6.3. Integration of the supply chain into the QbD approach

However, in order to proactively address one of the identified threats of the SWOT the integration of the QbD driven development approach needs to be achieved throughout the whole organisation has to include the complete supply chain as well. Otherwise the risk of eventual failure remains very high.

The supply chain in drug product development does not only include the supplier of the raw materials (drug compound, excipients, packaging materials,..) but also the manufacturers of machines used for manufacturing processes and most importantly contract research organisations and contract manufacturers that fulfil part or all of the development, manufacturing or analytical work outside of the company. The type and extent of these outsourced activities depends on the company’s strategy and can be driven by various objectives, to increase overall capacity, to reduce development costs, or when specific expertise or technology is not available internally.

Once more many levels of interactions with these CROs and CMOs are regulated by CGMP and QA processes whenever they affect clinical supplies or commercial drug products. However when purely developmental activities are outsourced, this has traditionally not been part of the QA oversight.

Therefore, concepts are needed to integrate both, the suppliers and CROs / CMOs into the QbD approach in order to ensure a consistent philosophy and approach throughout the development cycle and life cycle of a drug product.

The most important areas for integration of external supply chain partners are agreements on aligned requirements and processes for quality risk management, knowledge management and change management. Setting up joint risk assessments at the start, updating these whenever new information becomes available, agreeing on steps of escalation and flows of information exchange are essential parts, which need to be aligned and agreed on upfront. Furthermore, the generation and continuation of QbD documents needs to be assured at all times, whether tasks and activities are performed in-house or contracted out.

Therefore, the qualification of suppliers and providers in compliance with these principles and their willingness and capability to commit themselves to these requirements are essential prerequisites and need to be ensured prior to the start of any cooperation and included in the contracts or task specifications.

In this context the internal sourcing and outsourcing departments that initiate and define contracts with suppliers and external providers also need to be integrated into the QbD concept.

Finally it is absolutely essential to align intensively with production early during development to ensure that the developed processes will meet the capability requirements of the manufacturing environment. Successful transfer of development processes into routine manufacturing and production allows production to fully benefit from continual improvement potentials, but this can only be achieved via such close alignment between development and production. This is ideally supported by continued process monitoring with the same configuration and the same measurement tools as employed during development.

The needs for integration were identified in the SWOT analysis and therefore incorporated into the roll out plan. Production can most straight forwardly be integrated by aligning the initiatives of operational excellence at the production sites with development’s QbD program as part of the milestone plan for the roll out of QbD. Internal and external supply chain activities are addressed in a parallel program, initiated to define requirements and processes for qualification of providers for the development and manufacturing of investigational drug products.