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安渡生物医学写作总监
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1982年取得西班牙巴塞罗那大学药学院药理学博士，1994年取得巴塞罗那大学制药科学MBA
Rare Pediatric Disease Priority Review Vouchers Summary I. INTRODUCTION This guidance, issued July 2019, provides information on the implementation of section 908 of the Food and Drug Administration Safety and Innovation Act (FDASIA) which added section 529 to the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Under section 529, FDA will award priority review vouchers to sponsors of certain rare pediatric disease product applications that meet the criteria specified in that section. II. BACKGROUND AND OVERVIEW
The Advancing Hope Act of 2016 updated the definition of "rare pediatric disease" and created a requirement for sponsors seeking a rare pediatric disease priority review voucher to request the voucher upon submission of the rare pediatric disease product application.
This guidance is intended to assist developers of rare pediatric disease products in assessing whether their product may be eligible for rare pediatric disease designation and a rare pediatric disease priority review voucher.
It also clarifies the process for requesting such designations and vouchers, sponsor responsibilities upon approval of a rare pediatric disease product application, and the parameters for using and transferring a rare pediatric disease priority review voucher.
III. DEFINITIONS, POLICIES AND PROCEDURES. QUESTIONS AND ANSWERSA. Rare Pediatric Disease Product Applications
Q1. What is a "rare pediatric disease"?
A "rare pediatric disease" as a disease that meets each of the following criteria:
(A) The disease is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents [; and] (B) The disease is a rare disease or condition.
Serious or life-threatening manifestations primarily affect children
This guidance uses the term “children” to mean the definition of the pediatric population as individuals aged from birth to 18 years. The FDA interprets the current definition of "rare pediatric disease" and its reference to "serious or life-threatening manifestations of the disease or condition" using the following principles:
A manifestation of the disease or condition should be serious or life-threatening in children aged 0 through 18 years of age. Manifestations include expressions and symptoms of the disease or condition. Note that “manifestations” does not mean the onset of the disease or condition or the onset of treatment.
If treatment for the disease or condition begins in childhood, but under current standard of care the manifestations of the disease or condition are not serious or life-threatening in children, the disease or condition is not a rare pediatric disease.
FDA will consider the manifestations of the disease or condition in the context of standard of care for the disease or condition. Specifically, FDA will consider what manifestations of the disease or condition are serious or life-threatening in children under standard treatment for the disease or condition. Therefore, FDA will not consider the serious or life-threatening manifestations of the disease or condition that only occur when the disease is left untreated if that is not the standard of care.
FDA will assess the serious or life-threatening manifestations of the disease or condition and determine which manifestations primarily affect children and which primarily affect adults. Factors in determining if a manifestation primarily affects children include timing and rate of disease progression and whether the proportion of children is greater than the proportion of adults with the given manifestation. If the disease or condition has a manifestation that primarily affects children, FDA will consider the disease or condition to be a rare pediatric disease.
The serious and life-threatening manifestations of the disease or condition that primarily affect children will also be a factor in determining whether the application qualifies for a voucher.
Rare disease or condition
A "rare disease or condition" as any disease or condition that affects less than 200,000 persons in the United States (U.S.) or affects more than 200,000 in the U.S. and for which there is no reasonable expectation that the cost of developing and making available in the U.S. a drug for such disease or condition will be recovered from sales in the U.S. of such drug.
A drug may also meet the "rare disease or condition" requirement if it is for an "orphan subset" of a disease or condition that otherwise affects 200,000 or more persons in the U.S. In order for such drug to qualify as a drug for a "rare pediatric disease," the orphan subset must be serious or life-threatening and the serious or life-threatening manifestations of the orphan subset must primarily affect individuals aged from birth to 18 years.
The calculation of prevalence estimates will depend on whether the drug is a therapeutic drug or a vaccine, diagnostic drug, or preventive drug, as follows:
For therapeutic drugs, prevalence estimates of the entire affected U.S. population should be based on the number of individuals diagnosed with the disease or condition. For some diseases and conditions, individuals may have an underlying genetic abnormality at birth but may not develop manifestations of the disease until later, if ever. In these instances, whether individuals are considered “diagnosed” for the purpose of estimating prevalence may depend on whether the product is intended to treat an underlying genetic abnormality, attenuate or prevent progression of the clinical expression of the disease, or treat the clinical symptoms or manifestations of the disease.
