Designating Additions to the Current List of Tropical Diseases in the Federal Food, Drug, and Cosmetic Act, 42883-42887 [2020-15252]

Download as PDF Federal Register / Vol. 85, No. 136 / Wednesday, July 15, 2020 / Notices interest to the IRS product manufacturers who submitted timely exceptions, to determine whether the companies remained interested in pursuing their appeals of the ALJ’s Initial Decision. FDA informed the companies that, if they did not respond and affirm their desire to pursue their appeals by January 8, 2018, the Office of the Commissioner would conclude that the companies no longer wish to pursue the appeal of the ALJ’s Initial Decision and will proceed as if the appeals have been withdrawn. The Office of the Commissioner did not receive a response from any of the companies by the given date; therefore, the Commissioner now deems the exceptions withdrawn. II. Conclusion and Order khammond on DSKJM1Z7X2PROD with NOTICES Given that the exceptions have been deemed withdrawn, this proceeding is now in the same procedural posture as if no exceptions had ever been filed. When parties do not file exceptions to the ALJ’s Initial Decision, and the Commissioner does not file a notice of review, the ALJ’s Initial Decision becomes the final decision of the Commissioner (see 21 CFR 12.120(e)). FDA will publish a notice in the Federal Register when an initial decision becomes the final decision of the Commissioner without appeal to or review by the Commissioner (see 21 CFR 12.120(f)). Pursuant to the findings in the ALJ’s Initial Decision, under section 505(e) of the FD&C Act (21 U.S.C. 355(e)), there is a lack of substantial evidence that Vasodilan will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its labeling for: (1) SDAT or multiple infarct dementia and (2) peripheral vascular disease. Distribution of products subject to the Initial Decision in interstate commerce without an approved application is prohibited and subject to regulatory action (see, e.g., sections 505(a) and 301(d) of the FD&C Act (21 U.S.C. 355(a) and 331(d)). The full text of the ALJ’s Initial Decision may be seen at Dockets Management Staff (see ADDRESSES). Dated: July 9, 2020. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2020–15248 Filed 7–14–20; 8:45 am] BILLING CODE 4164–01–P VerDate Sep<11>2014 17:59 Jul 14, 2020 Jkt 250001 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2008–N–0567] Designating Additions to the Current List of Tropical Diseases in the Federal Food, Drug, and Cosmetic Act AGENCY: Food and Drug Administration, HHS. ACTION: Final order. The Federal Food, Drug, and Cosmetic Act (FD&C Act) authorizes the Food and Drug Administration (FDA or Agency) to award priority review vouchers (PRVs) to tropical disease product applicants when the applications meet certain criteria. The FD&C Act lists the diseases that are considered tropical diseases for purposes of obtaining PRVs and provides for Agency expansion of that list to include other diseases that satisfy the definition of ‘‘tropical diseases’’ eligible for PRVs as set forth in the FD&C Act. The Agency has determined that two foodborne trematode infections, opisthorchiasis and paragonimiasis, satisfy this definition, and is therefore adding them to the list of designated tropical diseases whose product applications may result in the award of PRVs. Sponsors submitting certain drug or biological product applications for the prevention or treatment of opisthorchiasis or paragonimiasis infections may be eligible to receive a PRV if such applications are approved by FDA. DATES: This order is issued on July 15, 2020. 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 Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993–0002, 240–402–7911. SUMMARY: PO 00000 Frm 00065 Fmt 4703 Sfmt 4703 42883 SUPPLEMENTARY INFORMATION: Table of Contents I. Background: Priority Review Voucher Program II. Diseases Being Designated A. Opisthorchiasis B. Paragonimiasis 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 (Pub. L. 110–85), uses a PRV incentive to encourage the development of new drugs, including biological products, for prevention and treatment of certain diseases that, in the aggregate, affect millions of people throughout the world. To be eligible to receive a tropical disease PRV, a drug must be for prevention or treatment of a ‘‘tropical disease’’ as listed under section 524(a)(3) of the FD&C Act. This list can be expanded by the Agency under section 524(a)(3)(S) of the FD&C Act, which authorizes 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 an addition to the list of tropical diseases, approved drug applications for which may be eligible to receive a PRV. Further information about the tropical disease PRV program can be found in the October 6, 2016 (81 FR 69537), guidance for industry ‘‘Tropical Disease Priority Review Vouchers,’’ available at https://www.fda.gov/media/72569/ download. On August 20, 2015, FDA published a final order (80 FR 50559) (August 2015 final order) designating Chagas disease and neurocysticercosis as additions to the list of tropical diseases under section 524 of the FD&C Act. The August 2015 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 (redesignated as section 524(a)(3)(S) of the FD&C Act). Additions by order to the statutory list of PRV-eligible tropical diseases published in the Federal Register can be accessed at https:// www.fda.gov/AboutFDA/CentersOffices/ OfficeofMedicalProductsandTobacco/ CDER/ucm534162.htm. In this document, FDA has applied its August 2015 final order criteria to analyze whether the foodborne E:\FR\FM\15JYN1.SGM 15JYN1 42884 Federal Register / Vol. 85, No. 136 / Wednesday, July 15, 2020 / Notices trematode infections opisthorchiasis and paragonimiasis meet the statutory criteria for addition to the tropical diseases list under section 524 of the FD&C Act. khammond on DSKJM1Z7X2PROD with NOTICES II. Diseases Being Designated FDA has considered all diseases submitted to the public docket (FDA– 2008–N–0567) between June 20, 2018, and November 21, 2018, as potential additions to the list of tropical diseases under section 524 of the FD&C Act, pursuant to the docket review process explained on the Agency’s web page at https://www.fda.gov/AboutFDA/Centers Offices/OfficeofMedicalProductsand Tobacco/CDER/ucm534162.htm. Based on an assessment using the criteria from its August 