Guidance for Industry 

Tropical Disease Priority 

Review Vouchers 

DRAFT GUIDANCE
 

This guidance document is being distributed for comment purposes only. 

Comments and suggestions regarding this draft document should be submitted within 60 days of 

publication in the Federal Register of the notice announcing the availability of the draft 

guidance. Submit comments 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 listed in the notice of availability that publishes in 

the Federal Register. 

For questions regarding this draft document contact David Roeder (CDER), 301-796-0799, or 

the Office of Communications, Training, and Manufacturers Assistance (CBER), 301-827-1800 

or 800-835-4709. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

October 2008 

Procedural 
 

 

 

Guidance for Industry 

Tropical Disease Priority 

Review Vouchers 

Additional copies are available from: 

Office of Training and Communications
 

Division of Drug Information, HFD-240
 

Center for Drug Evaluation and Research
 

Food and Drug Administration 

10903 New Hampshire Avenue 

Silver Spring, MD 20993
 

Phone: 301-796-3400; Fax: 301-847-8714 

druginfo@fda.hhs.gov 

http://www.fda.gov/cder/guidance/index.htm
 

and/or 

Office of Communication, Training, and Manufacturers Assistance, HFM-40
 

Center for Biologics Evaluation and Research 

Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1488 

http://www.fda.gov/cber/guidelines.htm
 

(tel) 800-835-4709 or 301-827-1800 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

October 2008 

Procedural 
TABLE OF CONTENTS 

I. INTRODUCTION............................................................................................................. 1
 

II. BACKGROUND ............................................................................................................... 1
 

III. PROVISIONS OF SECTION 524 – AN OVERVIEW.................................................. 2
 

IV. POLICIES AND PROCEDURES – QUESTIONS AND ANSWERS ......................... 2
 
 

 

Contains Nonbinding Recommendations 

Draft — Not for Implementation 

1 Guidance for Industry1
 

2 Tropical Disease Priority Review Vouchers 

3 

4 

5 

6 This draft guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s) current 

7 thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 

8 bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 

9 the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA 

10 staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 

11 the appropriate number listed on the title page of this guidance. 

12 

13 

14 

15 I. INTRODUCTION 

16 

17 This guidance provides information on the implementation of section 1102 of the Food and Drug 

18 Administration Amendments Act of 2007 (FDAAA), which adds new section 524 to the Federal 

19 Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 360n). Section 524 authorizes FDA to 

20 award priority review vouchers to sponsors of certain tropical disease product applications that 

21 meet the criteria specified by the Act. A priority review voucher may be used by the sponsor 

22 who obtains it or another sponsor to obtain a priority review for a different application. A 

23 priority review voucher may be transferred from the sponsor who obtains it to another sponsor. 

24 

25 FDA’s guidance documents, including this guidance, do not establish legally enforceable 

26 responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should 

27 be viewed only as recommendations, unless specific regulatory or statutory requirements are 

28 cited. The use of the word should in Agency guidances means that something is suggested or 

29 recommended, but not required. 

30 

31 

32 II. BACKGROUND 

33 

34 Section 524 is designed to encourage development of new drug and biological products for 

35 prevention and treatment of certain tropical diseases affecting millions of people throughout the 

36 world. While diseases addressed by this legislation represent an important disease burden for 

37 humanity, there has been remarkably little progress over the past 50 years in development of 

38 drugs for these diseases. Because these diseases are found primarily in poor and developing 

39 countries, existing incentives have been insufficient to encourage development of new and 

40 innovative drug therapies. Although these tropical diseases are rare in the United States, 

41 intercontinental jet transport, immigration, tourism, and military operations are increasing the 

42 direct impact these diseases have on the health of Americans. By enacting section 524, Congress 

1

 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for 

Biologics Evaluation and Research (CBER) at the Food and Drug Administration. 
Contains Nonbinding Recommendations 

Draft — Not for Implementation 

43 is attempting to stimulate new drug development by offering additional incentives for obtaining 

44 FDA approval of certain tropical disease drug products. Under section 524, the sponsor of a 

45 human drug application for a qualified tropical disease may be eligible for a voucher that can be 

46 used to obtain a priority review for any subsequent human drug application under section 

47 505(b)(1) of the Act or section 351 of the Public Health Service (PHS) Act. 

