A process harmonization assessment (PHA) is an efficient tool to thoroughly assess the differences between separate sets of equipment processing a specific molecule. The main components reviewed in a PHA include: process flow, process parameters, equipment capability, and raw materials. A PHA document evaluates the risk to the technical success of a technology transfer by understanding the important process and equipment-related issues early in the process. A PHA document also discusses when differences between sets of equipment may affect critical design parameters for the process such as mixing, heat transfer, column flow rates, and gradient control. Early process development and scale-up may not need every aspect of a PHA document, but node-to-node transfers generally realize great benefit when complete assessments are performed.
Technology transfers early in the development cycle have fewer strictly designed process steps and few if any critical process parameters (CPPs). A simple assessment of the most basic process flows, process parameters, yields, and purities may be enough for a PHA at this development stage. After process development reaches pilot-scale or production-scale, further details in the assessment are critical to reduce risk from unknown variables and ensure both the receiving site and sending site understand the process and the equipment that is being transferred. A PHA document may undergo revisions over the course of a technology transfer as the design progresses, and will continue to be revised as the process changes.
Process Flow Review
The process flow review section of a PHA establishes how the receiving site will fit the process into its major pieces of equipment. This is the earliest portion of the PHA that can be completed. In many cases, a process flow review is completed during due diligence or the initial process fit. Each piece of equipment is selected to enable the major process steps to flow with approximate equipment capacity, product flow through the facility, and process timing. This section may take the form of a process equipment diagram with the process flow shown in a basic process and instrumentation diagram. The process equipment flow creates the inventory of equipment needs at the receiving site and will be the basis of any initial capital project needed to procure major equipment, if necessary.