2015 final order, FDA has determined that the following additional diseases will be designated as additions to the list of tropical diseases for purposes of the tropical disease PRV program under section 524 of the FD&C Act: • Opisthorchiasis • Paragonimiasis The four primary foodborne trematode infections identified by the World Health Organization (WHO) include these two infections, as well as fascioliasis, which was included in the original statutory list of tropical diseases under section 524(a)(3) of the FD&C Act, and clonorchiasis, which FDA has determined does not at this time meet the requirements to be designated as an addition to the list of tropical diseases, approved drug applications for which may be eligible for a PRV under section 524 of the FD&C Act (see FDA’s ‘‘Notice of Decision Not to Designate Clonorchiasis as an Addition to the Current List of Tropical Diseases in the Federal Food, Drug, and Cosmetic Act,’’ published elsewhere in this issue of the Federal Register). Foodborne trematode infections are caused by parasitic trematodes, commonly known as flukes. Trematode infections are naturally transmissible from vertebrate animals to people and back. People become infected through the consumption of raw or undercooked food (e.g., fish, crustaceans, and vegetables), which harbor the minute larval stages of the parasites. FDA’s rationale for adding these diseases to the list is discussed in the analyses that follow. A. Opisthorchiasis Opisthorchiasis is caused by the trematodes Opisthorchis viverrini or O. felineus, acquired by the consumption of raw or undercooked fish (Ref. 1). The natural final hosts of these O. viverrini VerDate Sep<11>2014 17:59 Jul 14, 2020 Jkt 250001 or O. felineus flukes are cats and other fish-eating carnivores (Ref. 1). O. viverrini flukes are reported in Thailand, Laos, Cambodia, and Vietnam while O. felineus flukes are reported in Italy, Germany, Belarus, Russia, Kazakhstan, and Ukraine (Ref. 2). The final location of adult O. viverrini and O. felineus is the smaller bile ducts of the liver (Ref. 3). The symptoms caused by opisthorchiasis are related to inflammation and fibrosis of the tissues adjacent to bile ducts. While the majority of infected individuals are asymptomatic, patients may develop cholangitis, intrahepatic calculi, or cholangiohepatitis. Chronic infection is also associated with the development of cholangiocarcinoma, a severe and fatal form of bile duct cancer, and O. viverrini are recognized by the International Agency for Research on Cancer as Group 1, which means that the agent is classified as carcinogenic to humans (Refs. 4 and 5). There is one FDA-approved treatment for opisthorchiasis, praziquantel, approved in 1982 and indicated for the treatment of infections due to all species of schistosoma and infections due to the liver flukes Clonorchis sinensis and O. viverrini (Ref. 6). 1. No Significant Market in Developed Nations No significant market exists for the treatment or prevention of opisthorchiasis in developed nations. As stated above, opisthorchiasis occurs as a result of O. viverrini and O. felineus (Ref. 7). O. viverrini have been reported in Thailand, Laos, Cambodia, and Vietnam. O. felineus have been reported in Italy, Germany, Belarus, Russia, Kazakhstan, and Ukraine (Ref. 7). Since O. viverrini and O. felineus have a limited geographic range, infections in other countries only occur from movement of infected persons. O. viverrini and O. felineus flukes have a life span of 25 to 30 years, meaning that opisthorchiasis may persist long after a patient is initially infected, however, as described below, these numbers are low in developed countries. Thailand, Laos, Cambodia, Vietnam, Belarus, Russia, Kazakhstan, and Ukraine are not on the World Bank list of high-income economies, which, as described in FDA’s August 2015 final order, will be used as evidence that the country should be considered a ‘‘developed nation’’ for determination of additions to the PRV-eligible tropical diseases list under section 524 of the FD&C Act (Ref. 8). Germany, Greece, and Italy, however, are on the World Bank list of high-income economies, and therefore are considered to be PO 00000 Frm 00066 Fmt 4703 Sfmt 4703 developed nations for the purposes of this order (Ref. 8). In developed countries where O. viverrini and O. felineus are found, the prevalence of opisthorchiasis is very low. There have only been approximately five cases of human infections of O. felineus reported in Germany since the 1980s, and two in Greece in the late 1990s and early 2000s (though one of those infections may have originated elsewhere) (Ref. 9). Italy has seen an increase in reported human infections due to the increased consumption of marinated fillets of raw tench (Tinca tinca), infected with O. felineus (Ref. 9). However, even with this rise in infection rates, the total number of reported opisthorchiasis cases in Italy was only 211 from 2003 to 2011 (Ref. 9). As described in the August 2015 final order, FDA uses a disease prevalence rate of 0.1 percent of the population of developed countries for aiding in the determination of whether a ‘‘significant market’’ may exist for a disease’s treatment. In these three high-income countries where O. viverrini and O. felineus have been reported, the prevalence rates are significantly lower than that which FDA would consider could offer a sufficient market incentive to drive the development of new drug products to prevent or treat opisthorchiasis. Therefore, in developed nations where opisthorchiasis occurs, the prevalence rates of infection are not large enough to create a significant market for treatment. There is currently no estimate of the number of individuals infected with opisthorchiasis in the United States. The available information concerning opisthorchiasis in the United States suggests that the prevalence of opisthorchiasis is much lower than 0.1 percent of the population. Of the infections that do occur in the United States, foodborne trematode infections occur predominantly in immigrants and travelers to and from endemic regions (Refs. 10 and 11). For example, in a retrospective study in one U.S. travel medicine clinic over 6 years, only 17 cases of Opisthorchis spp. and Clonorchis spp. were identified through the review of medical records (Ref. 12). All patients with identified cases were migrants from