BPG Blog rare pediatric disease update

BPG Blog: Rare Pediatric Disease Designation Priority Review Voucher Update

Rare Pediatric Disease Designation Sunset Clause

In June of 2020, BioPharma Global wrote a blogpost describing the rare pediatric disease designation (RPD) and voucher programs, noting they will sunset on September 30th, 2020. This required all companies applying for a rare pediatric disease priority review voucher (PRV) after this date to have already been granted RPD for a specific product while requesting a rare pediatric disease PRV by September 30th, 2022, at which point the program would end (Click here to read our RPD Sunset Clause Blogpost)1.

Since our original blogpost, congress has passed legislation to extend the RPD and voucher program to sunset on September 30th, 2024. After September 30th, 2024 FDA will no longer grant PRV to those without RPD, and after September 30th, 2026, FDA will stop granting rare pediatric disease PRV (unless this program is further extended).2 BioPharma Global continues to offer strategy assessments and data reviews related to RPDs, submissions of RPD applications, and writing of RPD applications in addition to our other services (BioPharma Global Services).

The Rare Pediatric Disease Designation and Voucher Program

What is a rare pediatric disease?

Rare pediatric diseases are most currently defined by the 2016 Advancing Hope Act:

 

(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, within the meaning of section 526 [of the FD&C Act]3-5.

What is the rare pediatric disease designation and voucher program?

The Rare Pediatric Disease Designation (RPD) and Voucher program was established in the federal Food, Drug, and Cosmetic Act in 2012 and is outlined in section 5295. This program was developed to promote the discovery and invention of drugs that treat or prevent rare pediatric diseases by granting priority review vouchers (PRV) to companies whose products concern rare pediatric patient populations3. Rare pediatric disease PRVs grant the redeemer (for a redemption fee) an expedited new drug application (NDA) or biological license application (BLA) review by the FDA in approximately 6 months compared to the standard 10 month time frame6.

What is the process of applying for RPD and subsequent voucher?

The FDA recommends companies looking to request a rare pediatric disease PRV first apply for a RPD for a particular product3. The RPD application may be applied for separately prior to submitting a rare pediatric disease marketing application and a rare pediatric disease PRV request. If a company receives a RPD prior to marketing application, then at the time of marketing application the company will only need to submit their designation letter and the request for the rare pediatric disease PRV along with the marketing application. For companies wishing to have a RPD review within 60 days of submission, the RPD application must be accompanied with an orphan drug designation application or fast track designation application (within two weeks of submission of one another)3. RPD applications may be submitted alone, but there is no time guarantee for review of RPD submissions without orphan drug designation or fast track designation applications. The requirements outlined by the FDA for a drug company to receive approval for a rare pediatric disease product application and subsequent PRV are:

(A) […] a human drug application as defined in section 735(1) of the FD&C Act:

For prevention or treatment of a rare pediatric disease

That contains no active ingredient (including any ester or salt of the active ingredient) that has been previously approved in any other application under section 505(b)(1), 505(b)(2), or 505(j) of the FD&C Act or section 351(a) or 351(k) of the PHS Act.

(B)That FDA deems eligible for priority review.

(C) Is submitted under section 505(b)(1) of the FD&C Act or section 351(a) of the Public 181 Health Service Act.

(D) Relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population (see Question 4*).

(E) Does not seek approval for an adult indication in the original rare pediatric disease product application (see Question 5*); and

(F) Is approved after the date of enactment of the Advancing Hope Act of 2016 (September 30, 2016)3,5.

*Answers to questions 4 and 5 may be found in the FDA’s draft guidance on Priority Review Vouchers3

These requirements must be met by the time a company applies for marketing approval (through an NDA or BLA) because the rare pediatric disease PRV request is submitted at the same time as an NDA or BLA for a particular product (during initial submission of these documents)3. Currently, rare pediatric disease PRVs can be requested when applying for marketing approval without having previously received a RPD. As stated above, the program has been extended to sunset on September 30th, 2024, and after this date, companies wishing to receive a rare pediatric disease PRV for products will only be eligible to receive a PRV if they have been granted a RPD by this date2.

If a company’s rare pediatric disease drug product has been approved for market, the company will receive a rare pediatric disease PRV along with their approval notification3. PRVs do not need to be redeemed by the company who initially received them and can be transferred for profit an unlimited number of times3. Companies have previously sold their rare pediatric disease PRV for a large profit, for example, between 80 to 110 million US dollars6.

