A Path Forward: The Journey to Orphan Drug Destination



The pharmaceutical industry is a complex landscape, and few areas are as crucial—and challenging—as the development and regulation of orphan drugs. These specialized medications hold the key to treating rare diseases that affect a small portion of the population—yet their impact is profound.

When it comes to regulatory affairs, understanding the journey to orphan drug destination is vital to both improving patient outcomes and advancing healthcare. In this blog, we’ll explore orphan diseases and drugs—understanding their significance, processes, challenges, and prospects.

Understanding Orphan Diseases

Rare diseases, often scientifically termed “orphan diseases” due to their limited occurrence, present unique challenges for patients and their families. Defined by a health condition affecting fewer than 200,000 individuals in the United States, rare diseases are twofold: emotionally isolating and financially difficult. As outlined by the Orphan Drug Act, there are over 10,000 recognized rare disorders, collectively impacting approximately 30 million Americans, which translates to about 1 in 10 people. The rarity of these diseases also poses significant hurdles to drug development, as traditional approaches may not be feasible. In turn, understanding the landscape of orphan diseases is crucial for comprehending the necessity and urgency of orphan drug development.

In 1983, the FDA established the Orphan Drug Act (ODA) to incentivize the development of promising drugs and biologics for the prevention, diagnosis, or treatment of rare diseases. Prior to the enactment of the ODA, development of drugs for rare diseases had been commercially risky, resulting in the approval of only approximately two drugs per year by the FDA. Since then, over a thousand drugs have been approved for rare diseases.

Orphan Drug Designation: Understanding the Application Process

The designation of a drug as an orphan drug is a pivotal moment in its journey towards regulatory approval. Understanding the criteria and benefits associated with orphan drug designation is essential for navigating the complex regulatory framework. There are several key aspects to consider when preparing your Orphan Drug Designation request.

Explanation of the Disease or Condition

Identifying the disease or condition is essential for estimating the patient population size, which is necessary to determine if the disease or condition qualifies as a rare or orphan disease. A common issue noted by FDA in reviewing Orphan Drug Designation requests is that a sponsor requests an Orphan Drug Designation for a specific indication. While marketing applications for a drug will be for a specific indication, Orphan Drug Designations are granted for a broader disease or condition. Additionally, when reviewing an Orphan Drug Designation, the FDA does not take into consideration the presence of an unmet need nor the sponsor’s desire to restrict the study of a drug to a specific population.

Scientific Rationale

The sponsor will need to provide sufficient scientific rationale to support the use of their drug in the selected disease or condition. In doing so, the sponsor must demonstrate promise for their drug to treat, diagnose, or prevent the selected disease or condition. This part of the application may include a description of the drug, its mechanism of action relevant to the disease or condition, and supporting in vivo, in vitro, or clinical study data for using the drug in patients with the selected disease or condition.

Population Estimate

The population estimate for the selected disease or condition is typically based on prevalence, which is the number of people in the US diagnosed with the disease or condition at the time the orphan drug designation application is submitted. In some cases, such as for acute diseases with a duration of less than a year, the FDA may allow sponsors to use an incident estimate, which is the annual number of new cases of the disease or condition. The sponsor is expected to provide sources and outline their methodology of estimating the population of a disease or condition in their application.

For diseases affecting more than 200,000 individuals, a sponsor may still be eligible for an Orphan Drug Designation if they can demonstrate that the drug targets an “orphan subset” of the non-rare disease or condition. To receive this designation, the sponsor must show that the drug is suitable for a specific subset of patients with the non-rare disease, but inappropriate for the rest due to certain characteristics or features of the drug, such as mechanism of action, toxicity profile, or prior clinical experience. The sponsor must clearly illustrate the drug's suitability for the subset while conveying its unsuitability for the broader patient population. Orphan subsets are rarely granted, and the rationale cannot be based solely on the sponsor's preference to study a specific subset.

Submitting your Orphan Drug Designation Request

As of November 2020, Orphan Drug Designations can be submitted electronically through the Orphan Drug Designation Portal, a part of the FDA NextGen Portal. This change is part of the FDA’s Orphan Drug Technology Modernization efforts and provides sponsors with enhanced, direct communication with the FDA regarding each submission. By providing these technological advances, the FDA is reaffirming its mission to advance the evaluation and development of safe and effective treatments for rare disease patients and families.

Obtaining orphan drug designation is just the beginning of the journey. Once designated, pharmaceutical companies must continue to meet rigorous regulatory standards to bring their drug to market. This includes conducting clinical trials, demonstrating safety and efficacy, and adhering to strict manufacturing practices. The FDA closely monitors the progress of orphan drug development, ensuring that these medications meet the highest standards of quality and safety.

Destination Orphan Drug: Why It Matters

The significance of achieving orphan drug status extends far beyond regulatory standardization—although that’s a crucial step of the puzzle. Accelerated drug development, market exclusivity, and increased investment opportunities are just some of the benefits that contribute to the commercial viability of orphan drugs. A sponsor who holds orphan drug designation may be eligible to receive tax credits for some of their clinical trial costs for qualified clinical testing and may be eligible for seven years of marketing exclusivity upon product approval. Perhaps most importantly, orphan drug status ensures improved access to treatment for patients facing rare diseases, offering hope where once solutions didn’t exist at all.

Challenges and Considerations

Despite the promise of orphan drugs, numerous challenges loom on the horizon. Regulatory hurdles, limited patient populations, and the delicate balance between commercial interests and patient needs are just a few of the obstacles that must be overcome. Addressing these challenges requires an integrated approach, one that prioritizes patient welfare while promoting innovation and investment in the correct ventures.


The journey to orphan drug destination may be challenging—but it’s one well worth undertaking. By advocating for the awareness of rare diseases and supporting the development of orphan drugs, we can make a difference in the lives of patients around the world.

Are you beginning the process in your orphan drug destination journey? Bracken is here to help.

Contact us today to learn about collaborating with Bracken’s regulatory team.

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