83 FR 42896 - Notice of Decision Not To Designate Pneumocystis Pneumonia as a Tropical Disease
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 165 (August 24, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 165 (August 24, 2018)
| Page Range | 42896-42899 | |
| FR Document | 2018-18313 |
[Federal Register Volume 83, Number 165 (Friday, August 24, 2018)] [Notices] [Pages 42896-42899] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-18313] ----------------------------------------------------------------------- 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, [email protected]; 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, [email protected]. 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/designating-additions-to-the-current-list-of-tropical-diseases-in-the-federal-food-drug-and-cosmetic). Additions to the statutory list of tropical diseases published in the Federal Register can be accessed at https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/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 [[Page 42897]] https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/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 post- transplantation 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/ [micro]L or a history of oral candidiasis (Ref. 14). As indicated above, the prevalence of stage-3 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 HIV-infected 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 sub-Saharan 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. [[Page 42898]] 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/OfficeofMedicalProductsandTobacco/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-acutelymphocyticallinadults/detailedguide/leukemia-acute-lymphocytic-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. Drogari-Apiranthitou, 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[hyphen]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. [[Page 42899]] 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 HIV-Infected Persons. Pulmonary Complications of HIV Infection Study Group,'' American Journal of Respiratory and Critical Care Medicine, 155(1):60-66, January 1997. 28. Wasserman, S., M.E. Engel, M. Mendelson, ``Burden of Pneumocystis Pneumonia in HIV-Infected Adults in Sub-Saharan Africa: Protocol for a Systematic Review,'' Systematic Reviews, 2:112, December 12, 2013. 29. Fisk, D.T., S. Meshnick, S., and P.H. Kazanjian, ``Pneumocystis carinii Pneumonia in Patients in the Developing World Who Have Acquired Immunodeficiency Syndrome,'' Clinical Infectious Diseases: An Official Publication of the Infectious Diseases 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. 34. Joint United Nations Programme on HIV/AIDS (UNAIDS), ``Global Report: UNAIDS Report on the Global AIDS Epidemic 2013,'' accessed December 9, 2016, available at http://files.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf. 35. WHO, ``Neglected Tropical Diseases,'' accessed December 9, 2016, available at http://www.who.int/neglected_diseases/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
![42896 Federal Register / Vol. 83, No. 165 / Friday, August 24, 2018 / Notices
ANNUAL BURDEN ESTIMATES—Continued
Number of Average
Number of Total burden
Instrument responses per burden hours
respondents hours
respondent per response
Letter of Designation ....................................................................................... 25,000 1 0.5 12,500
Estimated Total Annual Burden per populations and whether there is ‘‘no drugs, including biologics, for
Respondent: 207,500. significant market’’ for drugs that prevention and treatment of certain
Additional Information: Copies of the prevent or treat PCP in developed diseases that, in the aggregate, affect
proposed collection may be obtained by countries. The Agency has determined millions of people throughout the
writing to the Administration for that PCP does not meet the statutory world. Further information about the
Children and Families, Office of criteria for designation as a tropical tropical disease PRV program can be
Planning, Research and Evaluation, 330 disease and declines to designate it as found in guidance for industry
C Street SW, Washington, DC 20201. such. ‘‘Tropical Disease Priority Review
Attention Reports Clearance Officer. All DATES: August 24, 2018. Vouchers’’ (81 FR 69537, October 6,
requests should be identified by the title ADDRESSES: Submit electronic 2016, available at https://
of the information collection. Email comments on additional diseases www.federalregister.gov/documents/
address: infocollection@acf.hhs.gov. suggested for designation to https:// 2015/08/20/2015-20554/designating-
OMB Comment: OMB is required to www.regulations.gov. Submit written additions-to-the-current-list-of-tropical-
make a decision concerning the comments on additional diseases diseases-in-the-federal-food-drug-and-
collection of information between 30 suggested for designation to the Dockets cosmetic). Additions to the statutory list
and 60 days after publication of this Management Staff (HFA–305), Food and of tropical diseases published in the
document in the Federal Register. Drug Administration, 5630 Fishers Federal Register can be accessed at
Therefore, a comment is best assured of Lane, Rm. 1061, Rockville, MD 20852. https://www.fda.gov/AboutFDA/Centers
having its full effect if OMB receives it All comments should be identified with Offices/OfficeofMedicalProducts
within 30 days of publication. Written the docket number found in brackets in andTobacco/CDER/ucm534162.htm.