48 

49 III. PROVISIONS OF SECTION 524 – AN OVERVIEW 

50 

51 A. What applications are eligible to receive a tropical disease priority review voucher? 

52 

53 • The application must be for a listed tropical disease (see section IV, Question 2 of 

54 this guidance). 

55 • The application must be submitted under section 505(b)(1) of the Act or section 351 

56 of the PHS Act. 

57 • The drug that is the subject of the application must contain no active ingredient 

58 (including any ester or salt of the active ingredient) that has been approved in any 

59 other application under section 505(b)(1) the Act or section 351 of the PHS Act. 

60 • The application must be submitted after the enactment of FDAAA (September 27, 

61 2007). 

62 • The application must qualify for a priority review. 

63 

64 B. What are the parameters for use of a tropical disease priority review voucher? 

65 

66 • The voucher cannot be issued until at least 1 year after September 27, 2007, the date 

67 of FDAAA enactment. 

68 • The application using the priority review voucher must also be a 505(b)(1) or section 

69 351 PHS Act application, and is not limited to products for tropical diseases. 

70 • At least 1 year in advance, the sponsor planning to use the voucher must notify FDA 

71 of intent to use the voucher and the date on which the sponsor intends to submit the 

72 application. 

73 • A sponsor using the voucher must pay an extra user fee to support the review of the 

74 application based on the average cost of a priority NDA/BLA review in the previous 

75 fiscal year. Payment of this extra fee, to which the sponsor is legally committed as a 

76 result of the notification of its intent to use the voucher, is not subject to waivers, 

77 exemptions, reductions, or refunds. 

78 • The sponsor of a tropical disease product receiving a priority review voucher may 

79 transfer the voucher to another sponsor (see section IV, Question 8) 

80 

81 IV. POLICIES AND PROCEDURES – QUESTIONS AND ANSWERS 

82 

83 Since the enactment of FDAAA, the Agency has received numerous inquiries about the scope of 

84 section 524 and how various aspects of section 524 should be interpreted. The purpose of this 

85 guidance is to provide a response to these questions. 

86 

87 

88 

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89 Q1. What is a tropical disease product application? 

90 

91 The term tropical disease product application is defined in section 524(a)(4) of the Act. The 

92 term refers to an application that — 

93 

94 • is a human drug application as defined in section 735(1) of the Act2— 

95 o for prevention or treatment of a tropical disease; and 

96 o the FDA deems eligible for priority review; 

97 • is approved after the date of the enactment of FDAAA by the FDA for use in the 

98 prevention or treatment of a tropical disease; and 

99 • is for a human drug, no active ingredient (including any ester or salt of the active 

100 ingredient) of which has been approved in any other application under section 505(b)(1) 

101 of the Act or section 351 of the PHS Act. 

102 

103 Q2. What tropical disease product applications may qualify for a priority review 

104 voucher? 

105 

106 Product applications for the prevention or treatment of the following tropical diseases may 

107 qualify: 

108 

109 • Tuberculosis 

110 • Malaria 

111 • Blinding trachoma 

112 • Buruli Ulcer 

113 • Cholera 

114 • Dengue/Dengue haemorrhagic fever 

115 • Dracunculiasis (guinea-worm disease) 

116 • Fascioliasis 

117 • Human African trypanosomiasis 

118 • Leishmaniasis 

119 • Leprosy 

120 • Lymphatic filariasis 

121 • Onchocerciasis 

122 • Schistosomiasis 

123 • Soil transmitted helminthiasis 

124 • Yaws 

125 • Any other infectious disease for which there is no significant market in developed nations 

126 and that disproportionately affects poor and marginalized populations, designated by 

127 regulation by the Secretary (section 524(a)(3)) 

128 

129 

2

 This definition includes drugs and most biological drugs, excluding blood components and certain other biological 

drug products. For details, refer to section 735(1) of the Act (21 U.S.C. 379g(1)). The definition does not cover 

medical devices. 

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130 Q3. What user fees apply to a tropical disease application? 

131 

132 User fees for human drug applications are described in sections 735 and 736 of the Act.3 In 

133 general, a tropical disease application would be subject to these statutory requirements like any 

134 other application. However, we anticipate that many tropical disease applications may qualify 

135 for designation as orphan drug products. Under section 736(a)(1)(F) of the Act, if a human drug 

136 application for a prescription drug product that has been designated as a drug for a rare disease or 

137 condition under section 526 of the Act, the application is not subject to an application user fee, 

138 unless the application includes an indication for other than a rare disease or condition. In 

139 addition, section 736(k) of the Act provides for an exemption from annual product and 

140 establishment fees for certain orphan designated drugs. 