Laos, Cambodia, Thailand, Vietnam, the former Soviet Union, and Ecuador (Ref. 12). There is evidence that U.S. military personnel were exposed to Opisthorchis spp. and Clonorchis spp. during their service in the Vietnam War (Ref. 13). In one study, there was evidence that veterans were likely previously infected, but patients in the study did not have evidence of ongoing infection, given E:\FR\FM\15JYN1.SGM 15JYN1 Federal Register / Vol. 85, No. 136 / Wednesday, July 15, 2020 / Notices khammond on DSKJM1Z7X2PROD with NOTICES negative stool exams and negative imaging studies, and therefore would not have ongoing infections requiring treatment at present (Ref. 13). As illustrated above, opisthorchiasis occurs rarely in developed nations. The market for drugs for opisthorchiasis in developed nations such as the United States would largely be comprised of immigrants and travelers to and from endemic regions and military populations serving in endemic regions. These markets are unlikely to provide sufficient incentive to encourage development of products to treat or prevent opisthorchiasis. At present, FDA is unaware of any significant funding for opisthorchiasis drug development by the U.S government sources, and opisthorchiasis is not among the Centers for Disease Control and Prevention’s (CDC) list of potential bioterrorism agents. 2. Opisthorchiasis Disproportionately Affects Poor and Marginalized Populations Opisthorchiasis disproportionately affects poor and marginalized populations around the world. Within countries where O. viverrini or O. felineus are reported, opisthorchiasis predominantly occurs in populations living in impoverished settings. For example, in rural northeast Thailand, where the per capita gross domestic product (GDP) is less than $4,000, reported opisthorchiasis prevalence typically exceeds 30 percent of the population (Ref. 14). In contrast, in urban Bangkok, where the per capita GDP is around $15,000, opisthorchiasis prevalence is reported to be less than 5 percent of the population (Refs. 14 and 15). Likewise, in Laos, in the poorer rural southern provinces (poverty rates of 30 to 50 percent), reported opisthorchiasis prevalence is the highest at 20 to 30 percent, whereas in the relatively wealthier urban Vientiane region of Laos (poverty rate less than 20 percent), opisthorchiasis prevalence is reportedly less than 5 percent (Refs. 15 and 16). In Cambodia, a similar trend is noted, where the highest reported prevalence of opisthorchiasis (24 percent) can be found in the rural Kampong Cham and Take´o provinces, where poverty rates exceed 50 percent (Refs. 15 and 17). Opisthorchiasis is also included in the WHO List of Neglected Tropical Diseases (Ref. 18). The WHO Foodborne Disease Burden Epidemiology Reference Group identified opisthorchiasis as an important cause of disability, with an estimated annual incidence of over 16,315 infections and 1,498 deaths, resulting in a global disability-adjusted VerDate Sep<11>2014 17:59 Jul 14, 2020 Jkt 250001 life years (DALYs), which is calculated by adding the number of years of life lost to mortality and the number of years lived with disability due to morbidity due to the illness, of 188,346 (Refs. 19 and 20). Given the above information, FDA concludes that opisthorchiasis disproportionately affects poor and marginalized populations. 3. FDA Determination Given the factors described above, FDA has determined that opisthorchiasis meets both the statutory criteria of ‘‘no significant market in developed nations’’ and ‘‘disproportionately affects poor and marginalized populations.’’ Therefore, FDA is designating opisthorchiasis as an addition to the tropical diseases list under section 524 of the FD&C Act. B. Paragonimiasis Paragonimiasis is caused by Paragonimus spp., which are trematodes acquired through the consumption of raw or undercooked crustaceans (crabs and crayfish) (Ref. 1). The natural final hosts of Paragonimus spp. are cats, dogs, and other crustacean eating carnivores (Ref. 1). Paragonimus spp. are reported in China, the Philippines, Japan, Vietnam, the Republic of Korea (South Korea), Taiwan, Thailand, Central and South America, Africa, and there have been rare reports of these flukes being found in the midwestern United States (Ref. 21). The final location in humans of adult Paragonimus spp. is in lung tissue (Ref. 1). The symptoms caused by paragonimiasis are chronic cough with blood-stained sputum, chest pain, dyspnea, and fever (Ref. 1). Paragonimus spp. can migrate to other parts of the body, e.g., to the brain, where they can cause severe cerebral manifestations (Ref. 1). There are no FDA-approved treatments for paragonimiasis. 1. No Significant Market in Developed Nations FDA is unaware of any significant market for the treatment or prevention of paragonimiasis in the United States or other developed nations. As stated above, paragonimiasis is caused by Paragonimus spp. flukes that have been reported in China, the Philippines, Japan, Vietnam, South Korea, Taiwan, Thailand, Central and South America, Africa, and there have been rare reports of these flukes being found in the midwestern United States. The limited range of Paragonimus spp. means infections outside of these endemic countries only occur from the PO 00000 Frm 00067 Fmt 4703 Sfmt 4703 42885 movement of infected persons. From the countries and regions listed above, South Korea, Taiwan, Uruguay, Chile, and Panama all are on the World Bank’s list of high-income economies (Ref. 8). In developed nations where Paragonimus spp. are found, the prevalence of paragonimiasis is low, according to the published data obtained by the Agency. For example, in Japan, there were 443 patients who were referred to one academic institution and diagnosed as having paragonimiasis from 2001 to 2012 (Ref. 22). The majority of native Japanese patients with paragonimiasis were residents of one island; while one quarter of the cases occurred in immigrants mostly from China, Thailand, and Korea (Ref. 22). In South Korea, the prevalence of paragonimiasis has precipitously dropped as the country has developed; in the 1960s, at least 2 million people were estimated to be infected with paragonimiasis based on intradermal testing; by the 1990s, the prevalence was reduced to 1 percent of the previous estimate (Ref. 23). In a relatively recent review of medical records at another large referral medical center in Seoul, South Korea, only 36 patients were diagnosed with pulmonary paragonimiasis over a 10-year period (1994 to 2004). FDA was unable to find published information about the prevalence of paragonimiasis in humans in Uruguay, Chile, Argentina, or Panama (there are rare reports in the midwestern United States). One study reported 16 cases of paragonimiasis acquired in Missouri from 2008 to 2014, which were associated with consumption of raw crayfish (Ref. 24). The market for drugs for paragonimiasis in most developed nations would largely be comprised of immigrants and travelers from endemic regions. These low prevalence rates in developed countries are unlikely to provide sufficient incentive to encourage development of products to treat or prevent paragonimiasis in developed countries. 