comments and recommendations for the the heading of this document. In August 2015, FDA published a
proposed information collection should final order (80 FR 50559, August 20,
FOR FURTHER INFORMATION CONTACT:
be sent directly to the following: Office 2015) (final order) designating Chagas
Katherine Schumann, Center for Drug
of Management and Budget, Paperwork disease and neurocysticercosis as
Evaluation and Research, Food and
Reduction Project, Email: OIRA_ tropical diseases. That final order also
Drug Administration, 10903 New
SUBMISSION@OMB.EOP.GOV, Attn: sets forth FDA’s interpretation of the
Hampshire Ave., Bldg. 22, Rm. 6242,
Desk Officer for the Administration for statutory criteria for tropical disease
Silver Spring, MD 20993–0002, 301–
Children and Families. designation and expands the list of
796–1300, Katherine.Schumann@
Robert A. Sargis, fda.hhs.gov; or Office of tropical diseases under section
Communication, Outreach and 524(a)(3)(R) of the FD&C Act, which
Reports Clearance Officer.
Development (OCOD), Center for authorizes the FDA to designate by
[FR Doc. 2018–18351 Filed 8–23–18; 8:45 am]
Biologics Evaluation and Research, order ‘‘[a]ny other infectious disease for
BILLING CODE 4184–01–P
Food and Drug Administration, 10903 which there is no significant market in
New Hampshire Ave., Silver Spring, MD developed nations and that
20993–0002, 800–835–4709 or 240– disproportionately affects poor and
DEPARTMENT OF HEALTH AND
402–8010, ocod@fda.hhs.gov. marginalized populations’’ as a tropical
HUMAN SERVICES
disease.
SUPPLEMENTARY INFORMATION:
Food and Drug Administration FDA has applied its August 2015
Table of Contents criteria as set forth in the final order to
[Docket No. FDA–2008–N–0567] analyze whether PCP meets the
I. Background: Priority Review Voucher
Program statutory criteria for addition to the
Notice of Decision Not To Designate
II. Decision Not To Designate Pneumocystis tropical disease list. As discussed
Pneumocystis Pneumonia as a
Pneumonia below, the Agency has determined that
Tropical Disease A. Significant Market in Developed PCP does not meet the statutory criteria
AGENCY: Food and Drug Administration, Nations for designation as a ‘‘tropical disease’’
HHS. B. Disproportionately Affects Poor and and thus will not add it to the list of
Marginalized Populations tropical diseases whose applications
ACTION: Notice. C. FDA Determination
III. Process for Requesting Additional may be eligible for a priority review
SUMMARY: The Food and Drug Diseases To Be Added to the List voucher.
Administration (FDA or Agency), in IV. Paperwork Reduction Act
response to suggestions submitted to II. Decision Not To Designate
V. References
Docket No. FDA–2008–N–0567, has Pneumocystis Pneumonia
analyzed whether Pneumocystis I. Background: Priority Review FDA has considered all diseases
daltland on DSKBBV9HB2PROD with NOTICES
pneumonia (PCP) meets the statutory Voucher Program submitted to the public docket (FDA–
criteria for designation as a tropical Section 524 of the FD&C Act (21 2008–N–0567) between August 20,
disease for the purposes of obtaining a U.S.C. 360n), which was added by 2015, and June 20, 2018, as potential
priority review voucher (PRV) under the section 1102 of the Food and Drug additions to the list of tropical diseases
Federal Food, Drug, and Cosmetic Act Administration Amendments Act of under section 524 of the FD&C Act,
(FD&C Act), namely whether it 2007 (FDAAA), uses a PRV incentive to under the docket review process
primarily affects poor and marginalized encourage the development of new explained on the Agency’s website (see
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![42898 Federal Register / Vol. 83, No. 165 / Friday, August 24, 2018 / Notices
PCP has not been designated by the V. References Emerging Infectious Diseases, 19(3):386–
World Health Organization (WHO) as a 392, March 2013.
