

status of the previously established 

public docket through which interested 

persons may submit requests for 

additional diseases to be added to the 

list of tropical diseases that FDA has 

found to meet the criteria in section 

524(a)(3)(S) of the FD&C Act. Such a 

request for information is exempt from 

Office of Management and Budget 

review under 5 CFR 1320.3(h)(4) of the 

Paperwork Reduction Act of 1995 (44 

U.S.C. 3501–3520). Specifically, ‘‘[f]acts 

or opinions submitted in response to 

general solicitations of comments from 

the public, published in the Federal 

Register or other publications, 

regardless of the form or format thereof’’ 

are exempt, ‘‘provided that no person is 

required to supply specific information 

pertaining to the commenter, other than 

that necessary for self-identification, as 

a condition of the Agency’s full 

consideration of the comment.’’ 

V. References 

The following references have been 

placed on display at the Dockets 

Management Staff (see ADDRESSES). 

They may be seen by interested persons 

between 9 a.m. and 4 p.m. Monday 

through Friday and are available 

electronically at https://

www.regulations.gov. (FDA has verified 

the website addresses, but FDA is not 

responsible for any subsequent changes 

to the websites after this document 

publishes in the Federal Register.) 

1. Thomas, C.F., Jr. and A.H. Limper, 

‘‘Pneumocystis Pneumonia,’’ The New 

England Journal of Medicine, 

350(24):2487–2498, June 10, 2004. 

2. Centers for Disease Control and Prevention 

(CDC), ‘‘HIV Surveillance Report, 2015,’’ 

vol. 27, November 2016, available at 

https://www.cdc.gov/hiv/library/reports/ 

hiv-surveillance.html, accessed January 

19, 2017. 

3. United Network for Organ Sharing, 

‘‘Annual Reports,’’ accessed December 

16, 2016, available at https://

www.unos.org/about/annual-report/. 

4. The U.S. Health Resources and Services 

Administration, ‘‘Transplant Activity 

Report: Total Transplants by Year,’’ 

accessed January 19, 2017, available at 

https://bloodcell.transplant.hrsa.gov/ 

research/transplant_data/transplant_

activity_report/index.html. 

5. The American Cancer Society, ‘‘Key 

Statistics for Acute Lymphocytic 

Leukemia,’’ accessed January 19, 2017, 

available at http://www.cancer.org/ 

cancer/leukemia-acutelymphocyticall

inadults/detailedguide/leukemia-acutelymphocytic-key-statistics. 

6. Miller, R.F., L. Huang, and P.D. Walzer, 

‘‘Pneumocystis Pneumonia Associated 

with Human Immunodeficiency Virus,’’ 

Clinics in Chest Medicine, 34(2):229– 

241, June 2013. 

7. Morris, A., J.D. Lundgren, H. Masur, et al., 

‘‘Current Epidemiology of Pneumocystis 

Pneumonia,’’ Emerging Infectious 

Diseases, 10(10):1713–720, October 

2004. 

8. Azoulay, E., A. Bergeron, S. Chevret, N. 

Bele, et al., ‘‘Polymerase Chain Reaction 

for Diagnosing Pneumocystis Pneumonia 

in Non-HIV Immunocompromised 

Patients with Pulmonary Infiltrates,’’ 

Chest, 135(3):655–661, March 2009. 

9. Gamaletsou, M.N., M. DrogariApiranthitou, D.W. Denning, et al., ‘‘An 

Estimate of the Burden of Serious Fungal 

Diseases in Greece,’’ European Journal of 

Clinical Microbiology & Infectious 

Diseases (official publication of the 

European Society of Clinical 

Microbiology), 35(7):1115–1120, July 

2016. 

10. Buchacz, K., R.K. Baker, F.J. Palella, Jr., 

et al., ‘‘AIDS-Defining Opportunistic 

Illnesses in US patients, 1994–2007: A 

Cohort Study,’’ AIDS, 24(10):1549–1559, 

Jun 19, 2010. 

