Achieving those many benefits, however, will require adopting new ways of working and a new outlook on good manufacturing practices (GMPs). What will QbD mean in that regard? The answer lies in the convergence of science and compliance at the heart of QbD: (1) robust processes designed to provide statistically defined performance characteristics that ultimately result in products with a defined target product profile, and (2) good biopharmaceutical quality, defined as an acceptably low risk of failing to achieve the target profile. In other words, QbD combines increased scientific understanding of products and processes with the risk-based compliance that such understanding makes possible.This convergence of science and compliance will profoundly affect all areas of GMPs, including the nearly 20 such areas covered in the International Conference on Harmonization (ICH) Q7 guideline.1 Each GMP could, of course, be the subject of extended discussion in light of QbD, but more generally, the convergence of science and compliance will mean:
Under QbD, GMPs will be reconceived as a framework, rather than as the driver, for the performance of risk-based, flexible processes. In other words, if biopharmaceutical companies are to maximize the benefits of QbD, the technical and compliance revolution it embodies will need to be accompanied by a cultural and organizational revolution.
COORDINATION ACROSS DEPARTMENTS
Most companies have spent years carefully establishing and elaborating the steps involved in the manufacturing of biopharmaceutical products—from the initial cell culture vial through scale-up, bioreactor production, downstream processing, formulation, filling, and packaging. Not surprisingly, this approach has encouraged the development of functional silos, each narrowly focused on its area of expertise, inhibiting the diffusion and integration of knowledge throughout the organization.
This model of drug production, with little crossfunctional involvement after each hand-off to another function, and with quality ensured through analytical testing near the end of the process, has served biopharmaceutical companies reasonably well for decades. But with tighter regulation and cost pressures that now reach into development and manufacturing, companies are seeking more efficiency in manufacturing processes by improving process understanding and control.
QbD, with its aim of achieving a scientific understanding of manufacturing processes as early in the development process as possible, and of enabling continuous improvement in manufacturing, requires a much more integrated and holistic approach by staff in all functional areas. For example, in elucidating and, in particular, documenting the process design space (defined in ICH Q82), development groups may need to operate with an increased attention to GMP guidelines because the data they develop by using design of experiments (DOE) to define the design space will be used to support manufacturing decisions to the FDA. Analytical and bioanalytical support functions will share in the responsibilities for this key element of process design and control.
In essence, succeeding with QbD requires creating a continuous feedback loop between development and manufacturing, with upstream, downstream, and analytical personnel increasingly looking as far down the production process as possible, and manufacturing personnel reaching back into earlier stages of development, all tied tightly together by improved communication and documentation facilitated through IT groups.