The following references have been 12. Walzer, P.D. and A.G. Smulian,
neglected tropical disease (Ref. 35). placed on display at the Dockets ‘‘Pneumocystis species,’’ in: Mandell,
C. FDA Determination Management Staff (see ADDRESSES). G.L., Bennett, J.E., Dolin, R., eds.
They may be seen by interested persons Mandell, Douglas, and Bennett’s
In sum, although PCP between 9 a.m. and 4 p.m. Monday Principles and Practice of Infectious
disproportionately affects poor and through Friday and are available Disease, 7th ed. PA: Elsevier; 2010,
electronically at https:// 3377–90.
marginalized populations, it is an
13. CDC, Fungal Diseases, ‘‘Pneumocystis
infectious disease for which there is a www.regulations.gov. (FDA has verified
Pneumonia,’’ February 21, 2018,
significant market in developed nations the website addresses, but FDA is not available at https://www.cdc.gov/fungal/
for drugs indicated for prevention of responsible for any subsequent changes diseases/pneumocystis-pneumonia,
PCP. Based on the information to the websites after this document accessed November 21, 2016.
reviewed, FDA has determined that PCP publishes in the Federal Register.) 14. Kaplan, J.E., H. Masur, K.K. Holmes, et
does not meet the statutory criteria for 1. Thomas, C.F., Jr. and A.H. Limper, al., ‘‘USPHS/IDSA Guidelines for the
‘‘Pneumocystis Pneumonia,’’ The New Prevention of Opportunistic Infections in
a tropical disease in section 524 of the Persons Infected with Human
FD&C Act. England Journal of Medicine,
350(24):2487–2498, June 10, 2004. Immunodeficiency Virus: A Summary,’’
USPHS/IDSA Prevention of
III. Process for Requesting Additional 2. Centers for Disease Control and Prevention
Opportunistic Infections Working Group,
Diseases To Be Added to the List (CDC), ‘‘HIV Surveillance Report, 2015,’’
vol. 27, November 2016, available at Clinical Infectious Diseases: An Official
https://www.cdc.gov/hiv/library/reports/ Publication of the Infectious Diseases
FDA’s current determination Society of America, 21(Suppl 1):S12–31,
regarding PCP does not preclude hiv-surveillance.html, accessed January
19, 2017. August 1995.
interested persons from requesting its 15. Mohar, A., J. Romo, F. Salido, et al., ‘‘The
3. United Network for Organ Sharing,
consideration in the future. To facilitate ‘‘Annual Reports,’’ accessed December Spectrum of Clinical and Pathological
the consideration of future additions to 16, 2016, available at https:// Manifestations of AIDS in a Consecutive
the list, FDA established a public docket www.unos.org/about/annual-report/. Series of Autopsied Patients in Mexico,’’
(see https://www.regulations.gov, 4. The U.S. Health Resources and Services AIDS, 6(5):467–473, May 1992.
Administration, ‘‘Transplant Activity 16. Wannamethee, S.G., S. Sirivichayakul, A.
Docket No. FDA–2008–N–0567) through N. Phillips, et al., ‘‘Clinical and
which interested persons may submit Report: Total Transplants by Year,’’
accessed January 19, 2017, available at Immunological Features of Human
requests for additional diseases to be https://bloodcell.transplant.hrsa.gov/ Immunodeficiency Virus Infection in
added to the list. Such requests should research/transplant_data/transplant_ Patients from Bangkok, Thailand,’’
be accompanied by information to activity_report/index.html. International Journal of Epidemiology,
document that the disease meets the 5. The American Cancer Society, ‘‘Key 27(2):289–295, April 1998.
criteria set forth in section 524(a)(3)(S) Statistics for Acute Lymphocytic 17. Weinberg, A. and M.I. Duarte,
Leukemia,’’ accessed January 19, 2017, ‘‘Respiratory Complications in Brazilian
of the FD&C Act. FDA will periodically
available at http://www.cancer.org/ Patients Infected with Human
review these requests, and, when Immunodeficiency Virus,’’ Revista do
cancer/leukemia-acutelymphocyticall
appropriate, expand the list. For further inadults/detailedguide/leukemia-acute- Instituto de Medicina Tropical de Sao
information, see https://www.fda.gov/ lymphocytic-key-statistics. Paulo, 35(2):129–139, March–April 1993.
AboutFDA/CentersOffices/Officeof 6. Miller, R.F., L. Huang, and P.D. Walzer, 18. Lagrou, K., J. Maertens, E. Van Even, et
MedicalProductsandTobacco/CDER/ ‘‘Pneumocystis Pneumonia Associated al., ‘‘Burden of Serious Fungal Infections
ucm534162.htm. with Human Immunodeficiency Virus,’’ in Belgium,’’ Mycoses, 58(Suppl 5):1–5,
Clinics in Chest Medicine, 34(2):229– October 2015.
