FDA encourages a risk-based regulatory approach where relevant regulatory policies and procedures are modified to accommodate the most current level of scientific knowledge. The change would focus on increasing the level of scientific understanding of how formulation and manufacturing process factors affect product quality and performance. More focus in the development stage is needed to design the capability of process-control strategies to prevent or mitigate the risk of producing a poor quality product.

This step is much more about a new philosophy and operational culture than it is about new standard operating procedures and a new quality manual. There may be a need to vastly improve and retool cross-functional and cross-departmental communication and coordination. A silo-based approach simply will not work. Every part of the organization that touches on the product life cycle will need to operate in a much more integrated way. Most of the advances that have occurred, and are anticipated to occur, are bringing the development, manufacturing, quality assurance, and information and knowledge-management functions so closely together that these four areas should be coordinated in an integrated manner. There may be a need to also include some of the not-so-obvious players such as regulatory, marketing, product surveillance, senior management, and so forth. Management responsibility and involvement is absolutely critical to the quality system. The current business model based on speed-to-market must strike a different balance and approach with more emphasis on doing it right.

Risk management

There is a practical relationship between quality and today's business realities (profit and cost-of-goods) where business objectives can be used to drive quality-system improvements. An understanding is also needed of the basic operational and scientific principles behind quality systems, quality by design, and PAT. There are core principles common to them all:

• Scientific knowledge
• Design for control
• Oversight
• Feedback
• Adjustment
• Simple logic.

Table I: Hazard control concepts.

The overarching context for the core principles are the application of hazard control—an umbrella term that broadly describes the various risk-based concepts that FDA has been discussing (see Figure 4). Hazard control includes:

• Risk assessment
• Risk evaluation
• Risk management
• Risk mitigation.