Figure 1 depicts a product build map for the single-use assembly that can be used as a guideline during the risk-assessment phase.
This map provides a framework to assist in the risk analysis of the supplier's product. Each leg or arm provides checkpoints
in the manufacture process to evaluate CPPs. By following a risk-assessment process, safeguards can be established and implemented
at various steps to mitigate risk. Appropriate risk-mitigation tools can be used throughout the assessment activity, for example
failure modes effects analysis (FMEA) spreadsheets or fault tree analysis (FTA) flowcharts (refer to ICH Q9 Quality Risk Management available tools) as a way of identifying crucial issues with the manufacturing process of a single-use product.
Figure 1: Single-use systems, process build map.
As with many components used in the manufacture of therapeutics, a lifecycle management approach may also be adopted for single-use
systems. The lifecycle management approach delineated in the ICH Q10 guideline discusses the application of various quality
tools to the development, technology transfer, manufacturing, and discontinuation phases of a products lifecycle. This process
is illustrated graphically in Figure 2.
Figure 2: Pharmaceutical lifecycle management.
The lifecycle management process is an iterative process with programs designed to capture changes to the product through
both management review of performance data and through the quality system in which product quality is maintained through a
corrective and preventive action program (CAPA). Manufacturers and suppliers should take into account the establishment of
testing parameters, product transfer techniques, production parameters, and controls for GMP of sub assemblies. QMS/CAPA control
schemes should be in place to review and control process. Storage and shelf-life management systems should be set up. A discontinuation
program and obsolescence programming (supplying until an effective date) should also be considered. When vetting suppliers
and manufacturers, these points will aid in the selection of the right source for the procurement of such critical-to-quality
It is imperative that the framework of manufacturing control parameters be established early in the contract development process.
Sourcing should be done from approved suppliers. Quality change-management systems should be established with the supplier
so that any changes arising from supplier process improvements are documented and approved early in the change process. Setting
these controls in place during contract establishment will facilitate a smooth approach to manage improvements to the supply
process. Mitigating risk is to be viewed as the primary driver.
Once a supplier has been established as a qualified supplier, defined by the supply change-management process, routine scheduled
inspections of the supplier and subsuppliers will be required. Performance of these inspections and review of control parameters
that have been established in the master contracts are important to reduce likelihood of out-of-specification components being