IV. Paperwork Reduction Act 241, June 2013. 19. Faini, D., W. Maokola, W., H. Furrer, et
7. Morris, A., J.D. Lundgren, H. Masur, et al., al., ‘‘Burden of Serious Fungal Infections
This notice reiterates the ‘‘open’’ ‘‘Current Epidemiology of Pneumocystis in Tanzania,’’ Mycoses, 58(Suppl 5):70–
status of the previously established Pneumonia,’’ Emerging Infectious 79, October 2015.
public docket through which interested Diseases, 10(10):1713–720, October 20. Worodria, W., J.L. Davis, A. Cattamanchi,
persons may submit requests for 2004. et al., ‘‘Bronchoscopy is Useful for
8. Azoulay, E., A. Bergeron, S. Chevret, N. Diagnosing Smear-Negative Tuberculosis
additional diseases to be added to the
Bele, et al., ‘‘Polymerase Chain Reaction in HIV-Infected Patients,’’ The European
list of tropical diseases that FDA has for Diagnosing Pneumocystis Pneumonia Respiratory Journal, 36(2):446–448,
found to meet the criteria in section in Non-HIV Immunocompromised August 2010.
524(a)(3)(S) of the FD&C Act. Such a Patients with Pulmonary Infiltrates,’’ 21. Parkes-Ratanshi, R., B. Achan, R.
request for information is exempt from Chest, 135(3):655–661, March 2009. Kwizera, et al., ‘‘Cryptococcal Disease
Office of Management and Budget 9. Gamaletsou, M.N., M. Drogari- and the Burden of Other Fungal Diseases
review under 5 CFR 1320.3(h)(4) of the Apiranthitou, D.W. Denning, et al., ‘‘An in Uganda; Where are the Knowledge
Paperwork Reduction Act of 1995 (44 Estimate of the Burden of Serious Fungal Gaps and How Can We Fill Them?’’
Diseases in Greece,’’ European Journal of Mycoses, 58(Suppl 5):85–93, October
U.S.C. 3501–3520). Specifically, ‘‘[f]acts Clinical Microbiology & Infectious 2015.
or opinions submitted in response to Diseases (official publication of the 22. Beardsley, J., D.W. Denning, N.V. Chau,
general solicitations of comments from European Society of Clinical et al., ‘‘Estimating the Burden of Fungal
the public, published in the Federal Microbiology), 35(7):1115–1120, July Disease in Vietnam,’’ Mycoses, 58(Suppl
Register or other publications, 2016. 5):101–106, October 2015.
daltland on DSKBBV9HB2PROD with NOTICES
regardless of the form or format thereof’’ 10. Buchacz, K., R.K. Baker, F.J. Palella, Jr., 23. Badiane, A.S., D. Ndiaye, D.W. Denning,
are exempt, ‘‘provided that no person is et al., ‘‘AIDS-Defining Opportunistic ‘‘Burden of Fungal Infections in
Illnesses in US patients, 1994–2007: A Senegal,’’ Mycoses, 58(Suppl 5):63–69,
required to supply specific information
Cohort Study,’’ AIDS, 24(10):1549–1559, October 2015.
pertaining to the commenter, other than Jun 19, 2010. 24. Khwakhali, U.S. and D.W. Denning,
that necessary for self-identification, as 11. Maini, R., K.L. Henderson, E.A. Sheridan, ‘‘Burden of Serious Fungal Infections in
a condition of the Agency’s full et al., ‘‘Increasing Pneumocystis Nepal,’’ Mycoses, 58(Suppl 5):45–50,
consideration of the comment.’’ Pneumonia, England, UK, 2000–2010,’’ October 2015.
