FDA Perspectives: Understanding Challenges to Quality by Design

Directors from FDA's Center for Drug Evaluation and Research summarize findings in an FDA-commissioned report on QbD and propose actions the agency can take to encourage full-scale QbD implementation.
Sep 01, 2011

To understand the challenges and opportunities associated with implementing quality by design (QbD), FDA contracted an independent consultant to evaluate current industry adoption of QbD. This article summarizes those findings and proposes actions FDA can take to encourage full-scale QbD implementation.

In 2004, FDA released its final report on "Pharmaceutical Quality for the 21st Century: A Risk-Based Approach." The purpose of the initiative, which was launched in 2002, was to encourage innovation and implementation of new manufacturing technologies, focus the agency's resources on those areas of pharmaceutical manufacturing considered to pose the most risk, and improve on the consistency and predictability of the agency's work in ensuring drug quality and safety. In the 2004 report, FDA outlined its initiation of quality by design (QbD)—a science- and risk-based approach that begins with predefined objectives for meeting the desired clinical performance and emphasizes product and process understanding and process control.

Working with regulators in the European Union (the European Medicines Agency and European Competent Authorities) and Japan, FDA has been instrumental in furthering QbD objectives through the International Conference on Harmonization (ICH), and industry has made progress in implementing QbD in terms of its corporate culture, operations, and quality systems. But, as is the case with many new endeavors, challenges still exist that inhibit full-scale implementation.

In an effort to understand these challenges and identify opportunities for adoption, FDA contracted an independent consultant to objectively evaluate and develop a fact-based consensus view on the state of QbD adoption. The team got input from several sources—literature research, database searches, and interviews with industry leaders—to gauge industry's current perspectives on QbD and its level of adoption. This article summarizes the consultant's findings, to include key adoption challenges and implementation issues, as well as actions that FDA can take to encourage full-scale implementation and ultimately ensure the production of high-quality products.

Evolution of quality by design

QbD has continued to gain momentum during the past several years. One of the most striking factors has been an increase in the codification and practice of QbD in a standardized basis. More and more companies are experimenting with and using the concept, as well as developing mechanisms to support it. That being said, companies are at very different levels of maturity in terms of QbD adoption. Four levels of maturity were identified in the report.

Table I: Level of maturity and drug type of examined companies.
The first level of maturity, novice, is defined as a company that is skeptical about the value of QbD. The company uses conventional development practices and has no QbD platforming. The second level, pilot, defines a company that is trying QbD, but is still uncertain about the initiative's potential value. This company tends to apply QbD to a small subset of projects and processes and has implemented limited or no QbD platforming. The third level, rollout, is a company that is convinced about QbD's impact and is beginning to see some of the benefits. This company uses QbD techniques regularly, but not universally, and may engage in some life-cycle management with integrated QbD platform and network strategy. Finally, the fourth level, categorized as fully implemented, defines a company that is completely convinced about QbD's positive impact and has seen the benefits. This company uses QbD in almost all development programs. It also has a systematic, comprehensive review and redesign of in-line products. Table I illustrates, by drug type, the level of maturity of those companies that were examined.