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
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.
QA personnel also will need to be involved in defining the design space during validation, working closely with development
staff. QA will change its focus from procedures and investigations to ensuring that the design space isn't breached and that
risks are appropriately identified, assessed, managed, or mitigated. QA will likely ensure that the appropriate personnel
have weighed in on a situation and that there is documented justification for decisions and actions taken. Often, justifications
will come from technical reports, which in most organizations are not as regulated as GMP documents. This may require a new
flexibility on the part of QA, because non-GMP documents may take on a new level of credence in the approval process and beyond.
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.