2. Paragonimiasis Disproportionately Affects Poor and Marginalized Populations Paragonimiasis disproportionately affects poor and marginalized populations around the world. The true burden of paragonimiasis is unclear given the population it impacts; underreporting is likely, particularly in African regions (Refs. 25 and 26). While epidemiologic data for paragonimiasis are scant, transmission of foodborne trematodes within countries is typically restricted to limited areas and reflects behavioral and ecological patterns E:\FR\FM\15JYN1.SGM 15JYN1 42886 Federal Register / Vol. 85, No. 136 / Wednesday, July 15, 2020 / Notices which are related to socioeconomic status. This includes people’s food habits, methods of food production and preparation, and the distribution of intermediate hosts. For example, food can be contaminated through unhygienic preparation and storage. Furthermore, the consumption of raw fish and crustaceans is a main risk factor for contracting these parasites. The life cycle of the parasites is closely linked with water and sanitation. In populations without access to toilets, or without sewage system infrastructure, unprocessed human and animal fecal waste may be found near water or used as manure or fish feed. This can contaminate drinking water and aquatic vegetables, leading to a continuous cycle of infections. Paragonimiasis is included in the WHO List of Neglected Tropical Diseases (Ref. 18). The WHO Foodborne Disease Burden Epidemiology Reference Group identified paragonimiasis as an important cause of disability, with an estimated annual incidence rate of 139,238 infections and 250 deaths, resulting in global disability-adjusted life years of 1,048,937 (Ref. 27). Given the above information, FDA has concluded that paragonimiasis disproportionately affects poor and marginalized populations. khammond on DSKJM1Z7X2PROD with NOTICES 3. FDA Determination Given the factors described above, FDA has determined that paragonimiasis meets both the statutory criteria of ‘‘no significant market in developed nations,’’ and ‘‘disproportionately affects poor and marginalized populations.’’ Therefore, FDA is designating paragonimiasis as an addition to the tropical diseases list under section 524 of the FD&C Act. III. Process for Requesting Additional Diseases To Be Added to the List The purpose of this order is to add diseases 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. By expanding the list with this order, FDA does not mean to preclude the addition of other diseases to this list in the future. Interested persons may submit requests for additional diseases to be added to the list to the public docket established by FDA for this purpose (see https:// www.regulations.gov, Docket No. FDA– 2008–N–0567). 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 VerDate Sep<11>2014 17:59 Jul 14, 2020 Jkt 250001 information, visit the Agency’s web page at https://www.fda.gov/AboutFDA/ CentersOffices/OfficeofMedical ProductsandTobacco/CDER/ ucm534162.htm. IV. Paperwork Reduction Act This final order 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. 3501–3521). Specifically, facts 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 marked with an asterisk (*) are on display at the Dockets Management Staff (see ADDRESSES) and are available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; they also are available electronically at https:// www.regulations.gov. References without asterisks are not on public display at https://www.regulations.gov because they have copyright restriction. Some may be available at the website address, if listed. References without asterisks are available for viewing only at the Dockets Management Staff. FDA has verified the website addresses, as of the date this document publishes in the Federal Register, but websites are subject to change over time. 1. * WHO, 2018, ‘‘Fact Sheet on Foodborne Trematodiases,’’ accessed October 23, 2019, https://www.who.int/news-room/ fact-sheets/detail/foodbornetrematodiases. 2. * CDC, 2018, ‘‘Parasites—Opisthorchis Infection, Epidemiology & Risk Factors,’’ accessed February 20, 2018, https:// www.cdc.gov/parasites/opisthorchis/ epi.html. 3. * WHO, 2018, ‘‘Fact Sheet on Foodborne Trematodiases,’’ accessed February 8, 2018, https://www.who.int/news-room/ fact-sheets/detail/foodbornetrematodiases. 4. * WHO, International Agency for Research on Cancer (IARC), 2019, ‘‘IARC PO 00000 Frm 00068 Fmt 4703 Sfmt 4703 Monographs on the Identification of Carcinogenic Hazards to Humans, Agents Classified by the IARC Monographs,’’ Vols. 1–124, accessed October 23, 2019, https://monographs.iarc.fr/agentsclassified-by-the-iarc/. 5. * WHO, IARC, 2012, ‘‘IARC Monographs on the Evaluation of Carcinogenic Risks in Humans, Opisthorchis Viverrini and Clonorchis Sinensis,’’ Vol. 100B, 341– 370, accessed October 23, 2019, https:// monographs.iarc.fr/wp-content/uploads/ 2018/06/mono100B-13.pdf. 6. U.S. National Library of Medicine, 2015, ‘‘Label: Biltricide-Praziquantel Tablet, Film Coated,’’ DailyMed. 7. * CDC, 2018, ‘‘Parasites—Opisthorchis Infection: Resources for Health Professionals,’’ accessed October 24, 2019, https://www.cdc.gov/parasites/ opisthorchis/health_professionals/ index.html. 8. The World Bank, 2018, ‘‘World Bank Country and Lending Groups,’’ accessed December 12, 2018, https:// datahelpdesk.worldbank.org/ knowledgebase/articles/906519-worldbank-country-and-lending-groups. 9. Pozio, E., O. Armignacco, F. Ferri, and M. Gomez, 2013, ‘‘Opisthorchis Felineus, an Emerging Infection in Italy and its Implication for the European Union,’’ Acta Tropica, epub ahead of print January 18, 2013, doi: 10.1016/ j.actatropica.2013.01.005. 