Blog Writer

Rare Disease Drug Development Challenges:
A Strategic Guide.

Sam Tomlinson
Sam Tomlinson
VP of Global Drug Safety

Sam has over 20 years strategic and operational experience in global Pharmacovigilance in both large pharma and small to medium sized pharma organizations.

Sam also has experience as an EU QPPV and her expertise spans across the product lifecycle from clinical trials, through post marketing and product discontinuation.

Additionally, she has managed and supported numerous Health Authority inspections including EMA, FDA, MHRA, ANSM, Health Canada, HPRA, and AIFA.


The pharmaceutical landscape is rife with challenges, and the development of new medicines is no exception. The already slim odds of success, ranging from 30 to 60%, become even more daunting when it comes to orphan indications and rare diseases. In this short article, we delve into the distinctive hurdles faced by pharmaceutical companies in this specialized field and explore strategic approaches to bolster the chances of success.

What are the Key Considerations in Developing Medicines for Rare Diseases?

Small Patient Populations and Data Challenges.

Rare diseases are characterized by small patient populations, posing a significant challenge in gathering robust data for regulatory approval. According to a study published in the Orphanet Journal of Rare Diseases1, approximately 72% of rare diseases affect fewer than 1 in 5,000 individuals. This scarcity of patients makes it imperative for pharmaceutical companies to meticulously plan and also consider more novel options for their data collection strategies.

Early Engagement with Regulatory Agencies is Critical.

In a survey conducted by the Tufts Center for the Study of Drug Development2, it was found that companies that interacted with regulatory agencies early in development were more likely to receive expedited reviews and approvals. Well planned and evidence based strategic discussions in the early clinical phases can help align expectations and improve the likelihood of a successful Marketing Authorization Holder (MAH) application.

Advance Strategic Planning for Risk Management and Pharmacovigilance Activities.

For medicines with identifiable risks or complex formulations, the Pharmacovigilance (PV) infrastructure can become a substantial financial burden. According to a report by the U.S. Food and Drug Administration (FDA)3, the implementation of Risk The implementation of Risk Evaluation and Mitigation Strategies (REMs) can incur costs ranging from hundreds of thousands to millions of dollars and in Europe the implementation of additional Risk Management Measures (aRMM) can also be highly costly.

However, a well-crafted risk management plan with a well-defined benefit / risk profile will minimise the possibility of over conservative conditions being imposed upon approval.   As described in a review in Therapeutic Innovation & Regulatory Science, a targeted approach during the development phase facilitates the implementation of cost-effective risk management measures. This not only ensures compliance with regulatory expectations but also contributes to a safer and more efficient development process.

Risk Evaluation and Mitigation Strategies (REMs) and Additional Risk Management Measures (aRMM):

In the context of developing medicines for rare diseases, the ensuring appropriate methodologies for managing risk are crucial but can critically influence a medicines financial viability.

  • REMs are comprehensive strategies employed by pharmaceutical companies to manage known or potential risks associated with a drug. These strategies go beyond routine pharmacovigilance and may include educational programs for healthcare professionals, patient registries, and restricted distribution programs.
  • aRMM, on the other hand, encompasses additional risk management measures that go beyond standard pharmacovigilance activities. These may include specific monitoring protocols, enhanced communication strategies, or specialized training for healthcare providers. The goal is to ensure that the benefits of the medication outweigh the risks, especially in the context of rare diseases where patient populations are limited.

The Cost Implications:

Implementing Risk Evaluation Mitigations Strategies (REMS) and additional Risk Minimisation Measures aRMM can be financially burdensome, as highlighted by the U.S. FDA report mentioned earlier. Whilst, this investment may be essential for ensuring the safety and efficacy of the drug, particularly in situations where traditional risk management approaches may not be sufficient.

However, companies must carefully assess the safety profile of their products to be sure that any measures implemented are proportionate to and appropriate for the identified risks. This will enable them to anticipate and weigh the costs of implementing these measures against to ensure the financial viability of the product, considering the unique challenges associated with rare diseases. Taking time to make these assessments will increase the likelihood that companies will be able to bring the product to market dramatically improving the lives of patients.

Local and Regional Qualified Person Responsible for Pharmacovigilance (QPPV) Requirements:

The costs of REMS and aRMM are not the only potential significant costs to be considered in bringing medicines to market. In Europe, some of the strategies designed to support approval of medicines for rare diseases will require medicines to be centrally authorised. In theory this will require both national and regional pharmacovigilance requirements to be met prior to launch. Therefore, having a well-defined strategy for the provision of local and regional QPPVs is paramount.

The QPPV is responsible for overseeing the safety of medicinal products and plays a crucial role in risk management in the country or region for which they are assigned.

Having a strong understanding of the local requirements will ensure that costs relating to the provision of local personnel can be managed whilst continuing to ensure compliance with regulation.

Strategic Planning for Local and Regional QPPV:

Strategically planning for local and regional QPPV involves early identification of when and where the drug is intended to be marketed.

Understanding the diverse regulatory requirements in these regions allows for the appointment of QPPVs with the necessary expertise and knowledge of local pharmacovigilance expectations at the appropriate time between MAH application and launch.

This strategic approach ensures that the pharmacovigilance activities align with local and regional regulations, optimizing the overall Pharmacovigilance System at the same time as managing cost.


The journey of developing medicines for orphan indications and rare diseases is undoubtedly challenging, but with strategic planning, early engagement with regulatory agencies, and a targeted approach to risk management, pharmaceutical companies can enhance the likelihood of success. By incorporating facts and figures into their strategies, stakeholders can not only navigate these challenges effectively but also contribute to advancing medical innovation and improving the lives of patients with rare diseases.

1 Orphanet Journal of Rare Diseases. Epidemiology of Rare Diseases 20 January 2020
2 DiMasi, J. A., & Getz, K. A. (2019). Early interactions between drug sponsors and regulatory agencies: effects on timing and outcomes of new drug development. Therapeutic innovation & regulatory science, 53(3), 362-369
FDA. (2018). Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry