Since a lot of process development work has been done on the formulation, I will skip it and focus on API manufacture. API come in two forms, free flowing solid or liquid. Solids are produced mostly through crystallization, spray drying or grinding and drying of the API. These unit operations can be batch or continuous and are well covered in any chemical engineering curriculum.
Majority of API are organic compounds. Every API is a specialty chemical that has a disease curing and life prolonging value. Thus, the manufacturing practices and philosophies applied for the specialty or fine chemicals can and should be applied to the chemicals that cure disease. Since API cures a disease, this means they are toxic and kill bacteria that make humans as well as animals sick.
Most of the times an API manufacturing process are a batch process. Many a times the commercial process is a scale up of how the process was developed in the lab. The purity after each step is analyzed by high-powered analytical instruments and then the next step is carried out. This is a “risk-averse” approach and can be called “quality by analysis.” We are and should be thankful to the approach, as we have had safe drugs. We cannot imagine not checking quality of the drugs. We do not want fiascos similar to the recent animal feed and lead paint on toys. Nevertheless, I call our current pharma methods “belt, suspenders and harness” approach. This approach has big financial implications on a company. Physical structure and equipment investment, raw material, work-in-process and finished goods inventories go up.
We have not applied the best scientific and engineering methods, principles, and practices we taught the world and have practiced in the manufacture of specialty/fine chemicals to the pharmaceutical manufacturing. USFDA in one of its reports suggests the current manufacturing practices are “inefficient and costly.” they are being polite. Regulatory agencies would like the industry to move from “quality by analysis” to “quality by design” but it takes more than words. Regulatory agencies cannot dictate any company how to manufacture their products.
USFDA in its cGMP guidelines has no mention of “continuous processes.” The word “continuous” does not exist in any of their approved guidelines. Pharmaceutical manufacturing chemists and engineers have two challenges: 1) improve their existing processes 2) figure out how to convert their laboratory developments to a continuous process.