10. Furst, T., U. Duthaler, B. Sripa, et al., 2012, ‘‘Trematode Infections: Liver and Lung Flukes,’’ Infectious Disease Clinics of North America, 26(2):399–419. 11. Qian, M–B., Y–D. Chen, S. Liang, et al., 2012, ‘‘The Global Epidemiology of Clonorchiasis and Its Relation with Cholangiocarcinoma,’’ Infectious Diseases of Poverty, epub ahead of print October 25, 2012, doi: 10.1186/2049– 9957–1–4. 12. Stauffer, W.M., J.S. Sellman, and P.F. Walker, 2004, ‘‘Billiary Liver Flukes (Opisthorchiasis and Clonorchiasis) in Immigrants in the United States: Often Subtle and Diagnosed Years After Arrival,’’ Journal of Travel Medicine, 11(3):157–159. 13. Psevdos, G., F.M. Ford, and S.T. Hong, 2018, ‘‘Screening U.S. Vietnam Veterans for Liver Fluke Exposure 5 Decades After the End of the War,’’ Infectious Diseases in Clinical Practice, epub ahead of print January 16, 2018, doi: 0.1097/ IPC.0000000000000611. 14. * Office of the National Economic and Social Development Board of Thailand, 2015, ‘‘Gross Regional and Provincial Product, 2016 Edition,’’ accessed October 25, 2019, https:// www.nesdc.go.th/nesdb_en/ewt_w3c/ ewt_dl_link.php?filename=national_ account&nid=4317. 15. Sithithaworn, P., P. Yongvanit, K. Duenngai, et al., 2014, ‘‘Roles of Liver Fluke Infection As Risk Factor for Cholangiocarcinoma,’’ Journal of Hepato-Biliary-Pancreatic Science, epub ahead of print January 10, 2014, doi: 10.1002/jhbp.62. 16. Epprecht, M., N. Minot, R. Dewina, et al., E:\FR\FM\15JYN1.SGM 15JYN1 khammond on DSKJM1Z7X2PROD with NOTICES Federal Register / Vol. 85, No. 136 / Wednesday, July 15, 2020 / Notices and the International Food Policy Research Institute, 2008, ‘‘The Geography of Poverty and Inequality in the Lao PDR,’’ Swiss National Centre of Competence in Research North-South, Geographica Bernensia. 17. Asian Development Bank, 2014, ‘‘Cambodia Country Poverty Analysis, Mandaluyong City, Philippines,’’ Asian Development Bank. 18. * WHO, 2018, ‘‘Neglected Tropical Diseases,’’ accessed October 24, 2019, https://www.who.int/neglected_diseases/ diseases/en/. 19. * WHO, Foodborne Disease Burden Epidemiology Reference Group, 2015, ‘‘WHO Estimates of the Global Burden of Foodborne Diseases 2007–2015,’’ accessed October 24, 2019, https:// www.who.int/foodsafety/publications/ foodborne_disease/fergreport/en/. 20. Yeh, T.C., P.R. Lin, E.R. Chen, and M.F. Shaio, 2001, ‘‘Current Status of Human Parasitic Infections in Taiwan,’’ Journal of Microbiology, Immunology and Infection, 34(3):155–160. 21. * CDC, 2013, ‘‘Parasites—Paragonimias: Epidemiology & Risk Factors,’’ accessed October 24, 2019, https://www.cdc.gov/ parasites/paragonimus/epi.html. 22. Nagayasu, E., A. Yoshida, A. Hombu, et al., 2015, ‘‘Paragonimiasis in Japan: A Twelve-Year Retrospective Case Review, 2001–2012,’’ Internal Medicine, epub ahead of print January 15, 2015, doi: 10.2169/internalmedicine.54.1733. 23. Cho, S.Y., Y. Kong, and S.Y. Kang, 1997, ‘‘Epidemiology of Paragonimiasis in Korea,’’ Southeast Asian Journal of Tropical Medicine and Public Health, 28(Suppl 1):S32–36. 24. Fischer, P.U. and G.J. Weil, 2015, ‘‘North American Paragonimiasis: Epidemiology and Diagnostic Strategies,’’ Expert Review of Anti-Infect Therapy, epub ahead of print April 3, 2015, doi: 10.1586/14787210.2015.1031745. 25. * WHO, Foodborne Disease Burden Epidemiology Reference Group, 2015, ‘‘WHO Estimates of the Global Burden of Foodborne Disease, 2007–2015,’’ accessed October 24, 2019, https:// www.who.int/foodsafety/publications/ foodborne_disease/fergreport/en/. 26. * CDC, 2018, ‘‘Parasites—Clonorchis: Resources for Health Professionals,’’ accessed October 24, 2019, https:// www.cdc.gov/parasites/clonorchis/ health_professionals/. 27. Nakamura-Uchiyama, F., K. Hiromatsu, K. Ishiwata, et al., 2003, ‘‘The Current Status of Parasitic Diseases in Japan,’’ Internal Medicine, 42(3):222–236. Dated: July 8, 2020. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2020–15252 Filed 7–14–20; 8:45 am] BILLING CODE 4164–01–P VerDate Sep<11>2014 17:59 Jul 14, 2020 Jkt 250001 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2020–D–1401] Adaptive and Other Innovative Designs for Effectiveness Studies of New Animal Drugs; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry (GFI) #268 entitled ‘‘Adaptive and Other Innovative Designs for Effectiveness Studies of New Animal Drugs.’’ The draft guidance, if finalized, will describe FDA’s current thinking with respect to assisting sponsors in incorporating complex adaptive and other novel investigation designs into proposed clinical investigation protocols and applications for new animal drugs under the Federal Food, Drug, and Cosmetic Act (FD&C Act). SUMMARY: Submit either electronic or written comments on the draft guidance by October 13, 2020 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance. ADDRESSES: You may submit comments on any guidance at any time as follows: DATES: Electronic Submissions Submit electronic comments in the following way: • Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https:// www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. • If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a PO 00000 Frm 00069 Fmt 4703 Sfmt 4703 42887 written/paper submission and in the manner detailed (see ‘‘Written/Paper Submissions’’ and ‘‘Instructions’’). Written/Paper Submissions Submit written/paper submissions as follows: • Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA–305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. • For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ‘‘Instructions.’’ Instructions: All submissions received must include the Docket No. FDA– 2020–D–1401 for ‘‘Adaptive and Other Innovative Designs for Effectiveness Studies of New Animal Drugs.’’ Received comments will be placed in the docket and, except for those submitted as ‘‘Confidential Submissions,’’ publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240–402–7500. • Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ‘‘THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.’’ The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ‘‘confidential.’’ Any information marked as ‘‘confidential’’ will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https:// www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf. E:\FR\FM\15JYN1.SGM 15JYN1