141 

142 Q4. What is a priority review? 

143 

144 A priority review is a review conducted with a PDUFA goal date of 6 months. Normally, an 

145 application for a CDER product will qualify for a priority review if FDA determines that the 

146 product, if approved, would provide safe and effective therapy where no satisfactory alternative 

147 therapy exists or would be a significant improvement compared to marketed products, including 

148 non-drug products and/or therapies, in the treatment, diagnosis, or prevention of a disease. See 

149 CDER’s Manual of Policies and Procedures (MAPP) 6020.3, “Review Classification Policy: 

150 Priority and Standard.”4 A CBER product will qualify for a priority review if FDA determines 

151 that the product, if approved, would be a significant improvement in the safety or effectiveness 

152 of the treatment, diagnosis, or prevention of a serious or life-threatening disease. 

153 

154 FDA has committed to a goal to review and act on 90 percent of the applications that have been 

155 granted priority review status no later than 6 months after receipt, as described in the CDER 

156 MAPP and goals identified in the letters described in section 101(c) of the FDAAA.5 An 

157 application that does not receive a priority designation will receive a “standard” review. Under 

158 the goals referenced in FDAAA section 101(c), FDA commits to a goal to review and act on 90 

159 percent of “standard” applications within 10 months of the date of receipt. Please note that an 

160 FDA review within a specific time frame does not mean an application will be approved within 

161 that time frame. The term “review and act on” is understood to mean the issuance of an approval 

162 or complete response letter after the review of a filed application. The action letter, if it is not an 

163 approval, will set forth in detail the specific deficiencies that need to be addressed before the 

164 application can be approved. 

165 

166 Q5. What is a priority review voucher and when is it awarded? 

167 

168 The term priority review voucher is defined in section 524(a)(2) of the Act. It refers to a voucher 

169 issued by the Secretary to the sponsor of a tropical disease product application at the time of 

3

 21 U.S.C. 379g and 379h. 

4

 Available on the Internet at http://www.fda.gov/cder/mapp.htm. 5

 See letters from the Secretary of Health and Human Services to the Chairman of the Committee on Health, 

Education, Labor, and Pensions of the Senate and the Chairman of the Committee on Energy and Commerce of the
 

House of Representatives, as set forth in the Congressional Record, available on the Internet at 

http://www.fda.gov/oc/pdufa4/pdufa4ltr.pdf. 

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170 approval of the application that entitles the holder of such voucher to designate a single human 

171 drug application submitted under section 505(b)(1) or section 351 of the PHS Act (see section 

172 524(a)(2) of the Act) as qualifying for a priority review. Such a subsequent application would 

173 not have to meet the usual requirements for a priority review. (See Q13.) 

174 

175 Q6. Would eligibility to receive a priority review voucher be affected in any way by 

176 whether the sponsor intends to market or distribute the qualifying tropical disease 

177 product after approval? 

178 No, it does not matter if the sponsor decides not to market the product. Eligibility will be based 

179 on the criteria outlined in the statute. 

180 

181 Q7. What form will the voucher take? 

182 

183 The FDA will include information related to the priority review voucher in the approval letter for 

184 the tropical disease drug application. 

185 

186 Q8. Will these vouchers be transferable? 

187 

188 Yes, by the sponsor receiving the voucher. As the statute states (section 524(b)(2)), the tropical 

189 disease product sponsor receiving a tropical disease priority review voucher may transfer the 

190 entitlement to such voucher (including by sale) to another sponsor of a human drug application. 

191 The language of the statute allows for one transfer from the original recipient of the voucher to 

192 another sponsor of a human drug for which an application under section 505(b)(1) of the Act or 

193 section 351 of the PHS Act will be submitted after the date of the approval of the tropical disease 

194 product application. Although the statute’s language imposes a limitation of one actual transfer 

195 of the voucher, FDA believes that contractual arrangements such as the use of an option or 

196 transfer of the right to designate the voucher’s recipient could comply with the terms of the 

197 statute. 

