Navigating advanced therapy development for rare diseases is challenging from many perspectives and requires a customised development strategy. Advanced therapies - referred to as advanced therapy medicinal products (ATMPs) in the EU and as cell and gene therapies (CGT) in the US – are medicinal products based on genes, tissues or cells. Advanced therapies are especially promising for the long-term treatment or even durable solution of the underlying - often genetic - cause of rare diseases. However, compounding challenges of manufacturing and clinical development necessitate a regulatory strategy that diverges from traditional pathways. This blog provides a regulatory roadmap that identifies relevant meetings, applications and resources that can help an advanced therapy for rare disease achieve approval in the US and EU.

Sponsors should engage throughout clinical trial development with the relevant regulatory bodies to navigate the unique challenges and opportunities that come with the development of advanced therapies for rare disease. During the preclinical and clinical stages of development, meetings with regulatory agencies can guide trial design and accelerate development. For example, the US and EU offer expert scientific consultation on protocol design for rare disease advanced therapies during preclinical development. This scientific advisory protocol assistance can be conducted simultaneously, with advisors from the European Medicines Agency and FDA both present. The list of relevant meetings sponsors can have with regulatory bodies in the US and EU to ensure streamlined clinical development are as follows:


  • Innovative Task Force Meeting (EU) – advice on regulatory, technical and scientific issues specific to innovative medicine development
  • CATT (US) – addresses regulatory challenges associated with development of advanced technologies for manufacturing and testing products
  • INTERACT (US) – preliminary consultation on early stage development of investigational products


  • Scientific advisory protocol assistance (US, EU) – consultation on protocol design and considerations for clinical development
  • Pre-IND (US) – feedback informs the preparation of the investigational new drug (IND) application to authorise clinical development
  • SPA (US) – feedback helps determine whether a clinical trial could lead to market authorisation


  • EOP I and/or EOP 2 (US) – feedback on whether an ongoing trial is sufficient for marketing authorisation or accelerated approval
  • Pre-BLA (US) – consultation on technical issues with submission of biologics licence application (BLA) to streamline upcoming review 

In addition to regulatory meetings, there are a number of certifications, designations and classifications that are likely to be relevant for rare disease advanced therapies. These applications can help to ensure your clinical development is appropriately resourced, that your therapeutic is appropriately expedited and that the challenges associated with rare disease and advanced therapies are accounted for during review of clinical trial authorisation and market authorisation submissions. The list of applications often relevant for rare disease advanced therapies are as follows:


  • Orphan drug designation (EU, US) - provides government assistance for development of drugs that treat exceedingly uncommon conditions, which may otherwise not be a commercially viable propoisition
  • ATMP classification (EU) - helps developers to clarify the development path and the applicable regulatory framework based on the advanced therapies proposed mechanism of action
  • PRIME designation (EU) - provides accelerated pathway for clinical development, where appropriate
  • Fast track designation (US) -  provides accelerated pathway for clinical development, where appropriate


  • RMAT designation (US)  - provides accelerated pathway for regenerative medicines
  • ATMP certification (EU) - determines whether additional studies are needed for marketing authorisation approval and streamlines review process
  • Priority Review (US) - accelerated review of market authorisation application (MAA)
  • Rolling Review (US) - allows for staggered submission of market authorisation application

Sponsors of rare disease advanced therapies may also need to include additional information in their clinical trial (IND in the US; CTA in the EU) and marketing approval applications (BLA in the US; MAA in the EU). For gene therapies developed in the EU, an environmental risk assessment and genetically modified organism summary are needed for clinical trial application approval. In addition, paediatric drug development plans are a legal requirement for all new drugs in the US and EU, depending on the ages of the intended participants, although the US can make exemptions for orphan designated products.

In this fast-moving area, support from experts in clinical trial development of rare disease advanced therapies will ensure that your therapeutic development and regulatory strategy are sound.

For more information on unlocking the potential of advanced therapies developed for rare diseases, read our whitepaper and review our blog about clinical development challenges.