Document ID: FDA-2008-N-0567-0011
Agency: fda
Document Type: Rule
Title: Designating Additions to the Current List of Tropical Diseases in the Federal
Food, Drug, and Cosmetic Act
Posted Date: 2015-08-20T04:00Z

[Federal Register Volume 80, Number 161 (Thursday, August 20, 2015)]
[Rules and Regulations]
[Pages 50559-50564]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-20554]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 317

[Docket No. FDA-2008-N-0567]
RIN 0910-AG37

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 (the 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 to be tropical diseases for purposes of 
obtaining PRVs, and also provides for Agency expansion of that list to 
include other diseases that satisfy the definition of ``tropical 
diseases'' as set forth in the FD&C Act. FDA has determined that Chagas 
disease and neurocysticercosis satisfy this definition, and therefore 
is adding them to the list of designated tropical diseases whose 
product applications may result in the award of PRVs. Sponsors 
submitting certain applications for the treatment of Chagas disease and 
neurocysticercosis may be eligible to receive a PRV if such 
applications are approved by FDA.

DATES: This order is effective August 20, 2015.

ADDRESSES: Submit electronic comments on additional diseases suggested 
for designation to www.regulations.gov. Submit written comments on 
additional diseases suggested for designation to the Division of 
Dockets Management (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: Kristiana Brugger, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 6262, Silver Spring, MD 20993-0002, 301-
796-3601; 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. Criteria for Expansion of the List of Tropical Diseases
    A. No Significant Market in Developed Nations
    B. Disproportionately Affects Poor and Marginalized Populations
III. Diseases Being Designated
    A. Chagas Disease
    B. Neurocysticercosis
IV. Process for Requesting Additional Diseases To Be Added to the 
List
V. Paperwork Reduction Act
VI. References

I. Background: Priority Review Voucher Program

    Much of the global burden of disease falls on populations who lack 
the resources to develop, encourage development of, or purchase disease 
preventions or treatments. For this reason, many of the diseases 
afflicting these populations do not receive the same level of 
innovation investment as diseases afflicting wealthier or more 
empowered populations.
    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), is designed to address the lack of treatment development 
incentives for such tropical diseases. It uses a PRV incentive to 
encourage the development of new drugs for prevention and treatment of 
certain diseases that, in the aggregate, affect millions of people 
throughout the world. Specifically, section 524 of the FD&C Act defines 
the term ``tropical disease product application'' and sets forth 
criteria which, if met, enable those who submit an application for a 
tropical disease product to be eligible to receive a PRV upon approval 
of that tropical disease product application. To be eligible for a PRV, 
the tropical disease product application must meet all of the following 
criteria:
     The application must be a ``human drug application,'' as 
defined in section 735(1) of the FD&C Act (21 U.S.C. 379g(1)).
     The application must be for the ``prevention or treatment 
of a tropical disease,'' as defined by statute.
     The application must be deemed eligible for priority 
review by the Secretary of HHS.
     The application must be approved after the date of 
enactment of FDAAA (i.e., September 27, 2007) for use in the 
prevention, detection, or treatment of a tropical disease.
     The application must be for ``a human drug, no active 
ingredient (including any ester or salt of the active ingredient) of 
which has been approved in any other application under section 
505(b)(1) [21 U.S.C. 355(b)(1)] or section 351 of the [PHS Act].''
    Section 524(a)(4) of the FD&C Act. In particular, the requirement 
that an application must be eligible for priority review demonstrates 
the PRV program's intent to reward tropical disease product 
applications that have the potential to demonstrate significant 
improvements in safety or effectiveness in the treatment or prevention 
of tropical diseases (Ref. 1).
    FDA will award a PRV to the application holder upon the approval of 
a qualifying tropical disease product application that meets the 
criteria previously listed. The voucher entitles the holder to a 
priority review of a human drug application, submitted under section 
505(b)(1) of the FD&C Act or section 351 of the PHS Act, of the voucher 
holder's choosing. Once awarded to the application holder, the PRV may 
be transferred to another entity, and the original holder may receive 
consideration (including payment) for the transfer. To redeem the 
voucher, a PRV holder must notify FDA of its intent to use the PRV at 
least 90 days prior to the submission of the application for which the 
PRV will be used. This notification constitutes a legally binding 
agreement to pay the user fee that must be applied to applications 
using a PRV.
    Section 524(a)(3) of the FD&C Act lists the following diseases as 
tropical diseases qualifying for a PRV:

