Process development cycle

Process scale-up, which deals with transferring the laboratory process to a semicommercial or commercial scale facility while achieving the same cost, quality, and physicochemical characteristics as those achieved in the lab. 

Despite the issues discussed above, generic companies have been successful in developing products within very tight time lines. How has this been possible It is our experience that several factors contribute to the success, or failure, of process development work (1) cross-functional skills and teamwork, (2) system-driven process development work, (3) planning and monitoring, and (4) nimbleness in decision making. 

Typically, process development for an API takes about 9 to 12 months from route identification to commercial-level scale-up. The process development cycle is shown in Fig. 23.1. In the figure, the solid lines represent the normal flow of a process from laboratory scale (10 to 1(X) g) to kilo-lab scale (500 g to 2 kg) to pilot-plant scale (5 to 50 kg) to full 

Process development activities are planned to run parallel to each other to the greatest extent possible. Standard operating procedures, guidelines, and protocols need to be in place for aU key activities, from lab scale until commercialization. The activities are micromanaged through project management tools. In this section we discuss various key factors associated with process development and their impact on the product quality and yield. Instead of discussing the complete synthetic sequence of any particular product, we illustrate typical problems that could arise in any development process with real-life case studies from our experience. 

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Fig. 7.2 illustrates for the pharmaceutical industry 1) the major milestones or events in the process development cycle and (2) a typical sequence of events. The process... 

Another important aspect of detection in the process development cycle is the identification of a wavelength(s) and a cell path length that allows one to monitor the process response. The best way to address this issue is experimentally. The final testing and determination of the cell path length that gives an on-scale response will likely have to be done on the production floor. 

The primary considerations which need to be addressed during or after the process development cycle with respect to environmental issues are (1) disposal of spent packing, (2) solvent disposal, (3) solvent recovery. (4) obtaining the air permits for the solvent systems in use, (5) systems in place to meet OSHA and EPA guidelines, and (6) the DOT classification. Environment guidelines and regulations are not within the scope of this chapter. 

Polymerization and nitration are two particular examples, which are well understood but regularly misjudged at considerable cost, even by experienced companies. PI equipments (e.g., S D R) potentially offer a scale-independent way of eliminating such hazards. They offer the possibility of faster process development cycles, tiny inventories at risk and negligible risk of safety or quality pit-falls as production is scaled-up. 

It is also useful to depict the bulk drug process development cycle on a Cartesian coordinate plane (Fig. 6). The... 

From the above definitions, a discussion of the specifics of each stage is now possible, also based on the depiction of the bulk drug process development cycle on the know-how vs. applied effort plane introduced in Fig. 6. During these stage-specific discussions, the three bulk development tasks will serve as the basis and along the lines of Fig. 5. 

This text covers those three activities of development, manufacturing, and regulation in its broadest sense. This will include discussions on the process development cycle, introduction of the process into factory design engineering, regulatory matters that include the regulatory approval pro-... 

The Petri Nets are a powerfirl method to approach various kinds of discrete event systems. They allow expressing efficiently a variety of phenomena such as sequences, parallelism, synchronized start and stop, etc. They get the advantage to be able to be used both for the modelling of a static structure and the dynamic behaviour. They allow in this way to examine not only the system architecture but also its temporal evolution andreactions to stimuli. This makes them very suitable for the dependability, safety and performance evaluation. CPN can be employed throughout the complete process development cycle one can thus preserve the same formalism to imderstand the architecture and the behaviour of the process (as well as the lunctional analysis). The driver model and various test scenarios can be also implemented in this formalism. 

There are already many examples of advances ofPSE embedding sustainabihty aspects as part of the process development cycle. Continuous microreactors from Coming utilized for fine chemicals and pharmaceuticals [97], continuous formulation processes, process intensification demonstrated in several processes [98], and life cycle assessment evaluations integrated into process development [99], to mention a few. However, a more widespread uptake is needed, so they are used routinely. 

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