EMA-FDA QbD Pilot Program Report

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

In March 2011, the European Medicines Agency (EMA) and the United States Food and Drug Administration (US FDA) launched a joint pilot program for the parallel assessment of applications containing Quality by Design (QbD) elements. The intended purpose of this program was to facilitate the consistent implementation of QbD concepts of ICH Q8, Q9 and Q10 documents and to harmonize regulatory decisions across the two regions. The pilot was initially planned for three years and extended until April 2016.

The purpose of the pilot was to share knowledge, support consistent implementation of quality by design concepts in international guidelines and to promote the availability of medicines of consistent quality throughout the EU and the US.

On 19th April the final EMA-FDA QbD pilot program report was published. During the pilot period, the agencies received 16 requests to participate. One submission was rejected because the approach presented was not limited to QbD applications. Another application was not reviewed because it was never filed by the applicant. In total, 14 submissions have been evaluated:

• two Marketing Authorisation Applications (MAA)/New Drug Applications (NDA),
• three variation/supplements, and
• nine scientific advice applications.

Among these was

• the first continuous manufacturing (CM) based application submitted to both agencies (including real-time release testing (RTRT) methods and good manufacturing practice (GMP) considerations for RTRT),
• a post approval supplement that included a broad based post-approval change management plan/comparability protocol.

Additionally, the EMA and the FDA have published three questions-and-answers documents on lessons learned and to clarify a number of details (these also addressed comments from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), which participated as observer):

• EMA-FDA pilot program for parallel assessment of Quality-by-Design applications: lessons learnt and Q&A resulting from the first parallel assessment (published on August 20, 2013). It included the following topics: Quality target product profile (QTPP) and critical quality attributes (CQA), Criticality, Level of detail in manufacturing process descriptions, and QbD for analytical methods;
• FDA-EMA Questions and Answers on Design Space Verification (published on October 24, 2013), that included definition, presentation, justification (including potential scale-up effects) and verification of design spaces both for active substances and finished products;
• FDA-EMA Questions and answers on level of detail in the regulatory submissions (published on December 10, 2014) included the following topics: Level of detail in the dossier regarding Risk Assessment (RA), Level of detail in the dossier regarding Design of Experiments (DOE) and Design Space.

The report concludes that both agencies are strongly aligned on the implementation of QbD concepts included in the ICH Q8, Q9 and Q10 guidelines and that potential future joint activities will have a focus on continuous manufacturing, emerging technologies, and expedited/accelerated assessments.

For more information please see the final Report from the EMA-FDA QbD pilot program.