 Tuberculosis

[[Page 50560]]

 Malaria
 Blinding trachoma
 Buruli ulcer
 Cholera
 Dengue/Dengue haemorrhagic fever
 Dracunculiasis (guinea-worm disease)
 Fascioliasis
 Human African trypanosomiasis
 Leishmaniasis
 Leprosy
 Lymphatic filariasis
 Onchocerciasis
 Schistosomiasis
 Soil transmitted helminthiasis
 Yaws
 Filoviruses

In addition, section 524(a)(3)(R) of the FD&C Act authorizes the 
Secretary to expand by order the list of tropical diseases to include 
``[a]ny other infectious disease for which there is no significant 
market in developed nations and that disproportionately affects poor 
and marginalized populations[,]'' and that is the purpose of this 
order.

II. Criteria for Expansion of the List of Tropical Diseases

    On December 12, 2008, FDA convened a public hearing, at which the 
public provided suggestions regarding the following topics: (1) 
Criteria that should be used to determine the eligibility of an 
infectious disease for designation as a tropical disease, (2) the 
process that should be used to make tropical disease designations, and 
(3) recommendations for specific diseases that should be designated as 
tropical diseases. A number of participants in the public meeting 
commented that, given the lack of definitive data for some diseases, as 
well as the lack of consensus on how these criteria should be defined, 
FDA should use a flexible approach in determining whether specific 
diseases meet the criteria.
    FDA agrees with the use of a flexible approach to tropical disease 
designation and is proposing that a scientifically informed, 
qualitative assessment of disease candidates is appropriate. FDA also 
is establishing a public docket that will continuously remain open to 
receive future suggestions for tropical disease designations under 
section 524 of the FD&C Act. The Agency proposes to review the contents 
of this public docket periodically and to take action to designate 
additional diseases when appropriate.
    As stated previously, section 524(a)(3)(R) of the FD&C Act 
authorizes the Secretary 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.'' In the following paragraphs, FDA sets forth 
its interpretation of this provision and the criteria we propose to use 
in determining which diseases may be designated by order of the 
Secretary as ``tropical diseases'' under section 524.

A. No Significant Market in Developed Nations

1. ``Developed Nations''
    In interpreting the term ``developed nations,'' FDA acknowledges at 
the outset that the standards for determining a nation's level of 
development, as well as the threshold for a ``developed'' country, are 
the subject of debate. Some nations may score well in some markers of 
development (e.g., gross domestic product) and poorly in others (e.g., 
sanitation), leading to disagreements regarding which measures of 
development should serve as dominant indicators. After also examining 
the International Monetary Fund (IMF)'s list of advanced economies 
(Ref. 2) and the United Nations (U.N.)'s human development index (Ref. 
3), the Agency is proposing to use a country's presence on the World 
Bank's \1\ list of ``high income economies'' (Ref. 4) as evidence that 
the country should be considered a ``developed nation'' for ``tropical 
disease'' determination purposes. Similarly, FDA will use a country's 
presence on the World Bank's list of ``low income economies'' (id.) as 
evidence that the country should not be considered a ``developed 
nation'' for purposes of ``tropical disease'' determination.
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    \1\ The ``World Bank'' is a term used to refer collectively to 
the International Development Association and the International Bank 
for Reconstruction and Development, which are two of the five 
organizations that comprise the World Bank Group.
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    FDA recognizes that there is a correlation between economic 
strength (particularly purchasing power) and the market incentive for 
drug creation: People in high-income economies are more likely to be 
able to afford disease treatments and, thus, drug companies have an 
incentive to create products that will be in demand in those countries. 
The World Bank list of high-income economies is calculated based on 
gross national income per capita, and, importantly, it thus reflects 
wealth as a primary basis for categorization. FDA's recognition of the 
role of wealth is why we deemed the U.N. development index less 
helpful: It measures development across a broad array of categories 
(e.g., mean years of schooling) that, while informative, are less 
directly correlated with the drug development incentives reflected in 
the statutory scheme. Indeed, the U.N. itself has acknowledged that 
``[t]he [human development index] was created to emphasize that people 
and their capabilities should be the ultimate criteria for assessing 
the development of a country, not economic growth alone'' (Ref. 5). And 
although the IMF's list of ``advanced economies'' reflects purchasing 
power to some degree, the World Bank calculus is more transparent and 
predictable than the IMF's calculus, and the U.S. government routinely 
uses the World Bank lists when determining a country's eligibility for 
Generalized System of Preferences benefits for trade in goods (Ref. 6).
2. ``No Significant Market''
    The list of tropical diseases in section 524(a)(3) of the FD&C 
includes ``[a]ny other infectious disease for which there is no 
significant market in developed nations. . .designated by order of the 
Secretary.'' As an initial matter, the Agency notes that ``infectious 
diseases,'' as such do not have markets--but drugs for the treatment or 
prevention of infectious diseases do. Because the statute offers 
vouchers for applications for drugs for either the treatment or 
prevention of infectious diseases, it is reasonable to assume that ``no 
significant market'' can refer to drugs for the treatment or prevention 
of infectious diseases. Thus, FDA will analyze the market for drugs for 
both the treatment and prevention of infectious diseases for a 
particular infectious disease.
    The threshold for what constitutes a ``significant market'' for 
drugs for the treatment or prevention of infectious diseases is 
difficult to quantify. Because of the challenges in providing a rigid 
definition of this term, FDA proposes that the following factors be 
considered in determining whether a ``significant market'' exists in 
developed countries.
a. Occurrence of the Disease in Developed Nations
    As discussed previously, market forces are important drivers of 
drug development. The purpose of section 524 of the FD&C Act is to 
provide an incentive (through a PRV) for innovation where there 
otherwise would be an insufficient financial or market incentive to 
invest in developing drugs for tropical diseases. The market for many 
FDA-approved products includes situations in which individuals (often 
reimbursed by their insurers) purchase the products for use by a 
specific patient. This reflects what we will refer to as the ``direct'' 
market, and the direct market for a drug in a