198 

199 Q9. What is the procedure for voucher transfer? 

200 

201 The transfer should be documented with a letter of transfer from the tropical disease application 

202 holder granted the voucher and a letter from the new voucher owner acknowledging the transfer. 

203 These letters should be included in the application for which the sponsor wishes to redeem the 

204 priority review voucher. A voucher cannot be redeemed unless a complete record of transfer is 

205 available to the Agency. 

206 

207 Q10. When can a voucher be used? 

208 

209 After the voucher is issued, the sponsor redeeming the voucher must notify FDA of their intent 

210 to submit a human drug application with a priority review voucher at least 365 days prior to 

211 submission of the human drug application for which a priority review voucher will be used to 

212 obtain a priority review. The notification must include the date the sponsor intends to submit the 

213 application. In accordance with the language of the statute, FDA will consider this notification 

214 as a legally binding commitment to pay the priority review user fee for the fiscal year in which 

215 the application is submitted. 

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216 

217 

218 Q11. What fees apply when using a priority review voucher? 

219 

220 The sponsor of a human drug application that is the subject of a priority review voucher must 

221 pay FDA a priority review user fee in addition to any other fee required under the prescription 

222 drug user fee program. As the statute requires, the amount of the priority review user fee will be 

223 determined each fiscal year and based on the average cost incurred by FDA in the review of a 

224 human drug application subject to priority review in the previous fiscal year. 

225 

226 FDA will establish the fee amount before the beginning of each fiscal year and will publish the 

227 fee schedule in the Federal Register. 

228 

229 Q12. When do I pay the priority review voucher fee? 

230 

231 According to the terms of the statute, the priority review user fee is due upon submission of the 

232 application for which the priority review voucher is used. The statute specifies that the 

233 application will be considered incomplete if the priority fee and all other applicable user fees are 

234 not paid in accordance with FDA payment procedures. In addition, FDA cannot collect these 

235 fees in any fiscal year until Congress has passed a law appropriating funds for these fees. 

236 Because FDA may not grant a waiver, exemption, reduction, or refund of any fees due and 

237 payable under this section of the Act and FDA may not collect priority review voucher fees prior 

238 to a relevant appropriation for that fiscal year, FDA cannot accept any application using a 

239 priority review voucher if the necessary appropriation has not become law for that fiscal year. 

240 

241 Q13. If I present a voucher to FDA for priority review, am I guaranteed a 6-month 

242 review on my new drug application? 

243 

244 No. The definition of priority review in section 524(a)(1) refers to the CDER MAPP and the 

245 PDUFA goals letter.6

 We believe the intent of this section is that drugs for which priority review 

246 vouchers are used should be treated as if they were any other priority review drug. Therefore, 

247 these applications would be placed in the priority review group. The Agency has committed to a 

248 goal of completing 90 percent of priority reviews within 6 months. 

249 

250 Q14. Can FDA determine whether an application will be eligible to receive a voucher 

251 before an application is approved or licensed (i.e., prior to NDA/BLA submission or 

252 during review of the application)? 

253 

254 No. It is important to note that a product that meets the criteria at the time of submission may 

255 not meet those same criteria at the time of the approval action and would thus not be eligible to 

256 receive a priority review voucher. This could occur if another application containing the same 

257 active ingredient is approved first. For this reason, the Agency will not make voucher 

258 determinations until the time of application approval. 

259 

260 Q15. Are combination products eligible for priority review vouchers? 

6

 The PDUFA goals can be found on the Internet at http://www.fda.gov/oc/pdufa4/pdufa4goals.html. 

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261 

262 It depends. A combination product is eligible if the product, including all active ingredients, 

263 meets the criteria established in FDAAA. However, if the product contains any active ingredient 

264 that has been previously approved, the application is not eligible for a priority voucher (see 

265 section 524(a)(4)(C) of the Act). 

266 

267 Q16. Are products eligible that have been approved and used in other countries but have 

268 not previously been submitted for review by the FDA? 

269 

270 Yes, as long as they meet all the elements for a tropical disease product application described in 

271 section 524(a)(4). 

272 

273 Q17. Is a drug that is already approved for another indication eligible for a priority 

274 review voucher for a tropical disease application? 

275 

276 No. For an application to qualify, it must be for a human drug, no active ingredient (including 

277 any ester or salt of the active ingredient) of which has been approved in any other application 

278 under section 505(b)(1) of the Act or section 351 of the PHS Act. 

