Quality by Design for FDA Approval: Building Control vs. Inspection

In 2011, the FDA implemented a Quality by Design (QbD) pilot program to support their review and approval process. After gathering several years worth of research, the FDA decided to push forward with a QbD approach to evaluate the manufacturing processes used by pharmaceutical companies.

The central idea is to focus on improving control in the preliminary and beginning stages of manufacturing, rather than waiting until the inspection stage for a reactionary evaluation.

Manufacturers that embed QbD into their manufacturing process and demonstrate the ability to consistently follow the processes are more likely to receive FDA approval for new applications. They will also benefit from expedited drug applications because they will be aligned with the approach the FDA considers the best option for manufacturing safe, reliable drugs for the end user.

Why Build In Control over Inspection?

QbD in pharmaceuticals boils down to a simple comparison of “why” (control) versus “what” (inspection). Manufacturers that build in the “what” focus on the creation and inspection of rules and procedures. However, if your employees do not understand the “why,” there is possibility for quality, design, and production flaws.

Building in the “why” ensures that employees understand their role in the manufacturing process, the triggers related to certain actions, and how their actions affect quality. If your team is trained to only focus on following the rules and procedures (what), they will not be as focused on the critical element of quality.

Consider these characteristics of an integrated manufacturing process that aligns with the expectations of the FDA:

  • Control specs and limits that truly reflect output quality and safety.
  • A process that guarantees the consistency of product and process outputs.
  • Definitions of how the process will operate through the monitoring of critical characteristics of that process.

What Does Building in Control Look Like?

The key to executing a manufacturing process that focuses on quality is the control strategy (control plan). The control strategy should align with these points of emphasis:

  • Quality control must be built into each process step rather than relying on inspection.
  • Quality systems are integrated into the data systems.
  • Living quantitative risk assessment process rather than a one-time event that drives the controls and verification methods.
  • Implement a quality operating system, rather than a quality management system

This paradigm shifts the focus from interpretation of the regulations strictly to implementing the intent of the regulations into process control and quality.

The AMLS Way to Support a Quality Operating System

AM Life Science (AMLS) has developed a unique approach to QbD called Early Quality Integration that helps clients align with the FDA approval requirements.

Mainly, we focus on delivering the required verification for CQV while each element of the construction and installation is being conducted, rather than waiting for the turn-over to CQV phase.  This assures that work meets all requirements before being designated as complete, resulting in significant reduction in rework, cost and schedule. It also provides a focus on the “why” of understanding the living process needs, how processes are controlled, and ensuring that each step contributes to a product that consistently meets specifications.

Our approach also supports the “what” and the “how” of following the applicable standards, mapping out processes to match the regulatory requirements, conducting gap analysis, and collaborating with others throughout the process.

To learn more about how we follow and apply QbD in each project to support FDA approval for pharmaceutical companies, we invite you to download our whitepaper on Early Quality Integration.