[[Page 50561]]

developed country can often be estimated by assessing the occurrence of 
a particular disease in that country.\2\
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    \2\ Exceptions may occur for diseases that have a low incidence 
in developed countries through use of preventive drugs or biologics. 
Thus, although the disease incidence is lower in developed countries 
these are less likely to be the types of diseases for which section 
524 of the FD&C Act is intended to spur innovation.
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    If the prevalence of a disease in developed countries is less than 
0.1 percent of the population of those countries, it is unlikely that 
ordinary market forces will offer a sufficient incentive to drive the 
development of new preventions or treatments. Thus, it is unlikely that 
there will be a ``significant market'' for the disease's treatment in 
those countries. Accordingly, FDA has decided to use a disease 
prevalence rate of 0.1 percent of the population as a factor for aiding 
in the determination of whether a ``significant market'' may exist for 
a disease's treatment.
b. The Existence of a Sizeable Indirect Market for the Tropical Disease 
Drug (e.g., Government, Including the Military) That Would Constitute a 
Financial Incentive for Drug Development
    As discussed previously, the market for many FDA-approved products 
is the ``direct'' market, involving patients purchasing drugs for their 
own use. However, some drugs may have a sizeable ``indirect'' market 
composed of, for example, government entities or nongovernmental 
organizations that wish to purchase and distribute a drug for the 
treatment or prevention of an infectious disease, often for public 
health reasons, to a particular group of people. Indeed, for some 
diseases identified as high priorities for public health preparedness, 
governmental entities have initiated programs to provide support for 
product development and/or stockpiling (Ref. 7).\3\ In such cases, FDA 
would consider that market as a factor in determining whether a 
significant market for a drug for the treatment or prevention of an 
infectious diseases disease exists in developed nations.
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    \3\ For example, certain diseases have been prioritized for 
medical countermeasure development and investment (see Ref. 7) or 
are listed as priority pathogens by government entities such as the 
National Institutes of Health (NIH)/National Institute of Allergy 
and Infectious Diseases (NIAID), Center for Disease Control or 
Prevention, and military programs (Refs. 8, 9, and 10). These and 
other indications of potential priority designation that could 
affect governmental resource allocation may be taken into account in 
assessment of whether a market exists in developed countries.
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B. Disproportionately Affects Poor and Marginalized Populations