Agencies

[Federal Register Volume 85, Number 136 (Wednesday, July 15, 2020)]
[Notices]
[Pages 42883-42887]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-15252]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0567]


Designating Additions to the Current List of Tropical Diseases in 
the Federal Food, Drug, and Cosmetic Act

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Federal Food, Drug, and Cosmetic Act (FD&C Act) authorizes 
the Food and Drug Administration (FDA or Agency) to award priority 
review vouchers (PRVs) to tropical disease product applicants when the 
applications meet certain criteria. The FD&C Act lists the diseases 
that are considered tropical diseases for purposes of obtaining PRVs 
and provides for Agency expansion of that list to include other 
diseases that satisfy the definition of ``tropical diseases'' eligible 
for PRVs as set forth in the FD&C Act. The Agency has determined that 
two foodborne trematode infections, opisthorchiasis and paragonimiasis, 
satisfy this definition, and is therefore adding them to the list of 
designated tropical diseases whose product applications may result in 
the award of PRVs. Sponsors submitting certain drug or biological 
product applications for the prevention or treatment of opisthorchiasis 
or paragonimiasis infections may be eligible to receive a PRV if such 
applications are approved by FDA.

DATES: This order is issued on July 15, 2020.

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 Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.

SUPPLEMENTARY INFORMATION: 

Table of Contents

I. Background: Priority Review Voucher Program
II. Diseases Being Designated
    A. Opisthorchiasis
    B. Paragonimiasis
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 
(Pub. L. 110-85), uses a PRV incentive to encourage the development of 
new drugs, including biological products, for prevention and treatment 
of certain diseases that, in the aggregate, affect millions of people 
throughout the world. To be eligible to receive a tropical disease PRV, 
a drug must be for prevention or treatment of a ``tropical disease'' as 
listed under section 524(a)(3) of the FD&C Act. This list can be 
expanded by the Agency under section 524(a)(3)(S) of the FD&C Act, 
which authorizes 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 an addition to the list of tropical diseases, approved drug 
applications for which may be eligible to receive a PRV. Further 
information about the tropical disease PRV program can be found in the 
October 6, 2016 (81 FR 69537), guidance for industry ``Tropical Disease 
Priority Review Vouchers,'' available at https://www.fda.gov/media/72569/download.
    On August 20, 2015, FDA published a final order (80 FR 50559) 
(August 2015 final order) designating Chagas disease and 
neurocysticercosis as additions to the list of tropical diseases under 
section 524 of the FD&C Act. The August 2015 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 (redesignated as section 
524(a)(3)(S) of the FD&C Act). Additions by order to the statutory list 
of PRV-eligible tropical diseases published in the Federal Register can 
be accessed at https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm534162.htm.
    In this document, FDA has applied its August 2015 final order 
criteria to analyze whether the foodborne

[[Page 42884]]

trematode infections opisthorchiasis and paragonimiasis meet the 
statutory criteria for addition to the tropical diseases list under 
section 524 of the FD&C Act.

II. Diseases Being Designated

    FDA has considered all diseases submitted to the public docket 
(FDA-2008-N-0567) between June 20, 2018, and November 21, 2018, as 
potential additions to the list of tropical diseases under section 524 
of the FD&C Act, pursuant to the docket review process explained on the 
Agency's web page at https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm534162.htm. Based on an 
assessment using the criteria from its August 2015 final order, FDA has 
determined that the following additional diseases will be designated as 
additions to the list of tropical diseases for purposes of the tropical 
disease PRV program under section 524 of the FD&C Act:

 Opisthorchiasis
 Paragonimiasis

    The four primary foodborne trematode infections identified by the 
World Health Organization (WHO) include these two infections, as well 
as fascioliasis, which was included in the original statutory list of 
tropical diseases under section 524(a)(3) of the FD&C Act, and 
clonorchiasis, which FDA has determined does not at this time meet the 
requirements to be designated as an addition to the list of tropical 
diseases, approved drug applications for which may be eligible for a 
PRV under section 524 of the FD&C Act (see FDA's ``Notice of Decision 
Not to Designate Clonorchiasis as an Addition to the Current List of 
Tropical Diseases in the Federal Food, Drug, and Cosmetic Act,'' 
published elsewhere in this issue of the Federal Register).
    Foodborne trematode infections are caused by parasitic trematodes, 
commonly known as flukes. Trematode infections are naturally 
transmissible from vertebrate animals to people and back. People become 
infected through the consumption of raw or undercooked food (e.g., 
fish, crustaceans, and vegetables), which harbor the minute larval 
stages of the parasites.
    FDA's rationale for adding these diseases to the list is discussed 
in the analyses that follow.

A. Opisthorchiasis

    Opisthorchiasis is caused by the trematodes Opisthorchis viverrini 
or O. felineus, acquired by the consumption of raw or undercooked fish 
(Ref. 1). The natural final hosts of these O. viverrini or O. felineus 
flukes are cats and other fish-eating carnivores (Ref. 1). O. viverrini 
flukes are reported in Thailand, Laos, Cambodia, and Vietnam while O. 
felineus flukes are reported in Italy, Germany, Belarus, Russia, 
Kazakhstan, and Ukraine (Ref. 2).
    The final location of adult O. viverrini and O. felineus is the 
smaller bile ducts of the liver (Ref. 3). The symptoms caused by 
opisthorchiasis are related to inflammation and fibrosis of the tissues 
adjacent to bile ducts. While the majority of infected individuals are 
asymptomatic, patients may develop cholangitis, intrahepatic calculi, 
or cholangiohepatitis. Chronic infection is also associated with the 
development of cholangiocarcinoma, a severe and fatal form of bile duct 
cancer, and O. viverrini are recognized by the International Agency for 
Research on Cancer as Group 1, which means that the agent is classified 
as carcinogenic to humans (Refs. 4 and 5).
    There is one FDA-approved treatment for opisthorchiasis, 
praziquantel, approved in 1982 and indicated for the treatment of 
infections due to all species of schistosoma and infections due to the 
liver flukes Clonorchis sinensis and O. viverrini (Ref. 6).
1. No Significant Market in Developed Nations
    No significant market exists for the treatment or prevention of 
opisthorchiasis in developed nations. As stated above, opisthorchiasis 
occurs as a result of O. viverrini and O. felineus (Ref. 7). O. 
viverrini have been reported in Thailand, Laos, Cambodia, and Vietnam. 
O. felineus have been reported in Italy, Germany, Belarus, Russia, 
Kazakhstan, and Ukraine (Ref. 7). Since O. viverrini and O. felineus 
have a limited geographic range, infections in other countries only 
occur from movement of infected persons. O. viverrini and O. felineus 
flukes have a life span of 25 to 30 years, meaning that opisthorchiasis 
may persist long after a patient is initially infected, however, as 
described below, these numbers are low in developed countries.
    Thailand, Laos, Cambodia, Vietnam, Belarus, Russia, Kazakhstan, and 
Ukraine are not on the World Bank list of high-income economies, which, 
as described in FDA's August 2015 final order, will be used as evidence 
that the country should be considered a ``developed nation'' for 
determination of additions to the PRV-eligible tropical diseases list 
under section 524 of the FD&C Act (Ref. 8). Germany, Greece, and Italy, 
however, are on the World Bank list of high-income economies, and 
therefore are considered to be developed nations for the purposes of 
this order (Ref. 8).
    In developed countries where O. viverrini and O. felineus are 
found, the prevalence of opisthorchiasis is very low. There have only 
been approximately five cases of human infections of O. felineus 
reported in Germany since the 1980s, and two in Greece in the late 
1990s and early 2000s (though one of those infections may have 
originated elsewhere) (Ref. 9). Italy has seen an increase in reported 
human infections due to the increased consumption of marinated fillets 
of raw tench (Tinca tinca), infected with O. felineus (Ref. 9). 
However, even with this rise in infection rates, the total number of 
reported opisthorchiasis cases in Italy was only 211 from 2003 to 2011 
(Ref. 9). As described in the August 2015 final order, FDA uses a 
disease prevalence rate of 0.1 percent of the population of developed 
countries for aiding in the determination of whether a ``significant 
market'' may exist for a disease's treatment. In these three high-
income countries where O. viverrini and O. felineus have been reported, 
the prevalence rates are significantly lower than that which FDA would 
consider could offer a sufficient market incentive to drive the 
development of new drug products to prevent or treat opisthorchiasis. 
Therefore, in developed nations where opisthorchiasis occurs, the 
prevalence rates of infection are not large enough to create a 
significant market for treatment.
    There is currently no estimate of the number of individuals 
infected with opisthorchiasis in the United States. The available 
information concerning opisthorchiasis in the United States suggests 
that the prevalence of opisthorchiasis is much lower than 0.1 percent 
of the population. Of the infections that do occur in the United 
States, foodborne trematode infections occur predominantly in 
immigrants and travelers to and from endemic regions (Refs. 10 and 11). 
For example, in a retrospective study in one U.S. travel medicine 
clinic over 6 years, only 17 cases of Opisthorchis spp. and Clonorchis 
spp. were identified through the review of medical records (Ref. 12). 
All patients with identified cases were migrants from Laos, Cambodia, 
Thailand, Vietnam, the former Soviet Union, and Ecuador (Ref. 12).
    There is evidence that U.S. military personnel were exposed to 
Opisthorchis spp. and Clonorchis spp. during their service in the 
Vietnam War (Ref. 13). In one study, there was evidence that veterans 
were likely previously infected, but patients in the study did not have 
evidence of ongoing infection, given

