Proceedings: DIA 2018 Global Annual Meeting

EMA/FDA Question Time

Chris M. Slawecki
DIA Senior Digital Copy Editor


MA and FDA work together, for patients in their own jurisdictions and around the world, through a unique bilateral cooperative framework. The “EMA/FDA Question Time” DIAmond session gave leadership from these agencies the opportunity to present their current projects in four key areas, and gave attendees the opportunity to ask them questions about these projects. This session was hosted by Tânia Teixeira, who serves as EMA Liaison Official to the FDA; and by Sandra Kweder, FDA Liaison to the EMA. “We’re embedded in each other’s agencies to further this communication and collaboration,” Kweder explained. “My job is to explain you – explain us – to Europe, and Tania does the same thing [to the US].”

Key Takeaways

  • Legal confidentiality agreements allow both agencies to work with non-public information provided in confidence, share non-public pre-decision information, and share draft guidances and/or legislation.
  • Most of their collaboration comes through working groups, or “clusters”:
    • Current cluster topics include advanced therapies/regenerative medicine, biosimilars, API inspections, preclinical oncology, and pharmacogenomics.
    • Some clusters are very involved in the development of specific product types, such as biomarkers, orphan medicines, and pediatric medicines.
    • Multinational clusters include Health Canada, PMDA, SwissMedic, and/or other regulatory bodies.
  • Product evaluation and surveillance are a large part of their joint charter: Their joint GCP inspection initiative allows for collaborative GCP inspections and sharing inspection information; their 2017 Mutual Recognition Agreement allows them to share GMP surveillance inspection data.
  • Each agency’s increased focus on early engagement in development planning often leads to the recommendation that the sponsor seek parallel EMA-FDA scientific advice.
  • When EMA and FDA reach different conclusions, they discuss these differences and why they have occurred.

Sudip Parikh discusses regulatory collaboration with Sandra Kweder and Peter Marks.

Product Quality

In Europe, quality and CMC (chemistry, manufacturing, and controls) are now seen as part of the critical path to early access. EMA’s PRIME (PRIority MEdicines) scheme maximizes existing regulatory tools such as scientific advice and accelerated assessment to further support development of medicines that target unmet medical needs. Much of EMA’s effort in this area has been through providing scientific advice to small- and medium-sized enterprises during development planning and kickoff meetings for biologic products. PRIME has received nearly 180 applications, and to date 36 products have been approved via PRIME.

EMA PRIME generally parallels the FDA Breakthrough Therapy Designation. Breakthrough Therapy expedites the development and review of drugs that are intended to treat a serious condition through extensive Agency guidance (as early as phase 1) on efficient drug design and development, and the opportunity for Fast Track approval designation. Fifty products have been approved as Breakthrough Therapies since the program’s 2012 inception.

Quality and CMC are critical elements of both of these pathways and require due attention by sponsors as well as regulators. “Quality is not a compromise,” Randazzo said. “We will work with you on how we can do it faster and better.”

Data Transparency

The goal of clinical data publication, Henry-Eude explained, is to be transparent about what the regulations are assessing, and to connect to the data being assessed. “EMA has certainly been the leader here,” allowed Witt, even if many shared challenges remain.

For example, different legal directives result in different redaction rules in the US compared to Europe. Different redaction rules mean that different information reaches the public in the US than reaches the public in Europe; the scope and reach of the internet across international borders complicates data transparency. Both agencies would welcome more alignment on this issue.

Agnes Saint-Raymond and Lynne Yao discuss pediatric medicine while Kristina Larsson and other panelists listen.

Session Chairs: Tânia Teixeira, EMA Liaison Official to FDA; Sandra L. Kweder, FDA Liaison to the EMA

Product Quality: Peter Richardson, Office of Quality, EMA, EU; Giuseppe Randazzo, Office of Pharmaceutical Quality, CDER

Data Transparency: Anne-Sophie Henry-Eude, Documents Access and Publication Services, EMA; Ann Witt: CDER

Pediatrics: Agnes Saint-Raymond, Portfolio Board, International Affairs, EMA; Lynne Yao, Division of Pediatrics and Maternal Health, CDER

Rare Disease Product Development: Kristina Larson, Orphan Medicines, EMA; Lucas Kempf, Rare Diseases Program, CDER


The primary force behind pediatric drug development in Europe is the Pediatric Regulation which came into force in January 2007 with the objective of facilitating the development and availability of medicines for children aged 0 to 17 years. According to the State of Paediatric Medicines in the EU report issued in January 2017, 150 new pediatric products were approved, and the number of pediatric clinical trials increased in Europe, as a result of its implementation. “I think the regulation has delivered after ten years,” said Saint-Raymond. “Now it is time to reflect on how it may be improved.”

The RACE Act and 21st Century Cures Act both focused on unmet pediatric need in the US. The RACE (Research to Accelerate Cures and Equity) for Children Act of 2017 amends the Pediatric Research Equity Act to require sponsors of certain drugs and biological products for adult cancer to assess the use of their medications in pediatric populations if there is reason to believe the medication would have a meaningful therapeutic benefit over existing therapies for pediatric cancer patients.

21st Century Cures includes language specifically directing the National Institutes of Health to fulfill the requirements of the National Pediatric Research Network Act, which became law in November 2013 but has not yet been implemented, to speed the development of a new network of consortia focused on pediatric research.

Moderators and counterparts Sandra Kweder and Tânia Teixeira listen to panel discussion.

Despite these and other efforts, the contrast in drug development in adults compared to children, especially in oncology, remains dramatic in both the EU and US.

Rare Disease Product Development

In the EU, 83 percent of the products approved via PRIME are for rare diseases; in the US, more than 60 percent of Breakthrough Therapy approvals are for rare diseases. Because of so many complicated issues in this disease space, the EMA/FDA Rare Disease Cluster often meets to discuss general topics and specific product reviews. This Cluster provides a lot of “up front support” in the IND phase to sponsors developing rare disease products. “There’s no room for trial and error in rare disease,” Kempf explained. “You have to be smart from the outset.”

Do EMA and FDA Define “Unmet Medical Need” the Same Way?

They both have definitions, and the wording is generally similar between them. But there can be (and have been) differences in interpreting these definitions in the context of developing a specific product. The Pediatric Regulation ten-year report elevates the need for better definition of unmet medical need. Regulators recognize that they must get this definition right, so that drug developers can get it right, too.