    As with the term ``no significant market in developed nations,'' 
FDA has elected to analyze multiple factors--none of which, alone, 
invariably will be outcome-determinative--in assessing whether a given 
disease meets the requirement of ``disproportionately affects poor and 
marginalized populations'' for classification as a ``tropical disease'' 
under section 524 of the FD&C Act. Those factors are the following:
1. The Proportion of Global Disability-Adjusted Life Years for the 
Disease That Is Attributable to Developing Countries
    A disability-adjusted life year (DALY) measurement is not a direct 
measure of the prevalence of the disease; rather, it is a measure of 
the impact of that disease on a given population. ``One DALY can be 
thought of as one lost year of 'healthy' life'' (Ref. 11). An estimate 
of disease-related morbidity (a term which, as used in this order, 
refers to the state of being diseased (see Ref. 12)) and mortality in 
affected countries thus can be made by assessing available information 
about the DALY burden of a particular disease. ``DALYs for a disease or 
health condition are calculated as the sum of the Years of Life Lost. . 
.due to premature mortality in the population and the Years Lost due to 
Disability. . .for people living with the health condition or its 
consequences'' (Ref. 11). DALYs are an important measurement, enabling 
FDA to weigh ``tropical disease'' eligibility for those diseases that, 
although they may be present to some degree in developed countries 
(e.g., because of travel or immigration), cause much more harm to the 
public health of developing countries.
2. The Relative Burden of the Disease in the Most Impoverished 
Populations Within the Countries in Which It Is Found
    If a disease's prevalence is high in populations who cannot afford 
treatment and low in populations that can, there likely will be little 
market incentive for drug companies to create new treatments. In light 
of section 524 of the FD&C Act's intent to create treatment development 
incentives, as well as its clear goal of improving the health of 
impoverished populations, FDA will consider the demographic 
distribution of a disease in determining whether it should be 
designated as a ``tropical disease'' for the purposes of section 524 of 
the FD&C Act.
3. The Relative Burden of the Disease in Infants, Children, or Other 
Marginalized Segments of the Population (e.g., Women, the Elderly) 
Within the Countries in Which It Is Found
    One of the clear goals of section 524 of the FD&C Act is improving 
the health of marginalized populations, who generally suffer poorer 
health outcomes than their non-marginalized neighbors, even within the 
same country. To ``marginalize'' is to place (or keep) a person or 
population in a powerless or unimportant position (see, e.g., Ref. 13). 
Individuals or groups may be marginalized for any number of reasons, 
including, for example, gender, age, or extreme poverty. Marginalized 
populations generally lack a meaningful voice in societal 
decisionmaking, including decisions relating to the acquisition, 
distribution, and use of health resources. These populations, 
therefore, are less likely to have their health needs met and less 
likely to have the resources or political power needed to effect change 
in those aspects of health policy that most affect them--including 
incentivizing governments or private industry to offer disease 
treatments. Understanding the relative prevalence of a disease in these 
populations will help FDA determine whether treatment development for 
that disease would be spurred by the provision of section 524 of the 
FD&C Act's PRV incentive.
4. Designation by the World Health Organization as a Neglected Tropical 
Disease
    The World Health Organization (WHO), in its role as the directing 
and coordinating authority on international health within the U.N. 
system, has identified a list of diseases that it refers to as 
``neglected tropical diseases'' (Ref. 14). According to the WHO, these 
diseases ``are strongly associated with poverty'' and tend to affect 
those with ``little political voice''; rarely receive the attention of 
disease treatment innovators or the broader international community; 
and often flourish in tropical climates (id.). The WHO's list includes 
12 of the 17 enumerated diseases in section 524(a)(3) of the FD&C Act 
(see Ref. 15). Because the WHO's list of ``neglected tropical 
diseases'' includes many of the types of diseases for which section 524 
was designed to incentivize treatment development, FDA believes it is 
reasonable to consider WHO's ``neglected tropical disease'' 
designations in determining whether a disease should be designated as a

[[Page 50562]]

``tropical disease'' for purposes of section 524 of the FD&C Act.

III. Diseases Being Designated

    FDA has considered a number of diseases recommended in response to 
the Federal Register document announcing the December 12, 2008, public 
meeting (see 73 FR 66050, November 6, 2008), by meeting participants or 
others directing communications to FDA on the same topic. Based on an 
assessment using the criteria proposed previously, FDA has determined 
that the following diseases will be designated as ``tropical diseases'' 
under section 524 of the FD&C Act:
     Chagas disease.
     Neurocysticercosis.

