The US Food and Drug Administration (FDA), authorized by the Federal Food, Drug and Cosmetic Act (FD&C Act), section 524, may award priority review vouchers (PRVs) to sponsors of approved tropical disease product applications that meet certain criteria.
The FDA finalized a guidance providing information on the implementation of section 524 of the FD&C Act – Tropical Disease Priority Review Vouchers Guidance for Industry in October 2016. To qualify for a PRV, a sponsor’s application must be for a drug or biological product for the prevention or treatment of a “tropical disease,” must otherwise qualify for priority review, and must contain no active ingredient (including any salt or ester of an active ingredient) that has been approved in any other application under section 505(b)(1) of the FD&C Act or section 351 of the Public Health Services Act.
The FDA Reauthorization Act of 2017 made changes to the eligibility criteria for receipt of a tropical disease priority review voucher. Applications submitted after September 30, 2017 must also contain reports of one or more new clinical investigations (other than bioavailability studies) that are essential to the approval of the application and conducted or sponsored by the sponsor. In addition, the applicant must provide in the application an attestation that such report(s) were not submitted as part of an application for marketing approval or licensure by a regulatory authority in India, Brazil, Thailand, or any country that is a member of the Pharmaceutical Inspection Convention or the Pharmaceutical Inspection Cooperation Scheme prior to September 27, 2007.
Once the sponsor obtains a PRV, the voucher can be used to obtain priority review designation for a subsequent application that does not itself qualify for priority review as described in the guidance. The following list includes all diseases qualifying for a tropical disease PRV, including those initially specified in section 524, those added by subsequent legislation, and those the FDA has added by order under 524(a)(3)(S):
· Tuberculosis
· Malaria
· Blinding trachoma
· Buruli ulcer
· Cholera
· Dengue/Dengue hemorrhagic fever
· Dracunculiasis (guinea-worm disease)
· Fascioliasis
· Human African trypanosomiasis
· Leishmaniasis
· Leprosy
· Lymphatic filariasis
· Onchocerciasis
· Schistosomiasis
· Soil transmitted helminthiasis
· Yaws
· Filovirus Diseases (added December 16, 2014 by Pub. L. 113-233, amended by Pub. L. 114-146)
· Zika Virus Disease (added April 19, 2016 by Pub. L. 114-146)
Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations, designated by order of the Secretary:
· Chagas disease (August 20, 2015 final order)
· Neurocysticercosis (August 20, 2015 final order)
· Chikungunya Virus Disease (August 24, 2018 final order)
· Lassa Fever (August 24, 2018 final order)
· Rabies (August 24, 2018 final order)
· Cryptococcal Meningitis (August 24, 2018 final order)
An application awarded a tropical disease PRV must be for the “prevention or treatment of a tropical disease” as listed and described in the statute. Section 524(a)(3) of the FD&C Act established a list of tropical diseases qualifying for a PRV and included a provision that additional diseases could be designated by the Secretary. The authority to designate additional diseases, like most other authorities under the FD&C Act, has been delegated to the FDA.
The FDA opened a public docket (FDA-2008-N-0567-0011), to which interested parties can submit:
· Additional disease candidates for designation under section 524(a)(3)(S)
· Supporting materials documenting why the candidate disease meets the statutory criteria for designation
Section 524 does not provide a time period for designation, nor does it establish any designation or disease candidate submission process, other than to specify that the designation must be “by order of the Secretary.” The FDA’s docket review process is described below.
To evaluate additional disease candidates submitted to the docket for designation, the FDA is reviewing submissions to the docket on an ongoing basis. The FDA intends to publish in the Federal Register (FR) four times per year:
· A final order listing any disease that the FDA has determined meets the statutory standard for a “tropical disease” (if at least one of the diseases under consideration for the relevant time period under review meets the statutory criteria at that time), and/or
· A notice explaining which disease(s) the FDA believes do(es) not meet the statutory standard for a “tropical disease” (if at least one of the diseases does not meet the criteria based on currently available information)
The August 20, 2015, final order described the submission process and FDA’s interpretation of the designation criteria. Publication of the next order and/or notice is targeted for the first half of 2017, addressing docket submissions received between August 20, 2015 and June 30, 2016. Those stakeholders who suggested diseases to the agency via any route prior to August 20, 2015 should resubmit their suggested diseases if they wish the FDA to further consider these disease candidates.
Submitters may include expanded or updated supportive information to assist the FDA evaluation.
Thereafter, beginning with the three-month interval ending September 30, 2016, subsequent docket cohorts will be batched in three-month intervals. The FDA’s goal for responding to subsequent cohorts with an FR notice and/or order is nine months from the end of that particular docket period.
The FDA encourages those who suggest additional diseases for designation to include in their submission sufficient information to document that the disease meets the criteria set forth in section 524(a)(3)(S) (“any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations, designated by order of the Secretary”).
The agency explained its interpretation of these terms, including the criteria it will consider in evaluating whether these terms have been met, in the August 20, 2015, order. The agency encourages interested parties to review this order and recommends that docket submissions include supporting reference materials and information that address how the criteria described in the order are met.
When sponsors use a priority review voucher to obtain a priority review of a drug application, they are required to pay a fee in order to do so. This fee is independent of any other user fees that may be required. The fee for using a tropical disease PRV is set in a Federal Register notice published annually.