The RPD and priority review program will begin sunsetting in September, 2024. As mentioned, after September 30th, 2024, rare pediatric disease PRVs will only be granted by the FDA if a company has been awarded a RPD for a drug product by September 30th, 2024, and after September 30th, 2026, rare pediatric disease PRVs will no longer be awarded (unless legislation is again passed that extends this program)2.

For more information such as specifics to be included in rare pediatric disease designation request or individual offices to contact please visit the following websites:

References:

      1. FDA. Rare Pediatric Disease (RPD) Designation and Voucher Programs. https://www.fda.gov/industry/developing-products-rare-diseases-conditions/rare-pediatric-disease-rpd-designation-and-voucher-programs. Published 2017. Accessed 6/11/2020.
      2. FDA. Rare Pediatric Disease (RPD) Designation and Voucher Programs. 2021.
      3. FDA. Rare Pediatric Disease Priority Review Vouchers Guidance for Industry: Draft Guidance. 2019.
      4. FDA. Orphan Drug Act. 1983.
      5. FDA. Federal Food, Drug, and Cosmetic Act. 2012.
      6. Mezher M, Gaffney A, RAC., Brennan Z. Regulatory Explainer: Everything You Need to Know About FDA’s Priority Review Vouchers. https://www.raps.org/regulatory-focus/news-articles/2017/12/regulatory-explainer-everything-you-need-to-know-about-fdas-priority-review-vouchers. Published 2020. Accessed.

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

RPD-Sunset

BPG Blog: Rare Pediatric Disease Designation Sunset Clause

Rare Pediatric Disease Designation Sunset Clause

The Rare Pediatric Disease designation (RPD) and voucher program was established in the federal Food, Drug, and Cosmetic Act in 2012 and outlined in section 5291. This program was developed to promote the discovery and invention of drugs that treat or prevent rare pediatric diseases by granting priority review vouchers (PRV) to companies whose products concern rare pediatric patient populations2. Rare pediatric PRVs grant the redeemer (for a redemption fee) an expedited new drug application (NDA) or biological license application (BLA) review by the FDA in approximately 6 months compared to the standard 10 month time frame3. Based on the current language of the legislation, this program set to begin phasing out on September 30th, 2020, requiring all companies applying for a rare pediatric PRV after this date to have an RPD for a specific product, and will come to a complete halt by September 30th, 2022. This post serves to highlight the important upcoming changes as this program approaches it’s deadline4.

 Rare pediatric diseases are most currently defined by the 2016 Advancing Hope Act:

(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, within the meaning of section 526 [of the FD&C Act]2,5.

The FDA recommends companies looking to request a rare pediatric disease PRV first apply for an RPD for a particular product2. The RPD application has less requirements than the rare pediatric disease marketing application accompanying a PRV request, and is applied for separately prior to submitting a rare pediatric disease marketing application and a rare pediatric PRV request2. The requirements outlined by the FDA for a drug company to receive approval for a rare pediatric disease product application and subsequent PRV are:

(A) […] a human drug application as defined in section 735(1) of the FD&C Act:

– For prevention or treatment of a rare pediatric disease

– That contains no active ingredient (including any ester or salt of the active ingredient) that has been previously approved in any other application under section 505(b)(1),  505(b)(2), or 505(j) of the FD&C Act or section 351(a) or 351(k) of the PHS Act1.

(B)That FDA deems eligible for priority review.

(C) Is submitted under section 505(b)(1) of the FD&C Act or section 351(a) of the Public 181 Health Service Act.

(D) Relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population (see Question 4*).

(E) Does not seek approval for an adult indication in the original rare pediatric disease product application (see Question 5*); and

(F) Is approved after the date of enactment of the Advancing Hope Act of 2016 (September 30, 2016)1,2.

*Answers to questions 4 and 5 may be found in the FDA’s draft guidance on Priority Review Vouchers2

These requirements must be met by the time a company applies for marketing approval (through an NDA or BLA) because the rare pediatric disease PRV request is submitted at the same time as an NDA or BLA for a particular product (during initial submission of these documents)2. Currently, rare pediatric PRVs can be requested when applying for marketing approval without having previously received a RPD. However as stated above, there is an upcoming clause which explains that after September 30th, 2020, companies wishing to receive a rare pediatric PRV for products will only be eligible to receive a PRV if they have been granted an RPD by this date.

If a company’s rare pediatric disease drug product has been approved for market, the company will receive a rare pediatric disease PRV along with their approval notification2. PRVs do not need to be redeemed by the company who initially received them, and can be transferred for profit an unlimited number of times2. Companies have previously sold their rare pediatric PRV for a large profit, for example, between 80 to 110 million US dollars3.