11. Maini, R., K.L. Henderson, E.A. Sheridan, 

et al., ‘‘Increasing Pneumocystis 

Pneumonia, England, UK, 2000–2010,’’ 

Emerging Infectious Diseases, 19(3):386– 

392, March 2013. 

12. Walzer, P.D. and A.G. Smulian, 

‘‘Pneumocystis species,’’ in: Mandell, 

G.L., Bennett, J.E., Dolin, R., eds. 

Mandell, Douglas, and Bennett’s 

Principles and Practice of Infectious 

Disease, 7th ed. PA: Elsevier; 2010, 

3377–90. 

13. CDC, Fungal Diseases, ‘‘Pneumocystis 

Pneumonia,’’ February 21, 2018, 

available at https://www.cdc.gov/fungal/ 

diseases/pneumocystis-pneumonia, 

accessed November 21, 2016. 

14. Kaplan, J.E., H. Masur, K.K. Holmes, et 

al., ‘‘USPHS/IDSA Guidelines for the 

Prevention of Opportunistic Infections in 

Persons Infected with Human 

Immunodeficiency Virus: A Summary,’’ 

USPHS/IDSA Prevention of 

Opportunistic Infections Working Group, 

Clinical Infectious Diseases: An Official 

Publication of the Infectious Diseases 

Society of America, 21(Suppl 1):S12–31, 

August 1995. 

15. Mohar, A., J. Romo, F. Salido, et al., ‘‘The 

Spectrum of Clinical and Pathological 

Manifestations of AIDS in a Consecutive 

Series of Autopsied Patients in Mexico,’’ 

AIDS, 6(5):467–473, May 1992. 

16. Wannamethee, S.G., S. Sirivichayakul, A. 

N. Phillips, et al., ‘‘Clinical and 

Immunological Features of Human 

Immunodeficiency Virus Infection in 

Patients from Bangkok, Thailand,’’ 

International Journal of Epidemiology, 

27(2):289–295, April 1998. 

17. Weinberg, A. and M.I. Duarte, 

‘‘Respiratory Complications in Brazilian 

Patients Infected with Human 

Immunodeficiency Virus,’’ Revista do 

Instituto de Medicina Tropical de Sao 

Paulo, 35(2):129–139, March–April 1993. 

18. Lagrou, K., J. Maertens, E. Van Even, et 

al., ‘‘Burden of Serious Fungal Infections 

in Belgium,’’ Mycoses, 58(Suppl 5):1–5, 

October 2015. 

19. Faini, D., W. Maokola, W., H. Furrer, et 

al., ‘‘Burden of Serious Fungal Infections 

in Tanzania,’’ Mycoses, 58(Suppl 5):70– 

79, October 2015. 

20. Worodria, W., J.L. Davis, A. Cattamanchi, 

et al., ‘‘Bronchoscopy is Useful for 

Diagnosing Smear-Negative Tuberculosis 

in HIV-Infected Patients,’’ The European 

Respiratory Journal, 36(2):446–448, 

August 2010. 

21. Parkes-Ratanshi, R., B. Achan, R. 

Kwizera, et al., ‘‘Cryptococcal Disease 

and the Burden of Other Fungal Diseases 

in Uganda; Where are the Knowledge 

Gaps and How Can We Fill Them?’’ 

Mycoses, 58(Suppl 5):85–93, October 

2015. 

22. Beardsley, J., D.W. Denning, N.V. Chau, 

et al., ‘‘Estimating the Burden of Fungal 

Disease in Vietnam,’’ Mycoses, 58(Suppl 

5):101–106, October 2015. 

23. Badiane, A.S., D. Ndiaye, D.W. Denning, 

‘‘Burden of Fungal Infections in 

Senegal,’’ Mycoses, 58(Suppl 5):63–69, 

October 2015. 

24. Khwakhali, U.S. and D.W. Denning, 

‘‘Burden of Serious Fungal Infections in 

Nepal,’’ Mycoses, 58(Suppl 5):45–50, 

October 2015. 


