Ultimately, QbD adoption boils down to a company- and product-based decision about what has the perceived lower risk and cost
profile: to understand the process before licensure and be able to leverage this knowledge to address variability, or to license
a less understood process used to produce the initial batches for validation and then use investigations and corrective actions
to improve it in a limited fashion over time within the bounds of the license (21). The calculation of ROI is highly sensitive
to its assumptions and their projected accuracy. This dependence makes it exceedingly difficult to match QbD investment to
its eventual benefits to assess ROI. Consequently, the pursuit of QbD during product and process development often has been
rationalized based on qualitative improvements and the (often invaluable) benefits of systematic approaches, especially for
delivable tracking, technical reviews, and communication. A key example is an organized, aligned, and justified approach to
risk mitigation, pre-investment, and decision-making. A well-defined QbD strategy, and its implementation prior to incorporation
into a submission, can be used to support and justify QbD costs during the early phases of product/process development.
Continued refinement of quantitative and qualitative ROI analysis is needed, especially based on actual case studies. Most
urgently, several significant benefits remain to be quantified. Specifically, the evolution of QbD consensus among both industry
and regulators is likely to highly influence ROI. Thus, outcomes from the FDA Office of Biotechnology Products pilot program,
as well as industry case studies/mock submissions, are eagerly awaited.
The primary uses of a solid QbD busines case spans all levels of the organization:
1. Manage benefit expectations to justify resource allocations based on product and process risks and timing for pre-investments
on the probability of technical and regulatory success (PTRS)
2. Match the expected QbD benefits to the company's vision of its future QbD state including its risk management strategy
3. Gain solid sponsorship from senior and middle management
4. Sustain enthusiasm through benefit examples for staff at all levels, especially at the bench.
Although a solid business case is important for sustaining strong management support, some argue that solid case study application
examples may outweigh the business case in encouraging initial adoption at the bench level. This tilt in the balance might
be because QbD heavily overlaps with traditional approaches to bioprocess development in some companies. Regardless, it remains
necessary to continue to collect information to improve and refine business case estimation for sustained application.