The Urgency for Rare Disease Regulatory Harmonization

are diseases affect close to 440 million people globally, yet around 95% lack approved therapies. Families face diagnostic odysseys lasting years, often enduring worsening symptoms while waiting for diagnosis or treatment. In India, over 70 million people may be affected, but most remain unrecognized in formal registries and policy priorities.

The World Health Assembly’s May 2025 resolution designated rare diseases as a global health priority, mandating the WHO to coordinate a 10-year plan for better diagnosis, registries, and access. Yet the gap between aspiration and on-the-ground reality remains wide.

In affected Indian households, rare diseases are not only medical emergencies but financial catastrophes. Treatments, when available, can cost upwards of ₹1 crore (over 110,000 USD) per year, far beyond their reach. Families rely on crowdfunding or on government-provided financial support of ₹50 lakh (USD 57,000) per patient. The system fails not because India lacks ingenuity or talent, but because of structural policy, regulatory, and reimbursement inefficiencies.

The key question arises: Can India adopt global best practices—like exclusivity incentives, tax credits, and registry-driven policymaking—while designing solutions tailored to its vast population and constrained resources?

Facts and Takeaways

Global Frameworks: US and EU
Policy innovations in the United States and European Union show what is possible.

• The US FDA Orphan Drug Act (1983) grants seven years of market exclusivity, tax credits for R&D, fee waivers, and pathways like Fast Track and Accelerated Approval.
• The EU EMA Orphan Regulation (2000) provides 10 years of exclusivity (12 years for pediatric therapies), major fee reductions, and centralized approval through the EMA. Applicants and their products benefit from advice by the Committee for Orphan Medicinal Products (COMP).

These frameworks fostered a thriving ecosystem: almost 7,500 orphan designations and 1,352 FDA approvals to date. Importantly, both regions link policy to coordinated public funding and research networks such as NIH NCATS, the Rare Diseases Clinical Research Network, and the EU’s ERDERA and European Reference Networks.

The reliance on patient registries, natural history studies, and innovative trial designs (basket, platform, Bayesian adaptive) has accelerated research. Both FDA and EMA now accept digital health technologies (DHTs), wearables, and in silico trial models as part of regulatory decision-making [FDA MIDD; EMA AI].

India’s Progress and Persistent Gaps
India’s rare disease ecosystem is nascent but growing.

• Policy base: The National Policy for Rare Diseases (2021) and the New Drugs and Clinical Trials Rules (2019) offer some reforms, including the establishment of a National Consortium for Research and Development on Therapeutics for Rare Diseases (NCRDTRD) to promote domestic orphan drug R&D; Promotion of Research and Innovation in Pharma MedTech sector (PRIP) to accelerate domestic therapeutic discovery, development, and commercialization; and Clinical Trial Waiver for orphan therapies approved by the FDA, EMA, and other specified agencies.
• Infrastructure: 13 Centers of Excellence (CoEs) were designated to deliver diagnostics, treatment, and care for rare diseases.
• Regulation: A fast-track 90-day approval mechanism for rare disease drug applications was announced in 2024.

Yet multiple challenges persist:

1. Delayed diagnosis: Many patients wait 10–20 years before identification, due to limited newborn screening, minimal genetic counseling, and rural inequities.
2. Funding shortfalls: Only four of 12 CoEs utilized NPRD funds in recent years.
3. Few regulatory incentives: India offers neither exclusivity nor structured tax credits, leaving limited industry participation.
4. Fragmented registries: NRROID and CTRI remain underdeveloped and lack global interoperability.
5. Reliance on philanthropy: Corporate Social Responsibility (CSR) and crowdfunding substitute for national insurance-based support.

Supporting Context

Comparative Analysis
The table below compares how the various regulatory systems impact research, innovation, social equity, and drug development in rare diseases across India, the US, and the EU. The difference is clear: where the US and EU have predictable incentives, structured funding, and fast-track reviews, India’s ecosystem remains fragmented and under-resourced.

Contrasting Viewpoints
Driven by support from novel policies and financial aid schemes, India shows promising results in rare disease treatment and care, but still lacks a strong ecosystem to accelerate rare disease research.

• Pro-indigenous innovation: India aims to deliver cost-effective drugs, as is evident in the domestic production of eliglustat for Gaucher’s disease, slashing annual treatment costs by ~95%.
• Pro-harmonization: Experts argue that India must establish an office like the FDA’s Office of Orphan Product Development (OOPD) to streamline trials and attract global investment.

Digital Health and Innovation

India is experimenting with telemedicine and in silico alternatives to animal testing, but lacks a framework for integrating AI or RWE into approvals. By contrast, the FDA and EMA actively incorporate model-informed drug development and AI-based tools into regulatory review. This will accelerate orphan drug clinical research in India, where securing appropriate and timely approval for animal studies faces various regulatory and operational bottlenecks.

The US Cystic Fibrosis Foundation registry shows how comprehensive patient registries can reduce trial timelines dramatically. India’s rare disease registries lag in terms of completeness and data standards, limiting their visibility in global collaborative research.

Broader Implications

1. Human impact
   Patients without timely care face progressive disability, mental health challenges, and limited work capacity. Indian disability law recognizes some conditions but rarely translates into adequate social support. Families shoulder crippling out-of-pocket costs.
2. Equity implications
   When ~70 million Indian patients are invisible in registries, the global rare disease picture is skewed toward high-income regions, leaving neglected conditions under-researched.
3. Industry consequences
   If India expands registries and joins RWE pilots like those in Europe, companies could run lower-cost trials in India’s large patient population, incentivizing faster and cheaper domestic therapies.
4. System readiness
   Greater capacity at CoEs, integration of newborn screening programs like Rashtriya Bal Swasthya Karyakram (RBSK), and coordinated state-center implementation will be critical to reducing disparities.

Call to Action
To move from lagging to leading in global rare disease care, India should act decisively in the next 3–5 years:

1. Establish a dedicated orphan drug pathway with designations, exclusivity, tax credits, and formalized accelerated review, modeled on US/EU best practices.
2. Expand registries like NRROID and improve CTRI to be globally compliant (ICTRP, ClinicalTrials.gov).
3. Integrate digital health and in silico tools into both trial management and regulatory decision-making.
4. Secure sustainable financing: shift from ad hoc philanthropy to structured national funds and insurance coverage.
5. Build capacity at primary care levels: train physicians, genetic counselors, and frontline workers to detect and refer rare cases early.
6. Develop a working-capacity framework (like EU ICF models) to account for social and economic impacts of rare conditions.

Bottom line: India’s policies must evolve rapidly to align with global best practices and foster cross-border collaborations while retaining local affordability solutions. Otherwise, millions will remain invisible and underserved.

Conclusion

Rare disease regulation is no longer a niche conversation. It is a matter of global health equity. The US and EU have shown what consistent incentives, robust registries, and accelerated reviews can deliver. India has taken first steps, but it now requires bold, comprehensive reforms to protect its patients, attract innovation, and participate fully in global rare disease research.

The coming years will define the future: Will India remain on the margins, or will it lead with reforms scaled to its population, aligned with global strategies, and centered on patients? The lives—and livelihoods—of tens of millions hang in the balance.