For vaccines, diagnostic drugs, and preventive drugs, prevalence estimates should be based on the number of persons of all ages to whom the drug will be administered in the U.S. annually.
Qualifying as a drug for a "rare pediatric disease" is not sufficient to receive a priority review voucher. For sponsors to receive such a voucher, the application for the drug must meet all of the remaining eligibility criteria described in response to Question 2 (below).
Q2. What is a "rare pediatric disease product application"?
The term rare pediatric disease product application is defined in section 529(a)(4) of the FD&C Act. It refers to an application that:
Is a human drug application that contains no active ingredient previously approved
That FDA deems eligible for priority review
Is submitted under section 505(b)(1) of the FD&C Act or section 351(a) of the Public Health Service Act
Relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population
Does not seek approval for an adult indication in the original rare pediatric disease product application
Is approved after the date of enactment of the Advancing Hope Act of September 30, 2016
Q3. What does it mean to be "for" prevention or treatment of a rare pediatric disease?
To be eligible for a voucher, the drug should be either approved for a rare pediatric disease and or to treat or prevent a serious or life-threatening manifestation of the disease or condition that affects children. These serious or life-threatening manifestations may be the manifestations that primarily affect children, but they are not required to be, so long as the approved indication is clinically meaningful to pediatric patients with the disease or condition. For example:
A drug may meet this standard if the approved indication is explicitly for treatment or prevention of a serious or life-threatening manifestation of the disease or condition that affects children.
A drug may also meet this standard if the drug treats or prevents the underlying cause of the disease or condition and the approved indication is for treatment or prevention of the disease or condition generally.
FDA will look at the totality of the evidence to determine if the approval is clinically meaningful for the serious or life-threatening manifestations of the disease that affect children.
FDA encourages sponsors to work with the relevant review division or office in CBER or CDER to ensure they are studying the drug in a way that establishes safety and efficacy for the drug "for" a rare pediatric disease.
The priority review voucher request should include scientific justification of how the approved indication will be clinically meaningful to pediatric patients with the disease or condition with a written description of the data and endpoints from the submitted studies that supports a determination that the drug is for pediatric patients with the rare pediatric disease as described above.
Q4. What does "relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population" mean?
We interpret “relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population” to mean that, to be eligible for a voucher, the approved product:
Should have been studied in a clinically meaningful pediatric population with the rare disease (although the studies may also include adults in appropriate circumstances), and
The pediatric data should have been critical to obtaining adequate labeling for the pediatric population in terms of safety, effectiveness, and dosage information
It is important that applicants seeking a voucher submit data adequate for labeling the drug for use by the full range of affected pediatric patients, within reasonable limits.
The studied pediatric population should be clinically meaningful and represent more than a token pediatric population. Such labeling aligns with the intent of section 529, which is to help address the unmet medical needs of pediatric patients with rare pediatric diseases.
Sponsors are not required to study a manifestation of the disease or condition that primarily affects pediatric patients, but the studies should support approval for a rare pediatric disease in a way that is clinically meaningful to pediatric patients with the disease or condition.
Q5. What does "Does not seek approval for an adult indication in the original rare pediatric disease product application" mean?
The applicant cannot seek approval for a different adult indication or for a different disease or condition in the original rare pediatric disease application.
If the applicant seeks approval for use by pediatric and adult populations with the rare pediatric disease, the applicant will still be eligible for a voucher if the approved use includes pediatric use.
If the applicant obtains approval for use only in an adult population with the rare pediatric disease, the applicant is ineligible for a voucher.
An applicant can preserve voucher eligibility even if the applicant seeks approval for use by adults in addition to pediatric patients with the rare pediatric disease.
Clinical Trial Design – Clinical Trials for a Potential Rare Pediatric Disease Product May Need to Include Individuals Over 18 Years of Age for Scientific or Ethical Reasons:
Clinical trials for rare diseases will attempt to include all patients with the rare disease or condition that are available for study and who could reasonably be expected to benefit from the intervention, regardless of the age of the patient.
