|dc.description.abstract||The initiation of this project was based on the need to produce investigational drug products for trial purposes. Such products are to be produced by a licensed GMP compliant facility. The design of the pilot facility at the NWU (Potchefstroom campus) originated from the fact that this institution had the available human resources, equipment and premises.
Feasibility investigations that had positive outcomes were conducted, with the exception of the challenge posed by the limited size of the premises and the apparent limited budget in the early stages of the project. The feasibility findings reflected that the allocated site for this project was not suitable for Pheroid production. The site was too small to contain the process requirements without increased risk to worker safety, worker comfort and materials protection. An outcome of this project was to contain the processing requirements in a defined processing vessel. The vessel thus becomes an integral and critical component of the Pheroid production process and, therefore, to the facility design.
Several investigations into process and product requirements, critical parameters, and user and regulatory requirements were done, in order to establish a conceptual model, based on the assumption that a specialised pressure vessel would be produced. As this facility design model was based purely on these requirements and on very little practical engineering knowledge, the first concept model produced was called the theoretical model (model 1).
This first theoretical design was essentially based on the process and regulatory requirements and the low budget allocated for this project. This first design required retaining, where possible, the utilities of the allocated facility in their current locations, namely the weighing area, the sink and electrical utilities, but this was not suitable in terms of process and material flow. The intent to minimise costs therefore resulted in the inclusion of an isolator unit to achieve the desired level of protection. Upon evaluation of the theoretical design by the first engineering consultant, the commissioning costs quoted to establish the isolator unit exceeded the budget requirements. The achievement of the pressure differentials to maintain the desired level of protection with the isolator area was also not practically feasible.
The cost implications of producing this first model were such that it would be very close to the cost of turning the entire facility into a fully operational cleanroom. This
scenario was vastly altered when the project received further funding that could accommodate the cost of an air handling unit (AHU), thereby achieving a higher level of protection for the entire facility. This change thus enabled the suitable location of component areas as required by material and operational flow. The impact of implementing the first theoretical design would consequently have resulted in increased lifecycle costs for the facility, as this shortcoming in the design would have necessitated correction. These alterations would have implied further costs over the facility's lifecycle, as opposed to the higher initial cost of establishment and lower maintenance cost.
Model 2 was thus designed as a cleanroom with a simple AHU so as to achieve the desired level of product protection and user requirements. It was then evaluated and it showed that the layout and capacity of the air handling system within the facilitiy was inadequate for achieving the desired level of product and material protection. A fully-fledged heating, ventilation and air conditioning (HVAC) system was then considered, in order to meet the required demands, giving rise to model 3 evolving from this set of circumstances.
Evaluation of model 3 revealed shortcomings regarding the safety requirements and the efficacy of the HVAC system. This resulted in the design of model 4 which upon evaluation met the engineering; health and safety; user's; product's; process; and material flow requirements. The model was then divided into component design requirements. Diagrammatic layouts of each of these components were established, to collectively contribute to the generation of the final architectural draft which would be used as the blueprint for the facility.||