Process development diagnosis
The diagnosis of an unexpected outcome or a problem process requires a detailed understanding of the process. What should be happening in the process and what is being observed?
- Are impurities formed?
- During which phase of the process is the impurity being formed – beginning, end or is it continuous?
- Has there been an unexpected change in the performance of a process?
- What is different about the process e.g. different batches of material, different equipment, different scale?
- What was done differently?
- What was different about the molar ratios, order of addition, rate of addition, temperature, pressure, pH, mixing, heating rate, cooling rate, …
- What controls are in place and were they maintained?
- What is known about the process and the specifications for the materials in the process?
- At what point did the process go wrong?
- Are there any in process controls to monitor a typical process and how did this deviate.
The careful selection and use of analytical chemistry is often important to understand and diagnose a problem with a chemical process. The application of the selected tools can provide an understanding of the chemistry and how it is affected by the process. This can then be combined with an understanding of organic chemistry as well as physical organic chemistry and the effects of scale up. The application of a wide skill base aids the development of theories and the creation of tests to prove or disprove the possible theories. Many of these tests can be analytical in nature but it may be necessary to undertake additional experimentation. Experimentation without careful control and analysis may be pointless. A true understanding of the problem will allow the development of a robust solution with suitable controls to ensure the problem cannot reoccur.