Philadelphia (July 24)—The US Food and Drug Administration’s Pharmaceutical Quality for the 21st Century initiative represents a crucial change in the regulation of pharmaceutical manufacturing and product quality. Moheb Nasr, director of the Office of New Drug Quality Assessment (ONDQA), Center for Drug Evaluation and Research at FDA, addressed the agency’s history and progress in moving to a science- and risk-based approach to regulation at the Pharmaceutical Technology Annual Conference^*.

“The current status of pharmaceutical manufacturing shows certain challenges,” explained Nasr. He pointed out that although current pharmaceutical manufacturing is adequate and in sufficient quality, it is not as innovative and efficient as other high-technology industries, has high costs, can suffer from a lack of coordination or integration among key business units such as research and development, manufacturing, quality, and regulatory affairs, and operates at times in an overly conservative regulatory framework.

Seeking to address those challenges, during the past three years, FDA put forth a series of key initiatives beginning with FDA’s Critical Path Initiative and followed by Pharmaceutical CGMPs for the 21st Century:A Risk-Based Approach, the Process Analytical Technology (PAT) guidance, ONDQA’s Pharmaceutical Quality Assessment System and CMC Pilot Program, and Quality by Design. The process continued with International Conference on Harmonization and the finalization of ICH Q8 and ICH Q9. Other key initiatives include the Question-based Review (QbR) Process and most recently in 2007, the Quality Initiatives Workshop with FDA, the American Associaiton of Pharmaceutical Scientists, and the International Society for Pharmaceutical Engineering.

A key component of these actions was the creation of PQAS. PQAS was established to encourage the pharmaeutical industry to apply QbD principles to drug development. It promotes the science and risk-based approach to regulation as described in the Pharmaceutical Quality Initiative for the 21st Century.

“The system relies on submission of knowledge-rich, scientific information that demonstrates product and process understanding,” said Nasr. “It encourages regulatory flexibility based on enhanced product knowledge and process understanding.”

QbD is a crucial part of the tranformation urged by FDA. “QbD is a scientific, risk-based, holistic and proactive approach to pharmaceutical development,” said Nasr. “It is a deliberate design effort from product conception through commercialization and provides a full understanding of how product attributes and process relate to product performance.”

To facilitate the use of understanding of QbD, ONDQA established a CMC Pilot Program that allows participating firms an opportunity to submit chemistry, manufacturing, and controls (CMC) information demonstrating QbD principles, product knowledge, and process understanding. In turn, it enables FDA to evaluate a comprehensive quality overall summary and new concepts and approaches such as QbD, design space, and real-time release. To date, nine original new drug applications (NDA) and two supplemental NDAs have been accepted as part of the program.