The RPD and priority review program will end in September 20224. As mentioned, after September 30th, 2020, rare pediatric PRVs will only be granted by the FDA if a company has been awarded a RPD for a drug product by September 30th, 2020, and after September 30th, 2022, rare pediatric PRVs will no longer be awarded4. Companies still wishing to gain RPD prior to September 30th, 2020, must apply for this designation by July 31st, 2020, and this application must be accompanied (within two weeks of submission of one another) by an Orphan Drug designation application or Fast Track application, which grants the RPD a guaranteed review time of 60 days4. The July 31st deadline gives FDA enough time to review the application and make an informed decision by September 30th, 2020. Any RPD submissions after July 31st, 2020 would not be able to be processed by September 30th and therefore will not be accepted4.

Following September 30th, 2020 there will be no need for RPD applications, and the entire initiative will be complete on September 30th, 2022, unless current legislation is updated to extend the rare pediatric PRV program. For more information or individual offices to contact please visit any of the following websites:

References:

    1. FDA. Federal Food, Drug, and Cosmetic Act. 2012.
    2. FDA. Rare Pediatric Disease Priority Review Vouchers Guidance for Industry: Draft Guidance. 2019.
    3. Mezher M, Gaffney A, RAC., Brennan Z. Regulatory Explainer: Everything You Need to Know About FDA’s Priority Review Vouchers. https://www.raps.org/regulatory-focus/news-articles/2017/12/regulatory-explainer-everything-you-need-to-know-about-fdas-priority-review-vouchers. Published 2020. Accessed.
    4. FDA. Rare Pediatric Disease (RPD) Designation and Voucher Programs. https://www.fda.gov/industry/developing-products-rare-diseases-conditions/rare-pediatric-disease-rpd-designation-and-voucher-programs. Published 2017. Accessed 6/11/2020.
    5. FDA. Orphan Drug Act. 1983.

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

04232020

BPG Blog: FDA COVID-19 Regulatory Strategies

FDA Regulatory Strategies for Potential COVID-19 Treatments, Diagnostics, and Vaccines

As the world is in the midst of the novel coronavirus (COVID-19) pandemic, the Food and Drug Administration has been working to provide insight into regulatory pathways for companies with potential treatments, diagnostics, or vaccines for COVID-19. These regulatory pathways are aimed at initiating rapid interactions with the FDA to expedite the development of tools addressing the COVID-19 pandemic. The following compiled information describes these regulatory pathways.

Note: Information on this page will update as needed when new FDA regulatory pathways for COVID-19 are discovered.

Guidances to Support the Accelerated Development of Novel Prevention and Treatment Options for COVID-19

  • COVID-19 Public Health Emergency: General Considerations for Pre-IND (Investigational New Drug application) Meeting Requests for COVID-19 Related Drugs and Biological Products.
    • This guidance outlines a more efficient process for developers to receive agency feedback on their supporting data with the goal of starting clinical trials as soon as possible. The FDA is committed to helping sponsors get potentially effective products into study quickly, while protecting the safety of patients. To that end, the guidance provides sponsors clarity on the types of data and information they should provide to address clinical, nonclinical and quality considerations before submitting an application to initiate studies.
  • COVID-19: Developing Drugs and Biologics for Treatment or Prevention.
    • This guidance provides FDA current recommendations on later stage clinical trials intended to establish safety and effectivness for COVID-19 products. The guidance outlines critical sponsor considerations such as appropriate patient selection, including the evaluation of therapies in patients at high risk of complications from COVID-19 (e.g., the elderly). In addition, the guidance helps sponsors to understand how to design their trials, including considerations of study duration, assessment of efficacy and monitoring for safety. The FDA anticipates this guidance will help sponsors to efficiently design studies that may lead to the review and potential approval of safe and effective drugs and biological products to address the COVID-19 pandemic.

For Drug Developers

Coronavirus Treatment Acceleration Program (CTAP)

CTAP is a newly established special emergency program for potential COVID-19 therapies. This program is intended for rapid review of products in the Pre-IND or IND phases of drug development. Sponsors should send requests to the FDA with any questions or available information regarding their potential treatment. Requests should include detail about the treatment, safety data, and any data demonstrating efficacy against COVID-19, including the SARS-CoV-2 virus which causes the COVID-19 disease. Sponsors developing potential therapeutics are recommended to submit requests to [email protected] (See FDA Coronavirus Treatment Acceleration Program (CTAP) for more details).