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25. Osmanov, A. and D.W. Denning, ‘‘Burden 

of Serious Fungal Infections in Ukraine,’’ 

Mycoses, 58(Suppl 5): 94–100, October 

2015. 

26. Morrow, B.M., N.Y. Hsaio, M. Zampoli, 

et al., ‘‘Pneumocystis Pneumonia in 

South African Children with and 

Without Human Immunodeficiency 

Virus Infection in the Era of Highly 

Active Antiretroviral Therapy,’’ The 

Pediatric Infectious Disease Journal, 

29(6):535–539, June 2010. 

27. Stansell, J.D., D.H. Osmond, E. 

Charlebois, E., et al., ‘‘Predictors of 

Pneumocystis carinii Pneumonia in HIVInfected Persons. Pulmonary 

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and Critical Care Medicine, 155(1):60– 

66, January 1997. 

28. Wasserman, S., M.E. Engel, M. 

Mendelson, ‘‘Burden of Pneumocystis 

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Reviews, 2:112, December 12, 2013. 

29. Fisk, D.T., S. Meshnick, S., and P.H. 

Kazanjian, ‘‘Pneumocystis carinii 

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World Who Have Acquired 

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Society of America, 36(1):70–78, January 

1, 2003. 

30. de Boer, M.G., J.W. de Fijter, F.P. Kroon, 

‘‘Outbreaks and Clustering of 

Pneumocystis Pneumonia in Kidney 

Transplant Recipients: A Systematic 

Review,’’ Medical Mycology, 49(7):673– 

680, October 2011. 

31. Sonego, M., M.C. Pellegrin, G. Becker, et 

al., ‘‘Risk Factors for Mortality from 

Acute Lower Respiratory Infections 

(ALRI) in Children under Five Years of 

Age in Low and Middle-Income 

Countries: A Systematic Review and 

Meta-Analysis of Observational Studies,’’ 

PLOS One, 10(1):e0116380, 2015. 

32. Morris, A., J.D. Lundgren, H. Masur, et 

al., ‘‘Current Epidemiology of 

Pneumocystis Pneumonia,’’ Emerging 

Infectious Diseases, 10(10):1713–1720, 

October 2004. 

33. Avino, L.J., S.M. Naylor, A.M. Roecker, 

‘‘Pneumocystis jirovecii Pneumonia in 

the Non-HIV-Infected Population,’’ The 

Annals of Pharmacotherapy, 50(8):673– 

679, August 2016. 

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AIDS (UNAIDS), ‘‘Global Report: 

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Epidemic 2013,’’ accessed December 9, 

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diseases/en/. 

Dated: August 21, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–18313 Filed 8–23–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket Nos. FDA–2018–P–0964 and FDA– 

2018–P–0967] 

Determination That PLASMA–LYTE M 

AND DEXTROSE 5% and PLASMA 

LYTE 148 AND DEXTROSE 5% Were 

Not Withdrawn From Sale for Reasons 

of Safety or Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) has 

determined that PLASMA–LYTE M 

AND DEXTROSE 5% (calcium chloride, 

37 milligrams (mg)/100 milliliters (mL); 

dextrose, 5 grams (g)/100 mL; 

magnesium chloride, 30 mg/100 mL; 

potassium chloride, 119 mg/100 mL; 

sodium acetate, 161 mg/100 mL; sodium 

chloride, 94 mg/100 mL; sodium lactate, 

138 mg/100 mL) and PLASMA LYTE 

148 AND DEXTROSE 

5% (dextrose, 5 g/100 mL; magnesium 

chloride, 30 mg/100 mL; potassium 

chloride, 37 mg/100 mL; sodium 

acetate, 368 mg/100 mL; sodium 

chloride, 526 mg/100 mL; sodium 

gluconate, 502 mg/100 mL) were not 

withdrawn from sale for reasons of 

safety or effectiveness. This 

determination means that FDA will not 

begin procedures to withdraw approval 

of abbreviated new drug applications 

(ANDAs) that refer to these drug 

products, and it will allow FDA to 

continue to approve ANDAs that refer to 

these products as long as they meet 

relevant legal and regulatory 

requirements. 

