US FDA-EMA QbD Harmonisation Pilot Progressing Slowly

The parallel QbD (Quality by Design) application review program by the US FDA and EMA is slowly revealing the differences between the two agencies but will never result in identical assessments or outcomes, experts said.

If nothing else, the pilot increased discussions between the two agencies, though both said the process of teleconferencing nearly every two weeks to discuss ongoing applications and to meet their respective review timelines was resource intensive.

We’re not there yet but we’re getting there,” Elaine Morefield, PhD, of the FDA’s office of new drug quality assessment said. She noted that the pilot initially sought four applications by March 2014 and has so far received one NDA (new drug application) and two IND (investigational new drug) applications.

Pfizer and Vertex Pharmaceuticals submitted applications and representatives from both companies seemed positive on the idea of the pilot but the amount of detail requested by the EMA was significantly more than what the FDA wanted.

Pfizer’s Xeljanz (tofacitinib), a treatment for rheumatoid arthritis, was the first drug to be approved under the pilot. John Groskoph, senior director of Global CMC at Pfizer, said Tuesday at DIA’s 49th annual meeting in Boston that after submitting the application, the company received about 35 questions from the FDA, and 100 from the EMA, though 19 were identical for both agencies.

Groskoph said there were “some missed opportunities” with their first application, though Pfizer would be willing to go through the process again.

Morefield said she understood the disappointment but that this is just the baseline for more collaboration between agencies, which basically wanted to see the differences between their questions.

FDA-EMA Understandings and Differences

Both agencies agreed that more work needs to be done to address NIR, risk assessment details and design space development. More uniformity on process validation, which the FDA only says is necessary for sterile products, and process descriptions are also needed for more harmonization, Morefield said.

One of the areas where the EMA and FDA see eye to eye is on the level of detail they reviewed in applicants’ manufacturing process descriptions, Evdokia Korakianiti, PhD, head of the chemicals section of the EMA, said.

Morefield elaborated that in the area of continuous manufacturing, both agencies agreed on the traceability of input materials, the idea of a “steady state of operation,” the handling of non-conforming material during the start-up, shut down and process upset phases, as well as the definition of a batch, character and quality uniformity.

Korakianiti said guidance from the EMA on best practices for QbD will be published before September.

Requests to participate in the parallel review pilot program are still being accepted through March 2014.