6.5.3. Streamlining of project times facilitated by QbD

As already indicated in the pre-formulation example above, QbD driven development may actually succeed in reducing timelines, despite the claims from critics, that QbD prolongs development timelines. By applying a systematic and risk based decision matrix only those activities will be pursued at each stage which are really critical to the defined target profile and for the required product performance, rather than performing a list of routine activities for each phase of development. Therefore, net timelines for development of pre-clinical or FIH formulations can be reduced despite additional scientific investigations or DOE based formulation and process development, which may be required as a result of the risk assessment and approved mitigation strategy in a specific project.

To achieve this, the minimum activities as required for a QbD approach can be defined and decision tree structures established for activities related to the most commonly experienced risks. Thus a modular, systematic workflow employing the QbD elements and experimental building blocks can be set up for each project using the development handbook and a systematic review of quality related processes and their interfaces, as a baseline.

While the type and extent of investigations needed at each development phase will be project specific and dependant on the identified CQAs and risks potentially impacting these, the building blocks can be combined to a process flow and defined by the pre-requisites, deliverables and documents needed for each of these. Then average standard timelines needed for each of the building blocks can be defined and combined in the process flow, resulting in average times for CMC activities for a specific task or development phase.

Removing unneeded tasks and activities and improving interface alignment with all stakeholders then results in optimised timelines. Setting stretched but realistic objectives as to future time requirements for each phase is thus possible, cutting some of the traditional time frames by half, without an increase in the resources needed to perform these phased activities.

As a result of this strategic program development times for FIH formulation can be cut down to 6 months for all oral dosage forms, including 3 months of stability data to support decision for FIH formulation. Manufacturing of bulk materials and packaging of clinical trial supplies for a FIH study can also be cut down to 6 weeks from availability of released raw materials to release by the Qualified Person and distribution of the clinical trial medication.

These QbD aligned timelines can be achieved for both, projects run internally and outsourced projects for the manufacturing of clinical trial medication. The latter being the bigger challenge due to the requirement to align and optimise all process steps and timelines within the complete supply chain. However, when integrating the external contract organisations and the complete supply chain into the QbD approach as described in Chapter 6.3 this can bet managed successfully too.

Thus QbD results not solely in improved quality but in an overall improvement of development timelines and the quality of projects, ultimately lowering R&D costs for new drug products. If not for the clinical studies, but definitely for all CMC related R&D activities QbD can lower the risk of project failure and increase R&D profitability delivering more successful projects for the invested money.