VerDate Sep<11>2014 19:17 Aug 23, 2018 Jkt 244001 PO 00000 Frm 00040 Fmt 4703 Sfmt 4703 E:\FR\FM\24AUN1.SGM 24AUN1](https://thefederalregister.org/doc/83_FR_43061/page/3.svg)
![Federal Register / Vol. 83, No. 165 / Friday, August 24, 2018 / Notices 42899
25. Osmanov, A. and D.W. Denning, ‘‘Burden DEPARTMENT OF HEALTH AND do not have to repeat the extensive
of Serious Fungal Infections in Ukraine,’’ HUMAN SERVICES clinical testing otherwise necessary to
Mycoses, 58(Suppl 5): 94–100, October gain approval of a new drug application
2015. Food and Drug Administration (NDA).
26. Morrow, B.M., N.Y. Hsaio, M. Zampoli,
et al., ‘‘Pneumocystis Pneumonia in
The 1984 amendments include what
[Docket Nos. FDA–2018–P–0964 and FDA–
South African Children with and 2018–P–0967] is now section 505(j)(7) of the Federal
Without Human Immunodeficiency Food, Drug, and Cosmetic Act (21 U.S.C.
Virus Infection in the Era of Highly Determination That PLASMA–LYTE M 355(j)(7)), which requires FDA to
Active Antiretroviral Therapy,’’ The AND DEXTROSE 5% and PLASMA publish a list of all approved drugs.
Pediatric Infectious Disease Journal, LYTE 148 AND DEXTROSE 5% Were FDA publishes this list as part of the
29(6):535–539, June 2010. ‘‘Approved Drug Products With
27. Stansell, J.D., D.H. Osmond, E. Not Withdrawn From Sale for Reasons
of Safety or Effectiveness Therapeutic Equivalence Evaluations,’’
Charlebois, E., et al., ‘‘Predictors of
Pneumocystis carinii Pneumonia in HIV-
which is known generally as the
Infected Persons. Pulmonary
AGENCY: Food and Drug Administration, ‘‘Orange Book.’’ Under FDA regulations,
Complications of HIV Infection Study HHS. drugs are removed from the list if the
Group,’’ American Journal of Respiratory ACTION: Notice. Agency withdraws or suspends
and Critical Care Medicine, 155(1):60– approval of the drug’s NDA or ANDA
66, January 1997. SUMMARY: The Food and Drug for reasons of safety or effectiveness or
28. Wasserman, S., M.E. Engel, M. Administration (FDA or Agency) has if FDA determines that the listed drug
Mendelson, ‘‘Burden of Pneumocystis determined that PLASMA–LYTE M was withdrawn from sale for reasons of
Pneumonia in HIV-Infected Adults in AND DEXTROSE 5% (calcium chloride,
Sub-Saharan Africa: Protocol for a
safety or effectiveness (21 CFR 314.162).
Systematic Review,’’ Systematic
37 milligrams (mg)/100 milliliters (mL); A person may petition the Agency to
Reviews, 2:112, December 12, 2013. dextrose, 5 grams (g)/100 mL; determine, or the Agency may
29. Fisk, D.T., S. Meshnick, S., and P.H. magnesium chloride, 30 mg/100 mL; determine on its own initiative, whether
Kazanjian, ‘‘Pneumocystis carinii potassium chloride, 119 mg/100 mL; a listed drug was withdrawn from sale
Pneumonia in Patients in the Developing sodium acetate, 161 mg/100 mL; sodium for reasons of safety or effectiveness.
World Who Have Acquired chloride, 94 mg/100 mL; sodium lactate, This determination may be made at any
Immunodeficiency Syndrome,’’ Clinical 138 mg/100 mL) and PLASMA LYTE time after the drug has been withdrawn
Infectious Diseases: An Official from sale, but must be made prior to
148 AND DEXTROSE
Publication of the Infectious Diseases
Society of America, 36(1):70–78, January 5% (dextrose, 5 g/100 mL; magnesium approving an ANDA that refers to the
1, 2003. chloride, 30 mg/100 mL; potassium listed drug (§ 314.161 (21 CFR 314.161)).
30. de Boer, M.G., J.W. de Fijter, F.P. Kroon, chloride, 37 mg/100 mL; sodium FDA may not approve an ANDA that
‘‘Outbreaks and Clustering of acetate, 368 mg/100 mL; sodium does not refer to a listed drug.