FDA's rationale for adding these diseases to the list is discussed in 
the analyses that follow.

A. Chagas Disease

    Chagas disease, also known as American trypanosomiasis, is a 
vector-borne parasitic disease caused by the protozoan Trypanosoma 
cruzi (Ref. 16). After the initial infection, a 2-month ``acute'' phase 
occurs, during which there are some antiparasitic drugs that can be 
used for treatment in some patients (id.). Treatment efficacy generally 
decreases with length of infection, and if the disease is not cured 
during the initial ``acute'' infection phase, the chronic infection 
lingers over the next several years or decades, often causing organ and 
tissue damage (id.). For example, some Chagas disease sufferers who 
contract the disease during childhood die in early adulthood due to 
heart arrhythmias or other effects of organ damage. Efforts to reduce 
Chagas disease center around controlling the spread of the vector 
insects (e.g., through insecticide and roof repair) and protecting 
people from insect bites (e.g., through bed net use) (id.).
    Chagas disease has a disproportionate effect on poor and 
marginalized populations. Developing countries in Central and South 
America suffer most of the global DALYs lost because of the disease 
(id.). Estimates vary, but approximately 8 million people are believed 
to be infected in Mexico, Central America, and South America (Ref. 17). 
Within Chagas-endemic countries, the disease often affects rural and/or 
poor populations who live in the mud huts that also are inhabited by 
the vector insects (Ref. 16). WHO has designated Chagas as a neglected 
tropical disease (Ref. 15).
    There also is no significant market for Chagas disease treatment in 
developed nations. Based on estimates derived by applying published 
seroprevalence data to immigrant population estimates in the United 
States, it is estimated that there are just over 300,000 persons 
infected with T. cruzi in the United States (Refs. 17, 18, and 19). The 
number of persons with chronic cases for whom definitive 
recommendations for treatment would apply is likely less than 300,000. 
Transmission and acute cases of Chagas disease would be considered 
unlikely either in the United States or in other developed countries. 
The most common insect vector that transmits the parasite, the 
triatomine bug, is found mostly in Central and South America. The main 
risk of Chagas transmission to uninfected persons in developed 
countries is due to mother-to-child transmission, or blood transfusions 
or organ donations where the donor has lived in or visited Chagas-
endemic countries--although there have been a few reports of vector-
borne Chagas infecting people in the United States (Refs. 16 and 17).
    There are no approved vaccines or other preventative therapies for 
the disease, either in the United States or elsewhere. The only drugs 
used to treat Chagas are benznidazole and nifurtimox, which are not 
approved in the United States for this use. In addition to the lack of 
a commercial market in developed countries (presumably because of the 
low prevalence of disease), there does not seem to be a sizeable 
indirect (e.g., government) market for Chagas treatments either--
presumably because of the geographical limitations of the disease. As a 
general matter, Chagas-endemic countries are developing countries in 
Central and South America, and thus neither persons with Chagas disease 
nor their governments are likely to be in a position to provide a 
financial incentive for treatment development. Given the disease's 
geographical limitations and its prevalence in non-touristed rural 
areas, it is unlikely that the travelers' market would be a sufficient 
incentive to encourage treatment development for Chagas.
    Given the factors described in this document, FDA has determined 
that Chagas disease meets both statutory criteria of ``no significant 
market in developed nations'' and ``disproportionately affects poor and 
marginalized populations.'' Therefore, FDA is designating Chagas 
disease as a tropical disease under section 524 of the FD&C Act.