Studies using novel therapies should generally be conducted in young adults (18 to 21 years of age) prior to exposing adolescents and younger pediatric patients; for children to be included in early phase investigations, there must be a prospect of direct benefit for an individual child to be studied in a clinical trial.
Data to Include in a Marketing Application – Available Adult Safety and Effectiveness Data Must be Included in the Application:
If clinical safety and effectiveness data are available in an adult at the time of the submission of an original application for a potential rare pediatric disease product, these data must be included in the application for FDA’s review.
If there is a population over 18 years of age with the rare pediatric disease that could benefit from the product and for whom there are available data to support the evaluation of the safety and effectiveness of the product, labeling for such a population should be sought in the original product application.
Seeking approval for use in both adults and pediatric patients with the rare pediatric disease will not affect voucher eligibility.
Q6. What user fees apply to a rare pediatric disease product application?
A rare pediatric disease product application is subject to statutory requirements like any other application. Such applications may, however, be eligible for exemptions from some fees if they have received orphan-drug designation.
User fees also apply to applications for which a rare pediatric disease priority review voucher is used.
Q7. What are the sponsor's responsibilities after approval of a rare pediatric disease product application?
The sponsor of an approved rare pediatric disease product application must submit a report to FDA no later than 5 years after approval that addresses, for each of the first 4 post-approval years:
The estimated population in the U.S. with the rare pediatric disease for which the product was approved, both the entire population and the population aged 0 through 18 years
The estimated demand in the U.S. for the product
The actual amount of product distributed in the U.S.
Sponsors should submit such reports to the review division or office within CDER or CBER that reviewed the new drug application (NDA)/ biologics license application (BLA) for the rare pediatric disease product. This report should be prominently marked, “Rare Pediatric Disease Product Post-Approval Report.”
B. Requesting Rare Pediatric Disease Designation
Q8. What is the rare pediatric disease designation process?
Under the law as applicable at the time of issuance of this draft guidance, FDA may not award any vouchers after September 30, 2020, unless the application is for a drug that was designated as a drug for a rare pediatric disease by September 30, 2020.
If a sponsor chooses to request such designation, it shall do so “at the same time” that they submit a request for orphan-drug designation or a request for fast-track designation.
FDA will recognize a request for rare pediatric disease designation to be submitted “at the same time” as a request for orphan-drug designation or fast track designation if the requests are received by FDA within two weeks of each other.
While a request for rare pediatric disease designation may be submitted at the same time as a request for orphan-drug designation or fast track designation, each request should be submitted as a separate proposal.
The sponsor should indicate in the rare pediatric disease designation request whether or not it is requesting orphan-drug designation or fast track designation at the same time.
Timing of Requests for Orphan-Drug Designation:
Orphan-drug designation requests must be submitted before the sponsor’s filing of a marketing application for the drug for the orphan use.
Timing of Requests for Fast Track Designation:
Requests for fast-track designation may be submitted at the time of original submission of the investigational new drug (IND) application or any time thereafter prior to receiving marketing approval of the NDA or BLA, although FDA encourages that such requests be submitted no later than the sponsor’s preNDA/BLA meeting because many of the features of fast-track designation will no longer be applicable after that time.
Whether or not a sponsor receives rare pediatric disease designation for its drug, the sponsor must include a request for a rare pediatric disease priority review voucher in its original NDA/BLA submission (either in the initial package or up until the point of NDA/BLA filing) in order to be eligible to receive a voucher. See responses to Questions 14 and 15 for information on requesting such a voucher.
Q9. What information should these designation requests contain?
Sponsors should include the following information in rare pediatric disease designation requests:
(1) The name and address of the sponsor and the name of the sponsor’s primary contact person and/or resident agent including title, address, telephone number, and email address.
(2) The non-proprietary and trade name, if any, of the drug, or, if neither is available, person and/or resident agent including title, address, telephone number, and email address.
(3) The proposed dosage form and route of administration.
(4) A description of the rare pediatric disease for which the drug is being or will be investigated; the proposed use of the drug; and the IND number if previously assigned.
(5) A description of the drug to include (i) the identity of the active moiety, if it is a drug composed of small molecules, or of the principal molecular structural features, if it is composed of macromolecules, and (ii) its physical and chemical properties, if these characteristics can be determined.
