Achieving Process Intensification by Scheduling and Debottlenecking Biotech Processes - An approach to reduce batch time, increase productivity, and decrease costs. - BioPharm International


Achieving Process Intensification by Scheduling and Debottlenecking Biotech Processes
An approach to reduce batch time, increase productivity, and decrease costs.

BioPharm International
Volume 24, Issue 2, pp. 44-53


This section proposes a simple approach that could be used for process scheduling and optimization. The approach is manual and requires common platforms, such as Microsoft Excel. As mentioned earlier, however, commercially available software also can perform this task. The key inputs for this analysis are the process flow diagram; information on time, labor, buffer, and media (if any) required for each step, and equipment specifications (for existing process).

Step 1 focuses on evaluating process economics. First, we calculate the net fix, expenditure for each step for a single batch, including recurring cost and non-recurring cost, (eq. 1),

in which NE(i) is net expenditure for each step per batch; t(i) is batch time (h), W is average labor wage (per day); N l is number of laborers required for operation; T is shift time (h); ReC(i) is other resource costs (media, WFI, etc.); C(i) is equipment cost; N b is number of batches per year; and T e (i) is equipment life (in years).

Next, we calculate the production profit per batch (PP) (eq. 2),

in which SP is the selling price of the product.

Assuming that the amount of raw material used is proportional to the production capacity, a new parameter E can be defined for cost analysis (eq. 3),

in which, E is constant and does not depend on the number of batches produced per year (N b ).

The cost index (n) can then be defined in (eq. 4),

in which, N b (i) is the changed number of batches per year because of the addition of new equipment (i = 2,3,4...); and N b (1) is the number of batches with each single piece of equipment.

The cost index (n) is greater than 1 if the change is profitable. Therefore, scheduling should be continued while n is increasing. This strategy ensures that any change made improves overall profitability.4

Step 2 involves creating an equipment- occupancy (EO) chart for the existing equipment. The chart can be in the form of a Microsoft Excel worksheet, that lists equipment on the Y-axis and time scale on the X-axis. Once the chart has been created for the first batch, the EO chart for the second batch is created by shifting data on the horizontal time scale toward the right until the bars do not overlap. This step can be repeated for subsequent batches. Commercial software also can generate similar EO charts.

Step 3 entails batch-time analysis. Cycle time is the current bottleneck in the production scheme, but it can be reduced by adding equipment, which will increase the number of batches per year. The EO chart can be used for this purpose, and separate charts can be created for the upstream and downstream processes if they are performed independently. This activity is continued until the cost index increases, but attention should be paid to ensure that cycle time remains the same after the final scheduling so that storage capacity is not exceeded. If this step is performed for a multiproduct biotech facility, debottlenecking is first performed for the different unit operations for one process and then for the different processes that are run in the same facility. A given process segment (e.g., harvest) must be complete for one process before the equipment is used in the second process. For a typical multiproduct facility, this step can be tedious because of the large amount of equipment, coupled with various process constraints.

Step 4 involves optimizing tanks and other equipment required for buffer and media preparation and storage. The EO charts can be used to calculate the volume and type of buffer and media required during each shift (8 h), and a preparation scheme is then prepared considering the stability of the buffer/media. The number of times a buffer/media preparation tank can be reused in a shift is calculated by dividing the shift time by the average time required for preparation of any buffer. The number of tanks needed can be minimized by maximizing the reuse of tanks.

This approach is illustrated in the two case studies presented below. Both of these case studies are based on real biotech therapeutic manufacturing facilities.

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