B. Neurocysticercosis

    Cysticercosis is a disease caused by infection with Taenia solium, 
a tapeworm of the phylum Platyhelminthes, and is contracted when a 
person ingests the tapeworm eggs. After a person ingests the eggs, the 
tapeworm enters the larval stage and begins to infect the host's 
tissues. The most severe form of the disease, called 
neurocysticercosis, occurs when larvae enter the central nervous system 
and establish cysts that can cause epilepsy (see, e.g., Ref. 20). 
Treatment guidelines from the American Academy of Neurology recommend 
treatment with anti-helminthic drugs like albendazole, with 
consideration for adjunctive corticosteroid therapy (Ref. 20).
    Neurocysticercosis disproportionately affects poor and marginalized 
populations. Indeed, patients who have infection with T. solium 
generally have similar socioeconomic and demographic characteristics to 
those patients with soil transmitted helminthiasis, a disease already 
on the statutory list of ``tropical diseases'' in section 524 of the 
FD&C Act. As of the late 1990s, approximately 50 million people 
worldwide were estimated to harbor the tapeworm T. solium (Ref. 21), 
most of them living in poverty in the world's poorest countries that 
lack effective systems for meat inspection and adequate sanitation 
(Refs. 22 and 23). Estimates of the number of people who have epilepsy 
caused by neurocysticercosis ranges from 450,000 to 1,350,000 in 
Central and South America and from 300,000 to 4,600,000 in sub-saharan 
Africa (Ref. 23). Neurocysticercosis is believed to contribute to high 
levels of human morbidity, notably epilepsy, though efforts are 
underway to adequately characterize an estimate of DALY for 
neurocysticercosis (Ref. 24). Notably, cysticercosis is included on 
WHO's list of neglected tropical diseases (Ref. 15).
    FDA also has determined that neurocysticercosis products have no 
significant market in developed nations. Although the disease does 
occur in the United States, estimates of annual incidence rates in the 
general U.S. population are low, at approximately 0.2 cases per 100,000 
population. Incidence rates are much higher among Hispanics living in 
the United States, who most likely acquired the tapeworm in 
cysticercosis-endemic areas of Central and South America (Ref. 25), 
with estimates ranging between 3.1 and 5.8 cases per 100,000 Hispanic 
population (Ref. 26). FDA also is unaware of evidence suggesting any 
sizeable military, government, or other indirect market for 
neurocysticercosis products.
    In view of the disease characteristics discussed previously, FDA 
considers the statutory criteria for addition of neurocysticercosis to 
the list of tropical

[[Page 50563]]

diseases in section 524 of the FD&C Act to be satisfied. This addition 
is effective upon the publication of this order.

IV. 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)(R) of the FD&C Act. By expanding the list with this order, 
FDA does not mean to preclude the future addition of other diseases to 
this list. To facilitate the consideration of future additions to the 
list, FDA is establishing a public docket (see http://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)(R) of the FD&C Act. FDA will periodically review these 
requests, and, when appropriate, expand the list.

V. Paperwork Reduction Act

    This final order establishes a 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)(R) of the FD&C Act. This 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.''

VI. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m. Monday through Friday, and 
are available electronically at http://www.regulations.gov.

    (FDA has verified the Web site addresses, but FDA is not 
responsible for any subsequent changes to the Web sites after this 
document publishes in the Federal Register.)