Upon receipt, requests will be reviewed by FDA staff and sponsors should receive a response within 24 hours. Additionally, single patient expanded access requests will be responded to within 3 hours of receipt. Products with the most detail, scientific rationale, and those at the most advanced stages of development will be prioritized.

Pre-IND Consultation Program (for General Correspondence and Formal Meetings)

Sponsors with investigational products with preclinical data showing efficacy against COVID-19 or SARS-CoV-2 virus (including cell culture and/or animal model data) can submit to the FDA a Pre-Investigational New Drug (Pre-IND) request via the form FDA 1571. This request can be made for  “general correspondence” and include any available information regarding the therapy (See COVID-19 Therapeutics: General Information for Interested Stakeholders for more details).

When ready, Sponsors may submit a request via the form FDA 1571 for a formal Pre-IND meeting (See Division of Antivirals Pre-IND letter of instruction and Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products for more details).

  • Sponsors can request face-to-face, teleconference, video conference, or written responses
  • Meeting requests are to be submitted electronically (see Electronic Common Technical Document (eCTD)) or by paper to CDER
  • Include as much information about treatment as possible including information on CMC, Pharmacology/Toxicology, microbiology/virology, proposed and completed animal studies, and clinical development plan
  • FDA will notify the Sponsor within 21 days of receipt of meeting request with information on the date by which it intends to respond to the Sponsor’s questions

For additional information on the Pre-IND Consultation program, Sponsors may call 301-796-1500.

For Therapies Without Activity Information

Sponsors developing potential treatments against COVID-19 but who lack sufficient activity information may consult with the National Institutes of Health, Division of Microbiology and Infectious diseases website for information about preliminary screening activities available for Sponsors of potential antiviral products.

For Diagnostic Test Developers

Emergency Use Authorization (EUA)

Sponsors seeking to develop and perform diagnostic tests to detect SARS-CoV-2  with potential COVID-19 diagnostics are recommended to submit a request for EUA using an EUA template to the FDA. Such Sponsors may include:

  • Laboratories certified under Clinical Laboratory Improvement Amendments (CLIA)
  • State-authorized laboratories certified under CLIA that meet CLIA regulatory requirements to perform high-complexity testing
  • Commercial manufacturers developing serological tests to identify SARS-CoV-2 from clinical specimens, such as in laboratories or by healthcare workers at the point-of-care (does not include at-home testing)  

Prior to use, FDA requires all clinical tests to be validated. The validation tests which Sponsors should consider will vary based on the type of diagnostic test and include limit of detection, cross-reactivity, and microbial interference tests among others (see Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff).

The FDA expects Sponsors to prepare and submit an EUA request within 15 business days for a test with validated performance. FDA believes 15 business days is a reasonable time in which to prepare EUA submission for appropriately validated tests.

Sponsors can submit requests using provided EUA templates:

Pre-EUA

Before submitting their EUA request, Sponsors may reach out to the Division of Microbiology Devices at (301) 348-1778 or [email protected] for feedback before test validation and documentation is completed.

For more information on pathways for diagnostics for COVID-19, please see the FDA guidance  FAQs on Diagnostic Testing for SARS-CoV-2, the FDA guidance “Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff, and the FDA letter “Laboratories Who Have Developed a Molecular-Based Test (LDTs) for Coronavirus Disease 2019 (COVID-19).”

For Vaccine and Biologic Developers

Currently, there is limited information on regulatory pathways for Sponsors developing vaccines and biologics for COVID-19. At present, FDA encourages biological product Sponsors and vaccine developers to contact the CBER Manufacturers Assistance and Technical Training Branch (MATTB) via email at [email protected] or via phone at 1-800-835-4709. CBER should reply to any email inquiries within 5 business days.

On weekends, holidays, and after 4:30 pm on weekdays requests for expanded access for emergency use for biologics should be directed to the FDA Emergency Call Center at 1-866-300-4374 or 301-796-8240.

Other Pathways for Treatments, Diagnostics, and Vaccines

CoronaWatch Meeting Request (Medical Countermeasures)

The Biomedical Advanced Research and Development Authority (BARDA) has launched a website requesting information from Sponsors of products and technologies including diagnostics, therapeutics, and vaccines, relevant to addressing the COVID-19 pandemic. These products must have gone through preclinical trials, have established a large-scale cGMP manufacturing capability, and/or have utilized an approved platform. Sponsors interested in submitting information and requesting a meeting should include a brief description of their product accompanied by a slide deck, manuscript, publications, and any other non-confidential information for review. Through this pathway, submission of information does not guarantee a meeting or any funding of the product. 

See Request a USG CoronaWatch Meeting or contact [email protected] for more information.

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.