Industry, FDA Officials Sing Same Tune: Harmonize Quality by Design

Singing the same tune officials with FDA and industry trumpet harmonized QbD.

An industry representative and an FDA official called at a meeting in July for the International Conference on Harmonization to develop a harmonized quality-by-design model for submitting quality information for new drug applications in the Common Technical Document.

The question of where QbD information should be placed in the ICH Common Technical Document also generated discussion at the July 17 Well Characterized Biotechnology Pharmaceutical CMC strategy forum on QbD for biopharmaceuticals, sponsored by the California Separation Science Society at the National Institutes of Health in Bethesda, Md.

There appeared to be a consensus that the best place for placing this information would be in Module 2 in the Quality Overall Summary, even though some elements could also appear in Module 3, the quality section.

Industry participants at the afternoon panel were discussing the implications of QbD for regulatory filings and approval. The panel also discussed the QbD framework, with a focus on large-molecule products.

CDER Office of Biotechnology Products Director Steven Kozlowski noted that ICH is the best vehicle for harmonizing QbD. "Implementation of QbD is where the next wave of harmonization needs to be."

John Towns of Eli Lilly in Indianapolis, Ind., concurred. "We would like to do global studies so we can submit a global application. The future CTD may not be as friendly as we hoped in providing QbD."

Towns told "The Gold Sheet" that "the CTD does not lend itself to putting in QbD." Instead, QbD is "chopped up into different sections" of the CTD.

Nonetheless, Eli Lilly, he said, has embraced the QbD concept in both its small-molecule as well as large-molecule drug development programs.

Kozlowski agreed that QbD could foreseeably be placed in Module 2 of the Quality Overall Summary under the Justification of Specifications section.

Towns indicated Eli Lilly has fully embraced the QbD concept because it is a more efficient approach for designing quality systems. "Baby steps [for using the QbD option] is not an option. We did this because it was more efficient."

The QbD concept also received endorsement from an FDA reviewer who noted that QbD reviews are "a lot simpler" than reviews conducted under GMPs.

"A review of design of experiments makes understanding the application much easier. It makes it easier to understand why things are done. As a reviewer I understand why things are done. As a reviewer I understand what you did. Overall, it is a hugely different application. It is not like voodoo science."

Although ICH supports QbD in its Q8, Q9, and Q10 guidelines, Towns suggested that from a practical standpoint, in order for this concept to be applied, it must be included in the CTD for global applications.

In other areas, Rohin Mhatre of Biogen Idec, Cambridge, Mass., said that the process of QbD filings "does not seem all that different" from current GMP practices.

Kozlowski responded that "it's not so much that it is new. It is a marketing term for an idea that has been around. By taking risk assessment and formalizing it, it forces more interactions within your company."

Kozlowski further observed that firms that intend to adopt QbD must learn to let go of the former systems. "It's a culture change."

Yet John Dougherty of Eli Lilly pointed out that "with inspections, we're following the QbD model. So we're doing things that do not follow on the [GMP] checklist….Yet inspectors are still looking at GMPs, not QbD."

- Joanne S. Eglovitch ([email protected])