(6) An explanation of the mechanism of action, with supportive data, suggesting that the drug may be effective in the rare pediatric disease.
(7) The basis for concluding that the drug is for a “rare disease or condition.”
(8) Documentation, with appended authoritative references, to demonstrate that the rare disease or condition for which the drug is proposed is a "rare pediatric disease".
Where a sponsor requests designation of a drug for only a subset of persons with a particular disease or condition that otherwise affects 200,000 or more people ("orphan subset" of non-rare disease or condition), a demonstration that, due to one or more properties of the drug, the remaining persons with such disease or condition would not be appropriate candidates for use of the drug including drug toxicity, mechanism of action, or previous clinical experience with the drug.
Q10. What is the process for submitting rare pediatric disease designation requests?
Sponsors should submit two copies, with at least one hard copy, of the completed, dated, and signed rare pediatric disease designation requests, with the information specified in Q9.
Q11. How will FDA respond to such designation requests?
The statute requires that FDA response will take one of the following forms:
A Deficiency Letter:
FDA will send a deficiency letter within the timeframe specified in Question 8 if the request lacks the information described in Question 9 or contains inaccurate or incomplete information. In the deficiency letter, the FDA will ask the sponsor to respond within 60 days or else request an extension of time to respond within that same timeframe; otherwise, FDA may consider the designation request voluntarily withdrawn.
Designating the Drug as a Drug for a “Rare Pediatric Disease” and Either Denying or Conditionally Designating the Application as a “Rare Pediatric Disease Product Application”:
FDA will designate a drug as a drug for a “rare pediatric disease” within the timeframe specified in response to Question 8 if the sponsor provides adequate information to demonstrate that the drug is for a rare pediatric disease and an adequate explanation, with supportive data, of the drug’s mechanism of action suggesting that the drug may be effective in the rare pediatric disease (see response to Question 9). FDA will evaluate prevalence as of the time of submission of the designation request. If FDA designates the drug as a drug for a “rare pediatric disease,” these prevalence estimates generally will not be reevaluated at the time of NDA/BLA submission, but FDA will evaluate the remaining eligibility criteria to determine whether the NDA/BLA is eligible for a priority review voucher (see Question 2).
Even if FDA designates the drug as a drug for a “rare pediatric disease,” FDA cannot definitively designate any associated marketing application as a “rare pediatric disease product application” because eligibility cannot be determined unless and until the application is approved or licensed. This is because eligibility depends on the contents of the application as well as certain facts at the time of approval or licensure (see Question 2). Short of designating the application, FDA has two options in responding to the application portion of a designation request:
(1) to conditionally designate the application as a “rare pediatric disease product application” assuming that, at the time of approval or licensure, it will meet all of the eligibility criteria. The final answer to a conditional designation of an application will come in the form of a voucher award or non-award at the time of marketing approval, if the sponsor requests such a voucher in the NDA/BLA.
(2) to deny designating the application if, at the time of submission of the designation request, it appears the application will fail to meet at least one of the criteria to be a rare pediatric disease product application. Even sponsors who have been denied such designation may request a voucher in their NDA/BLA submission if they believe they are eligible.
(3) Neither Designating the Drug as a Drug for a “Rare Pediatric Disease” Nor Designating the Application as a “Rare Pediatric Disease Product Application”: If FDA determines that the drug is not in fact a drug for a “rare pediatric disease,” FDA will deny rare pediatric disease designation of both the drug and the application. Reasons for such denial include:
the drug is not for a “rare disease or condition” under section 526 (e.g., prevalence in the U.S. is 200,000 or greater), and the drug is not for an “orphan subset” of a nonrare disease or condition
the drug is not for a disease or condition (or “orphan subset” of a disease or condition) that “is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years”
there is insufficient evidence to support the necessary prevalence estimates or to demonstrate an orphan subset
lack of an adequate explanation, with supportive data, of the drug’s mechanism of action suggesting that the drug may be effective in the rare pediatric disease
the request contains an untrue statement of material fact, omits material information, or is otherwise ineligible for designation
Voluntarily Withdrawn Letter: FDA may consider a designation request voluntarily withdrawn if the sponsor fails to respond to a deficiency letter, or to request an extension of time to respond, within 60 days of the deficiency letter date. In the event FDA considers a request voluntarily withdrawn, FDA will notify the sponsor in writing.
