On July 31, 2024, the US Food and Drug Administration (FDA) announced Fiscal Year 2025 (FY2025) Prescription Drug User Fee Amendments of 2022 (PDUFA VII) fee rates for the review of human drug and biological product applications along with prescription drug program fees. As outlined in the table below, application fee rates, such as for a New Drug Application (NDA) or Biologics License Application (BLA), will increase by almost $300,000 in FY2025 (effective October 1, 2024).

 

Category	Fee Rates
	FY2025[i]	FY2024[ii]
Application requiring clinical data1	$4,310,002	$4,048,695
Application not requiring clinical data1	$2,155,001	$2,024,348
Program	$403,889	$416,734

¹ FDA defines “clinical data” as clinical data (other than bioavailability [BA] or bioequivalence [BE] studies) with respect to safety or effectiveness that are required for approval.

The FDA has provided guidance[iii] on various ways to obtain a waiver or reduction of the application fees in accordance with section 736(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) such as:

• Waiver or reduction is necessary to protect the public health
  • For example, is the product recognized as an effective treatment option that significantly impacts the public health and does the company developing the drug have limited resources to fully develop the drug?
• The assessment of the fee would present a significant barrier to innovation because of limited resources available to the person or other circumstances
  • For example, has the drug product been designated as a priority drug, accepted into one of FDA’s expedited programs for serious conditions, or granted fast track or breakthrough status and does the company developing the drug have limited resources to fully develop the drug?
• The applicant is a small business (having fewer than 500 employees, including affiliates) submitting its first human drug application to FDA for review
• The product has been designated an Orphan Drug and is therefore exempt from the application fee 

Fee Reduction Strategies for Repurposed Drugs

Under Section 505(b)(2) of the FD&C Act, a Sponsor of a new small molecule drug product leverages information from other drug approval packages and/or published information they do not own or have right of reference to. Typically, new drug development under the 505(b)(2) pathway requires less capital and time and has a higher success rate versus the 505(b)(1) pathway, where the Sponsor develops safety and effectiveness information from scratch.

From a clinical perspective, 505(b)(2) programs are unique since the number and type of clinical studies the Sponsor needs to conduct for approval varies widely. Some programs receive approval without any Sponsor-conducted clinical studies (e.g., based entirely on published literature), others entail one or more bioavailability/bioequivalence (BA/BE) studies, and on the far end of the spectrum, larger clinical efficacy and safety programs may be needed, such as when the Sponsor is developing the drug for a new indication. In the former two scenarios, since only literature or BA/BE studies are needed for approval, these types of programs typically qualify for the reduced application fee; however, it is important to confirm this early with the Agency, such as during a pre-Investigational New Drug application (pre-IND) meeting. For the latter situation, unless a specific waiver or reduction applies, the full application fee is required since the Sponsor needs to conduct clinical efficacy and safety studies.

Since the application fee reduction is significant, it is important to consider a 505(b)(2) development strategy that qualifies for a reduced application fee, whenever possible. The following are several situations where the correct strategy can avoid the full application fee.

Model Informed Drug Development (MIDD)

MIDD techniques, which are increasingly being embraced by FDA as part of Model-Informed Product Development (MIPD)[iv], can be used to avoid clinical efficacy and safety studies in special patient populations. For example, pharmacokinetic (PK) data from a comparative BA study and PK modeling approaches (e.g., Mechanism-Based PK/PD Modeling, Population PK/PD Modeling, Physiologically-Based Pharmacokinetic [PBPK] Modeling, Concentration-QT analysis) can be used to assess impacts on efficacy and safety and justify unique safety issues in special populations (e.g., patients with renal, hepatic, or cardiovascular concerns). Since dedicated efficacy and safety trials are avoided and only a comparative BA study is required for approval, the 505(b)(2) NDA would qualify for the reduced PDUFA application fee, saving ~$2.1M.

Literature

Literature is often leveraged in a 505(b)(2) application to support the safety of the new drug, even for programs that rely on a Listed Drug (LD). For example, a scientific bridge between the Sponsor’s product and the LD may be established in a comparative BA study and allow bridging to both the safety and efficacy data from the LD. However, if the scientific bridge cannot be established because systemic exposures fall above or below those of the LD, additional safety or efficacy data, respectively, may be needed and this can sometimes be justified based on a compilation of the clinical literature for the drug. As with the previous example, since only a comparative BA study is required for approval, it would qualify for the reduced application fee.

Orphan Drug Designation

As mentioned, if a Sponsor’s product has Orphan Drug Designation (ODD), no application fee is required, and this also applies to 505(b)(2) programs. Navigating the ODD requirements and justifying why a Sponsor’s product qualifies for ODD can be tricky, especially for a condition that might be viewed as an “orphan subset” where a scientific explanation of why the use of the drug outside of that subset population would be inappropriate due to some properties of the drug. For example, drug toxicity, mechanism of action, or previous clinical experience with the drug. Providing a robust scientific justification to obtain ODD can pay dividends in not only avoiding the PDUFA application fee but also obtaining 7-year Orphan Drug Exclusivity (ODE) and receiving tax credits for qualified clinical studies.

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Leverage our extensive knowledge in developing strategies to reduce PDUFA fees for both novel and repurposed drugs, and at the same time streamlining and accelerating your drug development program, contact us. It can simply start with a strategic assessment of your drug product.

[i] United States Federal Register. Prescription Drug User Fee Rates for Fiscal Year 2025. 89 FR 61474. Docket No. FDA-2024-N-0007. July 31, 2024.

[ii] United States Federal Register. Prescription Drug User Fee Rates for Fiscal Year 2024. 88 FR 48881. Docket No. FDA-2023-N-2850. July 28, 2023.

[iii] US Food and Drug Administration. Prescription Drug User Fee Act Waivers, Reductions, and Refunds for Drug and Biological Products. Guidance for Industry. October 2019.

[iv] US Food and Drug Administration. Focus Area: Model-Informed Product Development. Website: https://www.fda.gov/science-research/focus-areas-regulatory-science-report/focus-area-model-informed-product-development. Accessed August 4, 2024.