CHANGES IN JOB FOCUS

This holistic way of operating will mean some fundamental changes in focus by staff in key functions. For example, consider the age-old disjunction between development and manufacturing. It's often been said that development personnel "threw their creations over the wall" to manufacturing who would say, in effect, "thanks, we'll take it from here." GMPs meant simply following the rules established during validation and then performing quality assurance (QA) to make sure each batch of product met product specifications.

But validation under a QbD regime aims to establish the design space within which changes may be made to process or product inputs while keeping the product within specifications. As a result, development and manufacturing will have to look together over the entire lifecycle of the process. Development personnel will therefore widen their scope to include issues of manufacturability. Conversely, manufacturing personnel will be looking at development data. Further, risk-based compliance means that manufacturing personnel, who have traditionally focused on issues of efficiency, will have to become decision-makers and risk managers, deciding which parameters to change when necessary or desirable and understanding the associated compliance risk.

From one point of view, it's possible that flexibility for QA could come in the form of fewer deviations and investigations, because the design space will provide clear boundaries to define these. Under QbD, there could be fewer release data to be scrutinized, and acceptance criteria for release specifications would be more scientifically justified. Upstream process data could become more essential to the product quality equation, rather than only quality control (QC) end product testing. Batch records themselves might be less directive and more prescriptive. QA will need to ensure the appropriate data and justifications are documented during processing, rather than simply recording actions taken. All of this may require more process knowledge on the part of QA, but more likely requires only a different outlook on data credibility. For example, during vendor audits, the job will be to assess the risk that materials and services rendered pose to the valid design space. This will require an approach that is more scientifically based than a GMP-checklist style audit, which is currently common in the industry.

From another point of view, it's possible that the FDA's evaluation of GMPs will not accommodate a completely flexible approach to document requirements. Because data produced by development staff must help define the space in which the manufacturing group is free to operate and make changes, quality oversight may in fact increase under QbD. How these issues are resolved between the industry and the agency will be important for conferring the freedom to operate within a design space. The prospect of having such freedom is a major appeal of QbD to the industry in the first place.

Changes in the nature of the QC group's work will be driven by the trend toward real-time quality control embodied in initiatives like process analytical technology (PAT).³ This carries two implications for QC. First, insofar as such control becomes increasingly automated, some QC staff will be freed up to focus on attributes deemed critical to product quality. Second, smart companies will not simply throw new technology at process controls. Instead, armed with greater process understanding, they will be able to determine precisely where the greatest risks and opportunities lie in their operations and to address them strategically. Personnel supporting the manufacturing process therefore will need to become adept at creating, maintaining, and refining PAT and control strategies in line with the goal of continuous improvement embodied in QbD.