Not Accepted Letter: As noted in response to Question 8, FDA will not accept requests for rare pediatric disease designation received after FDA has already filed the NDA/BLA for the drug for the relevant indication. Such sponsors may still receive a voucher if they requested a voucher in the NDA/BLA submission and they are otherwise eligible.
Q12. What if a sponsor chooses not to submit a rare pediatric disease designation request before submitting the marketing application?
Sponsors who choose not to submit a rare pediatric disease designation request may nonetheless receive a priority review voucher if they request such a voucher in their original marketing application, meet all of the eligibility criteria. The determination of whether the drug is for a “rare pediatric disease” will occur as described above, except the prevalence determination will be based on the prevalence at the time of NDA/BLA submission rather than the prevalence at the time of designation request.
Sponsors who are interested in receiving a rare pediatric disease priority review voucher to notify FDA no later than a pre-NDA/BLA meeting.
C. Requesting a Rare Pediatric Disease Priority Review Voucher
Q13. Do sponsors need to receive rare pediatric disease designation before requesting a priority review voucher?
A sponsor does not need to receive rare pediatric disease designation for its drug in order to request a priority review voucher. However the FDA may not award a voucher (after September 30, 2020) unless the application is for a drug that was designated as a drug for a rare pediatric disease by September 30, 2020 and the application is approved by September 30, 2022.
Q14. When should sponsors request a rare pediatric disease priority review voucher?
Whether or not sponsors have requested rare pediatric disease designation, sponsors seeking a rare pediatric priority review voucher must submit a voucher request in the original submission of the potential rare pediatric disease product application – either in the initial package sent or up until the point of NDA/BLA filing. This voucher request should be prominently marked, “Rare Pediatric Disease Priority Review Voucher Request,” and be included or referenced in a cover letter.
Q15. What information should sponsors include in a priority review voucher request?
Depending on whether the sponsor has already received rare pediatric disease designation for the drug, the contents of the voucher request should include the following to support that the drug is for the prevention or treatment of a rare pediatric disease:
Sponsors Who Have Received Rare Pediatric Disease Designation for the Drug: Sponsors who have received rare pediatric disease designation for the drug should include that designation letter with the voucher request and need not re-analyze prevalence estimates at the time of NDA/BLA submission.
Sponsors Who Have Requested but Not Received Rare Pediatric Disease Designation for the Drug: Sponsors who have requested but not received rare pediatric disease designation should include in a voucher request the latest designation correspondence from FDA.
If the designation request has been denied or withdrawn, then the voucher request should include new prevalence estimates as of the time of NDA/BLA submission; otherwise, the sponsor can cross-reference the information in its designation request and provide additional information as necessary. In particular:
Sponsors who have received only an acknowledgment letter in response to a designation request should cross-reference their designation request (with associated prevalence estimates).
Sponsors who have received a deficiency letter should include a response to the deficiency letter with their voucher requests or else cross-reference a previously submitted deficiency response.
Sponsors who have received denial letters should explain how their drug is for a “rare pediatric disease” despite this denial, based on new information about the drug or the disease/condition, and include new prevalence estimates as of the time of NDA/BLA submission.
Sponsors Who Have Not Requested Rare Pediatric Disease Designation: Sponsors who have not requested rare pediatric disease designation should include in a voucher request prevalence estimates as of the time of NDA/BLA submission, with supporting documentation.
D. Using and Transferring a Rare Pediatric Disease Priority Review Voucher
Q16. What is a priority review?
The “priority review” awarded by the voucher is the same as the priority review referred to in the current PDUFA goals letter, which commits FDA to a goal of completing a certain percentage of priority reviews within the prescribed time frames.
Q17. What is a priority review voucher and when is it awarded?
A priority review voucher is a voucher that FDA issues to the sponsor of a rare pediatric disease product application at the time of the marketing application approval. This voucher entitles the holder to designate a single human drug application as qualifying for a priority review. Such a subsequent application would not have to meet the usual requirements for a priority review, but it would have to be submitted after the approval of the rare pediatric disease product application.
Q18. What form will the voucher take?