[[Page 42885]]

negative stool exams and negative imaging studies, and therefore would 
not have ongoing infections requiring treatment at present (Ref. 13).
    As illustrated above, opisthorchiasis occurs rarely in developed 
nations. The market for drugs for opisthorchiasis in developed nations 
such as the United States would largely be comprised of immigrants and 
travelers to and from endemic regions and military populations serving 
in endemic regions. These markets are unlikely to provide sufficient 
incentive to encourage development of products to treat or prevent 
opisthorchiasis. At present, FDA is unaware of any significant funding 
for opisthorchiasis drug development by the U.S government sources, and 
opisthorchiasis is not among the Centers for Disease Control and 
Prevention's (CDC) list of potential bioterrorism agents.
2. Opisthorchiasis Disproportionately Affects Poor and Marginalized 
Populations
    Opisthorchiasis disproportionately affects poor and marginalized 
populations around the world. Within countries where O. viverrini or O. 
felineus are reported, opisthorchiasis predominantly occurs in 
populations living in impoverished settings. For example, in rural 
northeast Thailand, where the per capita gross domestic product (GDP) 
is less than $4,000, reported opisthorchiasis prevalence typically 
exceeds 30 percent of the population (Ref. 14). In contrast, in urban 
Bangkok, where the per capita GDP is around $15,000, opisthorchiasis 
prevalence is reported to be less than 5 percent of the population 
(Refs. 14 and 15). Likewise, in Laos, in the poorer rural southern 
provinces (poverty rates of 30 to 50 percent), reported opisthorchiasis 
prevalence is the highest at 20 to 30 percent, whereas in the 
relatively wealthier urban Vientiane region of Laos (poverty rate less 
than 20 percent), opisthorchiasis prevalence is reportedly less than 5 
percent (Refs. 15 and 16). In Cambodia, a similar trend is noted, where 
the highest reported prevalence of opisthorchiasis (24 percent) can be 
found in the rural Kampong Cham and Tak[eacute]o provinces, where 
poverty rates exceed 50 percent (Refs. 15 and 17).
    Opisthorchiasis is also included in the WHO List of Neglected 
Tropical Diseases (Ref. 18). The WHO Foodborne Disease Burden 
Epidemiology Reference Group identified opisthorchiasis as an important 
cause of disability, with an estimated annual incidence of over 16,315 
infections and 1,498 deaths, resulting in a global disability-adjusted 
life years (DALYs), which is calculated by adding the number of years 
of life lost to mortality and the number of years lived with disability 
due to morbidity due to the illness, of 188,346 (Refs. 19 and 20).
    Given the above information, FDA concludes that opisthorchiasis 
disproportionately affects poor and marginalized populations.
3. FDA Determination
    Given the factors described above, FDA has determined that 
opisthorchiasis meets both the statutory criteria of ``no significant 
market in developed nations'' and ``disproportionately affects poor and 
marginalized populations.'' Therefore, FDA is designating 
opisthorchiasis as an addition to the tropical diseases list under 
section 524 of the FD&C Act.

B. Paragonimiasis

    Paragonimiasis is caused by Paragonimus spp., which are trematodes 
acquired through the consumption of raw or undercooked crustaceans 
(crabs and crayfish) (Ref. 1). The natural final hosts of Paragonimus 
spp. are cats, dogs, and other crustacean eating carnivores (Ref. 1). 
Paragonimus spp. are reported in China, the Philippines, Japan, 
Vietnam, the Republic of Korea (South Korea), Taiwan, Thailand, Central 
and South America, Africa, and there have been rare reports of these 
flukes being found in the midwestern United States (Ref. 21). The final 
location in humans of adult Paragonimus spp. is in lung tissue (Ref. 
1). The symptoms caused by paragonimiasis are chronic cough with blood-
stained sputum, chest pain, dyspnea, and fever (Ref. 1). Paragonimus 
spp. can migrate to other parts of the body, e.g., to the brain, where 
they can cause severe cerebral manifestations (Ref. 1). There are no 
FDA-approved treatments for paragonimiasis.
1. No Significant Market in Developed Nations
    FDA is unaware of any significant market for the treatment or 
prevention of paragonimiasis in the United States or other developed 
nations. As stated above, paragonimiasis is caused by Paragonimus spp. 
flukes that have been reported in China, the Philippines, Japan, 
Vietnam, South Korea, Taiwan, Thailand, Central and South America, 
Africa, and there have been rare reports of these flukes being found in 
the midwestern United States. The limited range of Paragonimus spp. 
means infections outside of these endemic countries only occur from the 
movement of infected persons. From the countries and regions listed 
above, South Korea, Taiwan, Uruguay, Chile, and Panama all are on the 
World Bank's list of high-income economies (Ref. 8).
    In developed nations where Paragonimus spp. are found, the 
prevalence of paragonimiasis is low, according to the published data 
obtained by the Agency. For example, in Japan, there were 443 patients 
who were referred to one academic institution and diagnosed as having 
paragonimiasis from 2001 to 2012 (Ref. 22). The majority of native 
Japanese patients with paragonimiasis were residents of one island; 
while one quarter of the cases occurred in immigrants mostly from 
China, Thailand, and Korea (Ref. 22). In South Korea, the prevalence of 
paragonimiasis has precipitously dropped as the country has developed; 
in the 1960s, at least 2 million people were estimated to be infected 
with paragonimiasis based on intradermal testing; by the 1990s, the 
prevalence was reduced to 1 percent of the previous estimate (Ref. 23). 
In a relatively recent review of medical records at another large 
referral medical center in Seoul, South Korea, only 36 patients were 
diagnosed with pulmonary paragonimiasis over a 10-year period (1994 to 
2004). FDA was unable to find published information about the 
prevalence of paragonimiasis in humans in Uruguay, Chile, Argentina, or 
Panama (there are rare reports in the midwestern United States). One 
study reported 16 cases of paragonimiasis acquired in Missouri from 
2008 to 2014, which were associated with consumption of raw crayfish 
(Ref. 24).
    The market for drugs for paragonimiasis in most developed nations 
would largely be comprised of immigrants and travelers from endemic 
regions. These low prevalence rates in developed countries are unlikely 
to provide sufficient incentive to encourage development of products to 
treat or prevent paragonimiasis in developed countries.
2. Paragonimiasis Disproportionately Affects Poor and Marginalized 
Populations
    Paragonimiasis disproportionately affects poor and marginalized 
populations around the world. The true burden of paragonimiasis is 
unclear given the population it impacts; under-reporting is likely, 
particularly in African regions (Refs. 25 and 26). While epidemiologic 
data for paragonimiasis are scant, transmission of foodborne trematodes 
within countries is typically restricted to limited areas and reflects 
behavioral and ecological patterns