Pneumocystis Pneumonia in Kidney chloride, 526 mg/100 mL; sodium PLASMA–LYTE M AND DEXTROSE
Transplant Recipients: A Systematic gluconate, 502 mg/100 mL) were not 5% (calcium chloride, 37 mg/100 mL;
Review,’’ Medical Mycology, 49(7):673– withdrawn from sale for reasons of dextrose, 5 g/100 mL; magnesium
680, October 2011. chloride, 30 mg/100 mL; potassium
31. Sonego, M., M.C. Pellegrin, G. Becker, et safety or effectiveness. This
al., ‘‘Risk Factors for Mortality from determination means that FDA will not chloride, 119 mg/100 mL; sodium
Acute Lower Respiratory Infections begin procedures to withdraw approval acetate, 161 mg/100 mL; sodium
(ALRI) in Children under Five Years of of abbreviated new drug applications chloride, 94 mg/100 mL; sodium lactate,
Age in Low and Middle-Income (ANDAs) that refer to these drug 138 mg/100 mL) is the subject of NDA
Countries: A Systematic Review and products, and it will allow FDA to 017390, held by Baxter Healthcare
Meta-Analysis of Observational Studies,’’ continue to approve ANDAs that refer to Corp., and initially approved on
PLOS One, 10(1):e0116380, 2015. February 1, 1979. PLASMA LYTE 148
32. Morris, A., J.D. Lundgren, H. Masur, et
these products as long as they meet
relevant legal and regulatory AND DEXTROSE 5% (dextrose, 5 g/100
al., ‘‘Current Epidemiology of
Pneumocystis Pneumonia,’’ Emerging requirements. mL; magnesium chloride, 30 mg/100
Infectious Diseases, 10(10):1713–1720, mL; potassium chloride, 37 mg/100 mL;
FOR FURTHER INFORMATION CONTACT: sodium acetate, 368 mg/100 mL; sodium
October 2004.
33. Avino, L.J., S.M. Naylor, A.M. Roecker,
Heather A. Dorsey, Center for Drug chloride, 526 mg/100 mL; sodium
‘‘Pneumocystis jirovecii Pneumonia in Evaluation and Research, Food and gluconate, 502 mg/100 mL) is the
the Non-HIV-Infected Population,’’ The Drug Administration, 10903 New subject of NDA 017451, held by Baxter
Annals of Pharmacotherapy, 50(8):673– Hampshire Ave., Bldg. 51, Rm. 6219, Healthcare Corp., and initially approved
679, August 2016. Silver Spring, MD 20993–0002, 301– on February 2, 1979. PLASMA LYTE M
34. Joint United Nations Programme on HIV/ 796–3601.
AIDS (UNAIDS), ‘‘Global Report:
AND DEXTROSE 5% is indicated as a
SUPPLEMENTARY INFORMATION: In 1984, source of water, electrolytes, and
UNAIDS Report on the Global AIDS
Epidemic 2013,’’ accessed December 9, Congress enacted the Drug Price calories or as an alkalinizing agent.
2016, available at http://files.unaids.org/ Competition and Patent Term PLASMA LYTE 148 AND DEXTROSE
en/media/unaids/contentassets/ Restoration Act of 1984 (Pub. L. 98–417) 5% is indicated as a source of water,
documents/epidemiology/2013/gr2013/ (the 1984 amendments), which electrolytes, and calories, or as an
UNAIDS_Global_Report_2013_en.pdf. authorized the approval of duplicate alkalinizing agent.
35. WHO, ‘‘Neglected Tropical Diseases,’’ versions of drug products under an PLASMA–LYTE M AND DEXTROSE
accessed December 9, 2016, available at
ANDA procedure. ANDA applicants 5% (calcium chloride, 37 mg/100 mL;
daltland on DSKBBV9HB2PROD with NOTICES
http://www.who.int/neglected_diseases/
diseases/en/. must, with certain exceptions, show that dextrose, 5 g/100 mL; magnesium
the drug for which they are seeking chloride, 30 mg/100 mL; potassium
Dated: August 21, 2018. approval contains the same active chloride, 119 mg/100 mL; sodium
Leslie Kux, ingredient in the same strength and acetate, 161 mg/100 mL; sodium
Associate Commissioner for Policy. dosage form as the ‘‘listed drug,’’ which chloride, 94 mg/100 mL; sodium lactate,
[FR Doc. 2018–18313 Filed 8–23–18; 8:45 am] is a version of the drug that was 138 mg/100 mL) and PLASMA LYTE
BILLING CODE 4164–01–P previously approved. ANDA applicants 148 AND DEXTROSE
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Document Created: 2018-08-24 04:13:28
Document Modified: 2018-08-24 04:13:28
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| Dates | August 24, 2018. | |
| 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, [email protected]; 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, [email protected] | |
| FR Citation | 83 FR 42896 |
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