It will include information related to the priority review voucher in the approval letter for the rare pediatric disease product application and a priority review voucher identification number, which should be referenced when redeeming or transferring the voucher.
Q19. How and when can a voucher be used?
The application using the priority review voucher is not limited to drugs for rare pediatric diseases. The application using the voucher may be for a new indication of the same drug whose approval led to the award of the voucher. The sponsor redeeming the voucher must notify FDA of its intent to submit an application with a priority review voucher at least 90 days before submission of the application and must include the date the sponsor intends to submit the application.
This notification should be prominently marked, “Notification of Intent to Submit an Application with a Rare Pediatric Disease Priority Review Voucher.” Upon submitting this notification to FDA, the sponsor is obligated to pay the priority review user fee.
The voucher cannot be used if the application is submitted before the intended submission date.
The sponsor should submit a new notification informing FDA, at least 90 days before application submission, of its intent to submit a different human drug application with a priority review voucher and include the intended submission date.
Q20. Will these vouchers be transferable?
Yes. The sponsor of a rare pediatric disease drug receiving a priority review voucher may transfer (including by sale) the voucher to another sponsor. The voucher may be further transferred any number of times before the voucher is used, as long as the sponsor making the transfer has not yet submitted the application.
Q21. What is the procedure for voucher transfer?
Each person to whom a voucher is transferred must notify FDA of the change of voucher ownership within 30 days after the transfer. This notification should be prominently marked, “Transfer of Rare Pediatric Disease Priority Review Voucher” and submitted to the NDA/BLA.
It should include a letter from the previous owner to the current owner and a letter from the current owner to the previous owner, each acknowledging the transfer in addition to notifying FDA of the intent to submit an application with a priority review voucher. A complete record of transfer must be made available to FDA in order to redeem a transferred voucher.
Q22. What fees apply when using a priority review voucher?
The sponsor of a human drug application that is the subject of a priority review voucher must pay a priority review user fee in addition to any other required user fee. The amount of the priority review user fee will be determined each fiscal year and is based on the difference between the average costs incurred by FDA, in the previous fiscal year, of reviewing a priority review NDA/BLA and an NDA/BLA that is not subject to priority review.
Payment of this extra fee, to which the sponsor is legally committed as a result of the notification of its intent to use the voucher, is not subject to waivers, exemptions, reductions, or refunds.
FDA will establish the fee amount before the beginning of each fiscal year and will publish the fee schedule in the Federal Register.
Q23. When do I pay the priority review voucher user fee?
The priority review voucher user fee is due upon notifying FDA of the intent to submit an application with a priority review voucher. It is payable in accordance with procedures established by FDA, which will be described in the Federal Register notice that sets the fees for each fiscal year. The application will be considered incomplete if the priority review voucher user fee and all other applicable user fees are not paid in accordance with FDA payment procedures.
Q24. If I present a voucher to FDA for priority review, am I guaranteed a 6-month review on my drug application?
Although FDA’s goal is to take action on the application within 6 months after the 60-day filing period for an application involving a new molecular entity or within 6 months after the date of receipt of an application not involving a new molecular entity, this timeframe is not guaranteed. Note that “take action” in this context means that FDA aims to complete its review of the filed application and issue an approval or complete response letter within this timeframe; it does not mean that the application will be approved within this timeframe.
E. Specific Eligibility Questions
Q25. Is eligibility for a priority review voucher affected by whether the sponsor intends to market the rare pediatric disease drug after approval?
The FDA may revoke any priority review voucher if the rare pediatric disease drug for which the voucher was awarded is not marketed in the U.S. within 1 year following the date of approval.
Q26. Are drug-drug combinations eligible for priority review vouchers?
A drug-drug combination is eligible for a voucher if the product meets the criteria for a fixed-combination drug submitted. It will be eligible for a voucher if the product contains a drug substance, no active moiety of which has been approved in any other application.
Q27. Are drugs eligible for a priority review voucher if they have been approved and used in other countries but have not been previously approved by FDA?
Yes, as long as they meet all the criteria for a rare pediatric disease product application.
Q28. Is a drug that is already approved by FDA for another indication eligible for a priority review voucher for a rare pediatric disease product application?
