Drug Development for Rare Diseases

Orphan Drugs Among Newly Approved Medicines

Each year, new medicines containing novel active substances are authorised and launched on the German market. In 2025, 37 medicines with new active substances were introduced, alongside 23 label extensions, 11 new dosage forms and four new active substance combinations. Around two thirds of the 37 newly approved drug products were developed to treat rare diseases, commonly referred to as orphan diseases.¹
A disease is classified as rare in the European Union when it affects no more than five in every 10,000 people. Fourteen of the newly approved medicines received orphan drug status.² This designation is granted to drug products intended for rare diseases when they offer a significant benefit over existing treatment options for patients, or for a specific subgroup of patients.

One example of such a rare disease is molybdenum cofactor deficiency. Across the entire European Union, only around 450 patients are affected by this condition.² Such extremely small patient populations not only enhance difficulty for research into rare diseases, but genetic variations in disease manifestation can further complicate the development of effective therapies. As a result, orphan drugs often require highly tailored formulations and dosage strengths designed to meet the specific needs of individual patients.

The Orphan Designation

To encourage the development of treatments for rare diseases, the European regulatory framework provides several incentives through the orphan designation. These measures are designed to reduce the financial risks associated with both the development process and the subsequent commercialisation of orphan medicines. Upon application, the European Medicines Agency (EMA) may grant a medicinal product orphan designation if it fulfils the relevant criteria. This status can provide access to regulatory and scientific support programs as well as reduced fees for certain regulatory activities.

In addition, orphan medicinal products benefit from ten years of market exclusivity in the European Union, extending beyond the protection granted to newly authorised drug products and making it more difficult for competing products to enter the market during this period.³˒⁴
While these incentives help reduce financial risks and improve the commercial attractiveness of orphan drug development, they do not diminish the scientific, technical and operational challenges associated with bringing a product to market. In particular, the stringent GMP requirements governing pharmaceutical development and manufacturing remain fully applicable to orphan medicinal products, just as they do for any other medicinal product.

Challenges in Orphan Drug Development

Like all medicines authorised in the European Union, orphan drugs must progress through active pharmaceutical ingredient (API) development, formulation development, preclinical studies and clinical trials before reaching patients. However, the development of orphan drugs presents several unique challenges. Clinical development is often complicated by the limited availability of patients, requiring studies to be conducted with small cohorts and restricted datasets. At the same time, the same rigorous standards of quality, safety and efficacy apply as for drug products targeting larger patient populations.Significant challenges also arise on the Chemistry, Manufacturing and Controls (CMC) side. Commercial demand is frequently low, meaning that only small development batches, clinical batches or commercial production batches are required.

However, many industrial manufacturing facilities are designed for substantially larger production volumes. As a result, manufacturing processes often need to be adapted, scaled down or partially carried out manually. These manual or semi-manual processing steps can be more difficult to standardise and validate than highly automated manufacturing operations. Furthermore, fixed costs associated with analytical testing, stability studies, equipment qualification, process validation, documentation and regulatory activities must be spread across comparatively small production volumes.

In addition, orphan drugs are disproportionately associated with complex dosage forms, highly potent compounds, patient-specific dosing requirements and specialised storage or distribution conditions. Consequently, the development effort per treated patient is often significantly greater than for drug products developed for larger therapeutic indications. For this reason, flexible development and manufacturing strategies are essential to efficiently integrate scientific, technological and regulatory requirements throughout the product lifecycle.

HWI as a Trusted Partner for Orphan Drug Development

The unique requirements of orphan drugs frequently demand development and manufacturing approaches that differ considerably from those used for conventional drug products targeting large markets. Success depends less on highly standardised mass-production processes and more on scientific expertise, operational flexibility and the ability to develop tailored solutions for individual projects. This is precisely where HWI's strengths lie. Through the close integration of pharmaceutical development, GMP manufacturing, analytical services, quality control and regulatory support, HWI provides comprehensive project support throughout the entire development journey.

Clients particularly benefit from HWI's agility when working with small batch sizes, complex dosage forms and highly potent active substances. While large manufacturing facilities are often optimised for standardised, high-volume production, HWI's flexible manufacturing infrastructure enables the efficient production of small batches and the implementation of patient-specific requirements where necessary. Highly potent compounds can be handled safely using HWI's established containment concepts and experienced specialist teams. In addition, HWI's broad range of development and manufacturing technologies makes it possible to process and formulate even highly complex active substances.

Close and transparent communication with clients ensures efficient project execution, while extensive analytical expertise supports the early identification and understanding of critical quality attributes. This enables potential development risks to be addressed at an early stage, reducing project uncertainty and supporting more efficient development pathways. Drawing on many years of experience, HWI also provides valuable support in regulatory interactions and communication with health authorities. The result is the development and manufacture of safe, high-quality, GMP-compliant medicinal products specifically tailored to the needs of rare diseases and small patient populations.

You can find out more about our drug development services here: CDMO services

Source:
[1] vfa. The Research-Based Pharmaceutical Companies "Medicinal Products with New Active Substances Introduced in Germany in 2025.”
[2] Neue Medikamente in Deutschland: Innovationsbilanz 2025, accessed 18.08.2026, 08:22.
[3] BfArM - Arzneimittel für seltene Erkrankungen, accessed 18.08.2026
[4] Orphan designation: Overview | European Medicines Agency (EMA), accessed 18.08.2026