1. U.S. Food and Drug Administration, ``Guidance for Industry: 
Expedited Programs For Serious Conditions--Drugs and Biologics'' 
(available at http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf), 
2014.
2. IMF, ``World Economic Outlook: Recovery Strengthens, Remains 
Uneven,'' Table B1 (available at http://www.imf.org/external/pubs/ft/weo/2014/01/pdf/tblpartb.pdf).
3. U.N. Development Programme, ``Human Development Index (HDI)'' 
(available at http://hdr.undp.org/en/content/human-development-index-hdi).
4. The World Bank, ``Country and Lending Groups'' (available at 
http://data.worldbank.org/about/country-and-lending-groups).
5. U.N. Development Programme, ``Frequently Asked Questions--Human 
Development Index (HDI)'' (available at http://hdr.undp.org/en/faq-page/human-development-index-hdi#t292n36).
6. Congressional Research Service, ``Generalized System of 
Preferences: Background and Renewal Debate,'' pp. 7, 11 (available 
at http://fas.org/sgp/crs/misc/RL33663.pdf).
7. U.S. Department of Health and Human Services, ``Public Health 
Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation 
Plan,'' December 2012 (available at http://www.phe.gov/Preparedness/mcm/phemce/Documents/2012-PHEMCE-Implementation-Plan.pdf).
8. National Institute of Allergy and Infectious Diseases, NIAID 
Emerging Infectious Diseases/Pathogens (available at http://www.niaid.nih.gov/topics/biodefenserelated/biodefense/pages/cata.aspx).
9. Centers for Disease Control and Prevention, Bioterrorism Agents/
Diseases (available at http://www.bt.cdc.gov/agent/agentlist-category.asp).
10. Joint Program Executive Office for Chemical and Biological 
Defense, Joint Vaccine Acquisition Program (JVAP) (available at 
http://www.jpeocbd.osd.mil/packs/Default.aspx?pg=1208).
11. WHO, ``Metrics: Disability Adjusted Life Year (DALY)'' 
(available at http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/).
12. Medline Plus/Merriam-Webster Medical Dictionary Online, 
``Morbidity'' (available at http://www.merriam-webster.com/medlineplus/morbidity).
13. Merriam-Webster Dictionary Online, ``Marginalize'' (available at 
http://www.merriam-webster.com/dictionary/marginalize).
14. WHO, ``First WHO Report on Neglected Tropical Diseases: Working 
to Overcome the Global Impact of Neglected Tropical Diseases'' 
(available at http://whqlibdoc.who.int/publications/2010/9789241564090_eng.pdf).
15. WHO, ``Neglected Tropical Diseases: Diseases Covered by NTD 
Department'' (available at http://www.who.int/neglected_diseases/diseases/en/).
16. Centers for Disease Control and Prevention, ``Parasites--
American Trypanosomiasis (also known as Chagas Disease): Detailed 
FAQs'' (available at http://www.cdc.gov/parasites/chagas/gen_info/detailed.html).
17. Centers for Disease Control and Prevention, ``Parasites--
American Trypanosomiasis (also known as Chagas Disease): 
Epidemiology and Risk Factors,'' (available at http://www.cdc.gov/parasites/chagas/epi.html).
18. Bern, C. and S.P. Montgomery, ``An Estimate of the Burden of 
Chagas Disease in the United States,'' Clinical Infectious Diseases, 
49:e52-54, 2009 (available at http://cid.oxfordjournals.org/content/49/5/e52.full).
19. Centers for Disease Control and Prevention, ``Congenital 
Transmission of Chagas Disease--Virginia, 2010,'' MMWR. Morbidity 
and Mortality Weekly Report, 61(26):477-479, July 6, 2012 (available 
at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6126a1.htm?s_cid=mm6126a1_w).
20. Baird, R.A., S. Weibe, J.R. Zunt, et al., ``Evidence-Based 
Guideline: Treatment of Parenchymal Neurocysticercosis,'' Neurology, 
80:1424-1429, 2013 (available at http://www.neurology.org/content/80/15/1424.full.pdf).
21. White, A.C., Jr., ``Neurcysticercosis: A Major Cause of 
Neurological Disease Worldwide,'' Clinical Infectious Disease, 
24:101-115, 1997 (available at http://cid.oxfordjournals.org/content/24/2/101.long).
22. Institute of Medicine, ``The Causes and Impacts of Neglected 
Tropical and Zoonotic Diseases: Opportunities for Integrated 
Intervention Strategies,'' Washington, DC: The National Academies 
Press (available at http://www.ncbi.nlm.nih.gov/books/NBK62507/pdf/TOC.pdf).
23. Mewara, A., K. Goyal, and R. Sehgal, ``Neurocysticercosis: A 
Disease of Neglect,'' Tropical Parasitology, 3(2):106-113, 2013 
(available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889086/?report=printable).
24. Bhattarai, R., H. Carabin, and C. Budke, ``The Burden of 
Cysticercosis,'' Novel Aspects on Cysticercosis and 
Neurocysticercosis, H.F. Sibat, ed. (available at http://www.intechopen.com/books/novel-aspects-on-cysticercosis-and-neurocysticercosis/the-burden-of-cysticercosis).
25. Wallin, M.T. and J.F. Kurtzke, ``Neurocysticercosis in the 
United States: Review of an Important Emerging Infection,'' 
Neurology, 63:1559-1564, 2004 (available at http://www.neurology.org/content/63/9/1559.long).
26. O'Neal, S., J. Noh, P. Wilkins, et al, ``Taenia solium Tapeworm 
Infection, Oregon, 2006-2009,'' Emerging Infectious Disease, 
17(6):1030-1036, 2011 (available at http://wwwnc.cdc.gov/eid/article/17/6/10-1397_article).

[[Page 50564]]

    Dated: August 14, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-20554 Filed 8-19-15; 8:45 am]
 BILLING CODE 4164-01-P