of the Final (Solid) Product
Ensuring Regulatory Compliance of
Sales Products Worth $20,000,000
Typical cooling crystallization from 95°C to 10°C of large prediction process at an API company during the final step in the processing of the API material
Rpm was lowered from 86 to 50 when the reactor content reached 42°C.
The physical properties of the final product (bulk density and tap density) were higher and out of spec. A total of 94 batches were produced in the course of the year, and 38 of them were out of specification, representing approximately 40% of the entire yearly production (without including some limited batch results).
Stabilize the bulk density and tap density of the final product at the production stage.
The Traditional Approach
Trial and error of different operation parameters was used in the production scale. A solution was sought in the solid treatment of the process, at the milling and screening stages.
The VisiMix Analysis
VisiMix was used to conduct experiments in the laboratory in order to understand the effects of the hydrodynamics of the physical quality of the product.
The VisiMix Solution
Lowering agitator velocity during the entire crystallization stage to 50 rpm.
Significant decrease of out-of-spec material, similar to the production in previous steps. Rate of failure was lowered from 40% to 20%.
Calculation of the Savings
Savings were realized at two levels:
1. Lost batches: $200/kg * 50 rejected batches * 85 kg/batch = $850,000
2. Potential losses due to regulatory issues: before using VisiMix, the process produced inconsistent results, with severe regulatory consequences. Using VisiMix enabled us to stabilize the results of the process and avoid regulatory problems and questions. (Sales of these products amount to more than $20,000,000.)
Process: Cooling crystallization at final step in the API industry
Task: Stabilizing the bulk density and tap density of the final product at the production stage
– 94 batches
– 38 out of spec
– ~40% (not including limited results batches)
Laboratory experiment plan and results based on VisiMix recommendations
VisiMix helped determine the repeatability of the batches during production by applying QbD, using VisiMix calculations as the basis for the experimental set of runs.
1.Control bulk density and tap density in the production stage of the final API material
2.Improve the repeatability of the batches in the production based on Quality By Design (QbD)