FOR FURTHER INFORMATION CONTACT: 

Heather A. Dorsey, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6219, 

Silver Spring, MD 20993–0002, 301– 

796–3601. 

SUPPLEMENTARY INFORMATION: In 1984, 

Congress enacted the Drug Price 

Competition and Patent Term 

Restoration Act of 1984 (Pub. L. 98–417) 

(the 1984 amendments), which 

authorized the approval of duplicate 

versions of drug products under an 

ANDA procedure. ANDA applicants 

must, with certain exceptions, show that 

the drug for which they are seeking 

approval contains the same active 

ingredient in the same strength and 

dosage form as the ‘‘listed drug,’’ which 

is a version of the drug that was 

previously approved. ANDA applicants 

do not have to repeat the extensive 

clinical testing otherwise necessary to 

gain approval of a new drug application 

(NDA). 

The 1984 amendments include what 

is now section 505(j)(7) of the Federal 

Food, Drug, and Cosmetic Act (21 U.S.C. 

355(j)(7)), which requires FDA to 

publish a list of all approved drugs. 

FDA publishes this list as part of the 

‘‘Approved Drug Products With 

Therapeutic Equivalence Evaluations,’’ 

which is known generally as the 

‘‘Orange Book.’’ Under FDA regulations, 

drugs are removed from the list if the 

Agency withdraws or suspends 

approval of the drug’s NDA or ANDA 

for reasons of safety or effectiveness or 

if FDA determines that the listed drug 

was withdrawn from sale for reasons of 

safety or effectiveness (21 CFR 314.162). 

A person may petition the Agency to 

determine, or the Agency may 

determine on its own initiative, whether 

a listed drug was withdrawn from sale 

for reasons of safety or effectiveness. 

This determination may be made at any 

time after the drug has been withdrawn 

from sale, but must be made prior to 

approving an ANDA that refers to the 

listed drug (§ 314.161 (21 CFR 314.161)). 

FDA may not approve an ANDA that 

does not refer to a listed drug. 

PLASMA–LYTE M AND DEXTROSE 

5% (calcium chloride, 37 mg/100 mL; 

dextrose, 5 g/100 mL; magnesium 

chloride, 30 mg/100 mL; potassium 

chloride, 119 mg/100 mL; sodium 

acetate, 161 mg/100 mL; sodium 

chloride, 94 mg/100 mL; sodium lactate, 

138 mg/100 mL) is the subject of NDA 

017390, held by Baxter Healthcare 

Corp., and initially approved on 

February 1, 1979. PLASMA LYTE 148 

AND DEXTROSE 5% (dextrose, 5 g/100 

mL; magnesium chloride, 30 mg/100 

mL; potassium chloride, 37 mg/100 mL; 

sodium acetate, 368 mg/100 mL; sodium 

chloride, 526 mg/100 mL; sodium 

gluconate, 502 mg/100 mL) is the 

subject of NDA 017451, held by Baxter 

Healthcare Corp., and initially approved 

on February 2, 1979. PLASMA LYTE M 

AND DEXTROSE 5% is indicated as a 

source of water, electrolytes, and 

calories or as an alkalinizing agent. 

PLASMA LYTE 148 AND DEXTROSE 

5% is indicated as a source of water, 

electrolytes, and calories, or as an 

alkalinizing agent. 

PLASMA–LYTE M AND DEXTROSE 

5% (calcium chloride, 37 mg/100 mL; 

dextrose, 5 g/100 mL; magnesium 

chloride, 30 mg/100 mL; potassium 

chloride, 119 mg/100 mL; sodium 

acetate, 161 mg/100 mL; sodium 

chloride, 94 mg/100 mL; sodium lactate, 

138 mg/100 mL) and PLASMA LYTE 

148 AND DEXTROSE 


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