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Leveraging Orphan Drug Designation: A Regulatory Affairs Perspective

Updated: Jul 5, 2023

Welcome to our second blog post on RegAffairs Rx! In this edition, we delve into the fascinating world of orphan drug designation and its significance for rare disease indications. As regulatory affairs professionals, understanding the nuances and strategies behind orphan drug development is crucial in advancing treatments for patients with rare diseases.

Join us as we explore the regulatory landscape, benefits, challenges, and key considerations involved in leveraging orphan drug designation.


Orphan drug designation is a status granted by regulatory authorities such as the FDA and EMA to drugs intended to treat rare diseases or conditions. This designation provides several benefits to the drug developer, including tax credits for clinical trial costs, reduced fees, and a period of market exclusivity. In this blog post, we will explore the concept of orphan drug designation and its significance in the development of treatments for rare diseases.

Understanding Orphan Drug Designation:

Orphan drug designation is granted to drugs intended to treat rare diseases or conditions that affect fewer than 200,000 people in the United States (FDA) or that affect no more than 5 in 10,000 people in the European Union (EMA). The criteria for eligibility vary by regulatory authority but generally include a demonstration of the medical need for the drug and its potential to provide significant benefit to patients.

Rare diseases are often serious or life-threatening conditions with limited treatment options. Patients with these conditions have significant unmet medical needs and may face challenges accessing appropriate care. By incentivizing the development of treatments for rare diseases through orphan drug designation, regulatory authorities such as the FDA and EMA aim to improve the lives of these patients and advance our understanding of these complex conditions.

Advantages of Orphan Drug Designation:

More than half of all novel drugs approved by the FDA had orphan designations in 2020, 2021, and 2022. Of the orphan drugs available, 39% cost more than $100,000 annually. To reduce cost burden on the patient regulatory agencies give incentives to the pharmaceutical companies.

Orphan drug designation has become increasingly prevalent in the pharmaceutical landscape, with over half of all FDA-approved novel drugs in 2020, 2021, and 2022 having obtained this status. One of the key advantages of this designation is the period of market exclusivity. This means that once a drug is approved, no other company can market a similar drug for the same indication for a period of time (typically seven years in the United States and ten years in the European Union). This exclusivity provides a significant competitive advantage and can help ensure that the drug developer is able to recoup their investment.

Additionally, the high cost of orphan drugs, with 39% exceeding $100,000 annually, puts a burden on patients. To address this, regulatory agencies offer incentives to pharmaceutical companies In addition to market exclusivity, orphan drug designation also provides other benefits such as tax credits for clinical trial costs(25% tax credit on qualified trials) in the United States and reduced fees (partial or full waiver). These incentives can help reduce the financial burden of drug development and make it more feasible for companies to pursue treatments for rare diseases.

Expedited Regulatory Pathways:

Orphan drugs may also be eligible for expedited review and approval pathways such as accelerated approval and priority review this means that the FDA will review the drug application within six months, instead of the usual 10 months or accelerated assessment (EMA). These pathways can significantly reduce development timelines and help bring new treatments to patients in need more quickly. Orphan drugs are approved proportionally more often with one or more expedited programs than are nonorphan drugs.

For example, Zolgensma (onasemnogene abeparvovec-xioi), a gene therapy for spinal muscular atrophy (SMA) developed by AveXis (a subsidiary of Novartis), was granted priority review by the FDA in 2018. The FDA also granted Zolgensma Fast Track, Breakthrough Therapy and was approved in 2019 after demonstrating significant improvements in motor function in clinical trials. This expedited pathway allowed Zolgensma to reach patients in need more quickly than would have been possible through standard review processes.

Regulatory Strategies for Obtaining Orphan Drug Designation:

To apply for orphan drug designation, companies must submit an application to the relevant regulatory authority. This application must include information on the drug and its intended use, as well as evidence that the drug meets the criteria for orphan drug designation.

There are several strategies that companies can use to maximize their chances of a successful application. These include conducting thorough research on the disease or condition in question, engaging with patient advocacy groups and other stakeholders, and carefully preparing all necessary documentation.

Orphan Drug Designation: Beyond Regulatory Advantages:

In addition to the regulatory advantages discussed above, obtaining orphan drug designation can also provide other benefits such as increased funding opportunities and access to research grants. Companies with orphan drug designation may also be able to collaborate more closely with patient advocacy groups and other stakeholders to advance rare disease research and development.

Global Perspectives on Orphan Drug Designation:

Orphan drug designation programs exist in many countries around the world, including the United States (FDA), Europe (EMA), and Japan (PMDA). While these programs share many similarities, there are also some key differences in terms of eligibility criteria and benefits.

Companies developing drugs for rare diseases should carefully consider the international regulatory landscape when planning their development strategy. By understanding the requirements and benefits of different orphan drug designation programs, companies can maximize their chances of success.

Case Studies and Success Stories

There are many examples of pharmaceutical products that have successfully leveraged orphan drug designation to bring treatments for rare diseases to market. These treatments have had a significant impact on patients' lives and have helped advance our understanding of rare diseases.

One recent example is Palynziq (pegvaliase-pqpz), a treatment for phenylketonuria (PKU) developed by BioMarin Pharmaceutical. PKU is a rare genetic disorder that affects the body's ability to metabolize the amino acid phenylalanine, leading to a buildup of this substance in the blood and brain. Palynziq was granted orphan drug designation by both the FDA and EMA and was approved in 2018 after demonstrating significant reductions in blood phenylalanine levels in clinical trials.

Challenges and Limitations of Orphan Drug Designation

While orphan drug designation provides many benefits, there are also challenges and limitations associated with this status. One challenge is the high cost of developing drugs for rare diseases due to limited patient populations and complex regulatory requirements.

To overcome these challenges, companies may need to adopt innovative development strategies such as partnering with other companies or leveraging new technologies. By carefully considering these challenges and limitations, companies can maximize the value of orphan drug designation and bring new treatments to patients in need.

Other programs to consider while developing drugs for rare disease indications:

The Orphan Products Grants Program is a program of the Food and Drug Administration (FDA) that provides funding for clinical trials and natural history studies that advance rare disease medical product development. The program was created in 1983 to address the challenges of developing safe and effective medical products for rare diseases. Since its inception, the OOPD has funded over 80 clinical trials and natural history studies. These studies have helped to advance the development of safe and effective medical products for rare diseases.

The Rare Pediatric Disease Priority Review Voucher Program (PRV) was created by the FDA to incentivize the development of new treatments for rare pediatric diseases. A sponsor who receives approval for a drug or biologic for a rare pediatric disease may qualify for a voucher that can be redeemed for a priority review of a subsequent marketing application for a different product. This means that the sponsor can use the voucher to speed up the review of a new drug that is not for a rare disease or sold to another company. In 2017, bluebird bio sold a voucher for $102 million, showing their value in expediting the development and approval of new treatments.


In conclusion, orphan drug designation is a powerful tool for companies developing drugs for rare disease indications. By leveraging this status and taking advantage of the associated benefits, companies can increase their chances of successfully bringing new treatments to market. By understanding the complex landscape of orphan drug development, companies can navigate the regulatory process and bring innovative therapies to patients in need.

We hope this blog post has provided you with valuable insights into the regulatory affairs perspective of leveraging orphan drug designation. As you continue your journey in regulatory affairs, remember that your expertise and dedication contribute to improving the lives of patients and shaping the future of the pharmaceutical industry. Stay tuned for more informative content on RegAffairs Rx as we delve into various regulatory topics and empower regulatory professionals like you.

Together, let us continue to make a difference in advancing rare disease treatments and advocating for patients in need.

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