No, for an application to qualify for a rare pediatric disease priority review voucher, it must be for a human drug that contains no active ingredient.
Q29. Would a new pediatric formulation for a drug already approved for adults be eligible for a rare pediatric disease priority review voucher?
No, an application for a drug containing a previously approved active ingredient (including any ester or salt of the active ingredient is not eligible to receive a rare pediatric disease priority review voucher.
Q30. Would an application for a rare pediatric disease drug submitted to FDA before enactment of PDUFA of 2012 (under FDASIA) but not yet approved qualify for a voucher?
No, the rare pediatric disease product sponsor may not receive a rare pediatric disease priority review voucher if the application was submitted to FDA prior to October 7, 2012 (90 days after the date of the enactment of PDUFA of 2012).
F. Relationship between Rare Pediatric Disease Designation and Orphan-Drug Designation
Q31. Will a drug that receives rare pediatric disease designation also qualify for orphandrug designation?
A “rare pediatric disease” also must be a “rare disease or condition” including those that affect fewer than 200,000 persons in the U.S. There are instances, however, where a drug may qualify as a drug for a “rare pediatric disease” but not qualify for orphan-drug designation, or vice versa. A drug might receive rare pediatric disease designation but not also immediately qualify for orphan drug designation.
Assume that a drug receives “rare pediatric disease” designation but is considered the “same drug” under the orphan drug regulations as an already approved drug for the same orphan use this drug would not be eligible to receive orphan drug designation absent a plausible hypothesis that it may be clinically superior to the already approved drug.
Assume a sponsor plans to develop a drug for a rare pediatric disease but so far has very little data suggesting that the drug may be effective in that disease this level of data may suffice for rare pediatric disease designation but generally it would not suffice for orphan-drug designation.
This is because, to qualify for orphan-drug designation, an applicant must supply sufficient information to establish a medically plausible basis for expecting the drug to be effective in the prevention, diagnosis, or treatment of the rare disease or condition.
The sponsor may eventually obtain orphan designation for the drug after developing or obtaining more supportive data for use of the drug for the rare disease or condition, including in vivo and/or clinical data in the rare disease or condition.
If a drug receives orphan-drug designation, it may be eligible for orphan-drug exclusivity, tax credits for qualified clinical testing, orphan product grant funding, as well as fee exemptions.
G. Agency’s Responsibilities and Roles
Q32. What are the Agency’s responsibilities if it issues a priority review voucher under section 529 or if it approves a drug application for which the sponsor used such a voucher?
FDA will publish a notice in the Federal Register and on its website within 30 days after issuing a priority review voucher within 30 days after approving a drug application for which the sponsor used such a voucher.
Q33. What are the different roles played by CDER, CBER, OOPD, and OPT?
CDER and CBER
The applicable review divisions and offices within CDER and CBER have the responsibility for premarket review of the rare pediatric disease product applications and for determining whether an application meets the eligibility criteria for receiving a priority review voucher. CDER and CBER will consult with OOPD and OPT as to whether a disease/condition is a “rare pediatric disease”.
OOPD and OPT
OOPD and OPT, both within the Office of the Commissioner, are distinct from CDER and CBER and are responsible for determining whether a drug (including a biological product) qualifies for designation as a drug for a “rare pediatric disease”.
Specifically, OOPD determines if the drug is for a rare disease or condition within the meaning of Section 526. OPT determines if the drug is for a disease that is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years. OOPD and OPT will consult with CDER and CBER as appropriate.
OOPD is also responsible for granting orphan-drug designation to drugs, including biological products. Whether a drug receives orphan-drug designation is a different question from whether it receives designation as a drug for a “rare pediatric disease”.
In the event a sponsor does not request rare pediatric disease designation but does request a rare pediatric disease priority review voucher at the time of NDA/BLA submission, the review division or office within CDER and CBER will consult with OOPD and OPT, as appropriate, as to whether the disease/condition is a “rare pediatric disease”.
Q34. Whom should I contact if I have questions about a rare pediatric disease product application?
Sponsors with questions not addressed in this guidance should contact OOPD for questions related to designation as a rare disease, OPT for questions related to designation as a rare pediatric disease, and the appropriate review division or office within CDER or CBER for questions related to rare pediatric disease product applications.