[[Page 42886]]

which are related to socioeconomic status. This includes people's food 
habits, methods of food production and preparation, and the 
distribution of intermediate hosts. For example, food can be 
contaminated through unhygienic preparation and storage. Furthermore, 
the consumption of raw fish and crustaceans is a main risk factor for 
contracting these parasites. The life cycle of the parasites is closely 
linked with water and sanitation. In populations without access to 
toilets, or without sewage system infrastructure, unprocessed human and 
animal fecal waste may be found near water or used as manure or fish 
feed. This can contaminate drinking water and aquatic vegetables, 
leading to a continuous cycle of infections.
    Paragonimiasis is included in the WHO List of Neglected Tropical 
Diseases (Ref. 18). The WHO Foodborne Disease Burden Epidemiology 
Reference Group identified paragonimiasis as an important cause of 
disability, with an estimated annual incidence rate of 139,238 
infections and 250 deaths, resulting in global disability-adjusted life 
years of 1,048,937 (Ref. 27). Given the above information, FDA has 
concluded that paragonimiasis disproportionately affects poor and 
marginalized populations.
3. FDA Determination
    Given the factors described above, FDA has determined that 
paragonimiasis meets both the statutory criteria of ``no significant 
market in developed nations,'' and ``disproportionately affects poor 
and marginalized populations.'' Therefore, FDA is designating 
paragonimiasis as an addition to the tropical diseases list under 
section 524 of the FD&C Act.

III. Process for Requesting Additional Diseases To Be Added to the List

    The purpose of this order is to add diseases 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. By expanding the list with this order, 
FDA does not mean to preclude the addition of other diseases to this 
list in the future. Interested persons may submit requests for 
additional diseases to be added to the list to the public docket 
established by FDA for this purpose (see https://www.regulations.gov, 
Docket No. FDA-2008-N-0567). 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, visit the Agency's web page at https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm534162.htm.

IV. Paperwork Reduction Act

    This final order 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. 3501-3521). 
Specifically, facts 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 marked with an asterisk (*) are on display 
at the Dockets Management Staff (see ADDRESSES) and are available for 
viewing by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public 
display at https://www.regulations.gov because they have copyright 
restriction. Some may be available at the website address, if listed. 
References without asterisks are available for viewing only at the 
Dockets Management Staff. FDA has verified the website addresses, as of 
the date this document publishes in the Federal Register, but websites 
are subject to change over time.

1. * WHO, 2018, ``Fact Sheet on Foodborne Trematodiases,'' accessed 
October 23, 2019, https://www.who.int/news-room/fact-sheets/detail/foodborne-trematodiases.
2. * CDC, 2018, ``Parasites--Opisthorchis Infection, Epidemiology & 
Risk Factors,'' accessed February 20, 2018, https://www.cdc.gov/parasites/opisthorchis/epi.html.
3. * WHO, 2018, ``Fact Sheet on Foodborne Trematodiases,'' accessed 
February 8, 2018, https://www.who.int/news-room/fact-sheets/detail/foodborne-trematodiases.
4. * WHO, International Agency for Research on Cancer (IARC), 2019, 
``IARC Monographs on the Identification of Carcinogenic Hazards to 
Humans, Agents Classified by the IARC Monographs,'' Vols. 1-124, 
accessed October 23, 2019, https://monographs.iarc.fr/agents-classified-by-the-iarc/.
5. * WHO, IARC, 2012, ``IARC Monographs on the Evaluation of 
Carcinogenic Risks in Humans, Opisthorchis Viverrini and Clonorchis 
Sinensis,'' Vol. 100B, 341-370, accessed October 23, 2019, https://monographs.iarc.fr/wp-content/uploads/2018/06/mono100B-13.pdf.
6. U.S. National Library of Medicine, 2015, ``Label: Biltricide-
Praziquantel Tablet, Film Coated,'' DailyMed.
7. * CDC, 2018, ``Parasites--Opisthorchis Infection: Resources for 
Health Professionals,'' accessed October 24, 2019, https://www.cdc.gov/parasites/opisthorchis/health_professionals/.
8. The World Bank, 2018, ``World Bank Country and Lending Groups,'' 
accessed December 12, 2018, https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups.
9. Pozio, E., O. Armignacco, F. Ferri, and M. Gomez, 2013, 
``Opisthorchis Felineus, an Emerging Infection in Italy and its 
Implication for the European Union,'' Acta Tropica, epub ahead of 
print January 18, 2013, doi: 10.1016/j.actatropica.2013.01.005.
10. Furst, T., U. Duthaler, B. Sripa, et al., 2012, ``Trematode 
Infections: Liver and Lung Flukes,'' Infectious Disease Clinics of 
North America, 26(2):399-419.
11. Qian, M-B., Y-D. Chen, S. Liang, et al., 2012, ``The Global 
Epidemiology of Clonorchiasis and Its Relation with 
Cholangiocarcinoma,'' Infectious Diseases of Poverty, epub ahead of 
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    Dated: July 8, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-15252 Filed 7-14-20; 8:45 am]
BILLING CODE 4164-01-P

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