279 

280 Q18. Would a new pediatric formulation for a drug already approved for adults be 

281 eligible? 

282 

283 No. As noted above, an application for a product containing a previously approved drug is not 

284 eligible to receive a tropical disease priority voucher. 

285 

286 Q19. Would an application for a tropical disease product submitted to FDA prior to 

287 enactment of the statute but not yet approved qualify for a voucher? 

288 

289 No. The tropical disease product sponsor may not receive a tropical disease priority voucher if 

290 the application was submitted to the FDA before the date of the enactment of section 524 

291 (September 27, 2007). 

292 

293 Q20. Through what mechanism should a sponsor notify FDA that it intends to submit an 

294 application eligible to receive a voucher? 

295 

296 The original submission of the tropical disease application should include the sponsor’s request 

297 outlining how they meet the eligibility criteria for a priority review voucher. We encourage early 

298 communication with the review division in which these issues could be discussed; however, 

299 notification before submission of the tropical disease application is not required. 

300 

301 Q21. Could a tropical disease product also qualify as an orphan drug? 

302 

303 It is likely that a drug product meeting the requirements of section 524 will also qualify for 

304 marketing exclusivity, tax credits, fee exemptions, and orphan product grants provided under the 

305 Orphan Drug Act. For information regarding these incentives, potential sponsors should contact 

306 the Office of Orphan Products Development (OOPD). These products may also qualify for new 

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Draft — Not for Implementation 

307 chemical entity marketing exclusivity provided under the Act. For information regarding new 

308 chemical entity marketing exclusivity, potential sponsors should contact the appropriate CDER 

309 review division. 

310 

311 Q22. What are the different roles played by CDER, CBER, and the Office of Orphan 

312 Products Development? 

313 

314 CDER and CBER 

315 

316 The review divisions within the Center for Drug Evaluation and Research and the Center for 

317 Biologics Evaluation and Research have the responsibility for premarket review of the tropical 

318 disease product applications and for determining whether an application meets the eligibility 

319 criteria for receiving a priority review voucher. 

320 

321 Office of Orphan Products Development 

322 

323 The Office of Orphan Products Development is located within the Office of the Commissioner 

324 and is responsible for determining whether a drug or biologic qualifies for orphan drug status. 

325 For example, to secure orphan status for the treatment of a rare disease, a sponsor demonstrates 

326 to OOPD that the disease or condition is rare in the United States (i.e., <200,000 persons in the 

327 United States are currently affected) and that the drug is expected to be effective (i.e., is 

328 promising) in the treatment of the disease. Orphan-drug designation must be granted prior to the 

329 submission of a marketing application. This is a separate process from the determination of 

330 whether a drug or biologic will qualify as a tropical disease drug or will ultimately be eligible for 

331 a voucher under the provisions of section 524. The latter determination will be made by CDER 

332 or CBER, as appropriate. 

333 

334 If the product meets the criteria of the Orphan Drug Act, OOPD will provide orphan designation 

335 that qualifies the sponsor of the product for a tax credit and the marketing incentives of the 

336 Orphan Drug Act.7

 Questions concerning orphan drug designations, or the benefits and 

337 requirements associated with such designations, should be directed to OODP 

338 (http://www.fda.gov/orphan). 

339 

340 Q23. Does FDA plan to add other infectious diseases to the list? If so, when can we expect 

341 to see that? 

342 

343 Section 524 allows FDA to designate by regulation any other infectious disease for which there 

344 is no significant market in developed nations and that disproportionately affects poor and 

345 marginalized populations. FDA intends to seek public input regarding the criteria that could be 

346 used to designate other diseases as well as specific diseases that might meet those criteria. 

347 

348 Q24. What should I do if I have other questions about a tropical disease application? 

349 

350 Sponsors with questions not addressed in this guidance should contact the appropriate review 

351 division within the Center for Drug Evaluation and Research (CDER) or Center for Biologics 

7

 Information on the Orphan Drug Act is available at http://www.fda.gov/orphan/progovw.htm. 

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352 Evaluation and Research (CBER). CDER and CBER encourage early interaction with potential 

353 sponsors so these types of questions can be discussed. Such interactions could begin as early as 

354 the pre-IND phase of drug development. 

355 

9