EMA-FDA QbD Pilot Program Led to Further Harmonization

The European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have wrapped up a joint pilot program assessing applications containing Quality by Design (QbD) elements that led to further hamornization of concepts introduced through the International Council for Harmonisation (ICH).

Background

The joint pilot program, initially launched in March 2011 for three years, was extended for two more years in 2014 to facilitate further harmonization of pertinent QbD-related topics and officially concluded in April 2016, according to a report released Wednesday.

QbD-related principles are primarily contained within ICH’s Q8, Q9 and Q10 guidelines, and assessors and reviewers from the US and EU exchanged their views on the implementation of ICH concepts and relevant regulatory requirements using actual applications that requested participation into the program.

Based on the learnings from the pilot, FDA and EMA jointly developed and published three sets of Question and Answer (Q&A) documents in 2013 and 2014, which also addressed comments from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), which participated as an observer.

Results

In total, two Marketing Authorisation Applications (MAA)/New Drug Applications (NDA) (one of which was assessed under the parallel assessment pathway), three variation/supplements and nine scientific advice applications were evaluated under this program.

According to the report, the FDA-EMA pilot provided the agencies an opportunity to harmonize regulatory expectations for two precedent-setting applications reviewed under the consultative advice pathway:

• The first continuous manufacturing based application submitted to both agencies, which allowed for the harmonization of batch definition; control of excipients; material traceability; strategy for segregation of nonconforming material; real-time release testing (RTRT) methods and prediction models; and good manufacturing practice (GMP) considerations for RTRT, validation strategy, models, and control strategy.
• A post approval supplement that included a post-approval change management plan/comparability protocol. “Both agencies were harmonized on the expected level of detail in the protocol and considerations for implementation of a risk based approach to evaluate the changes proposed in the protocol,” the report says.

“Overall, it is concluded that, on the basis of the applications submitted for the pilot, there is solid alignment between both Agencies regarding the implementation of multiple ICH Q8, Q9 and Q10 concepts,” the regulators said.

Moving forward, EMA and FDA will explore potential joint activities with a specific focus on continuous manufacturing, additional emerging technologies and expedited/accelerated assessments, in addition to hosting experts from each other’s organizations to facilitate dialogue and explore more opportunities.

Report from the EMA-FDA QbD pilot program

EMA on Quality by Design