by Mackenzie Miller
The design or redesign of cleaning systems for biopharmaceutical manufacturing applications is a complex undertaking, but one which can yield significant savings in both the short and long term life of a plant. The following case study examines methods of washing carboys with the goal of reducing the overall cost of cleaning.
Three alternate methods of cleaning carboys were identified: (1) continue the legacy method of handwashing carboys, (2) replace the handwashing step with an automated, GMP-compliant washer and a sterilizer or (3) discontinue the use of carboys and replace them with single-use, disposable bags. The redesign of this cleaning method is a valid candidate for a comparison study because existing alternative technologies may alleviate several apparent disadvantages associated with the original handwashing method such as high labor costs, irreproducible results, and validation difficulties.
Several metrics were used to evaluate and compare these options. The initial capital investment incorporates the expenses associated with switching over to a new method. The weekly expenses dictate the operating costs of using each option and can include the distributed costs of the initial capital investment. The net present value of each option is the cumulative costs of each option taken back to the present value of the dollar. Finally, the breakeven point is the time at which the present value of two or more options are equal, and can designate a timeframe for when one option is preferable to another.
The initial capital investment is a factor only with the option of buying a washer and autoclave to replace handwashing. The capital investment was calculating by obtaining quotes for a Pharmaceutical Grade Washer and a Bio Pharma GMP Steam Sterilizer and attributing 25% of these costs to their replacement of handwashing as the method of cleaning carboys. The remaining 75% of the costs could be attributed toward cleaning other equipment. The initial capital investment costs are summarized in Figure 1. Figure 1: Initial Capital Investment
The weekly expenses were calculated by first obtaining the prices of carboys and disposables using 50L containers as the base for comparison. The cost of utilities for each washing method were estimated using assumptions for the average wash time and amount of water used for handwashing, and assuming the washer and autoclave were loaded to full capacity. The costs of labor, storage space, and disposal were also estimated and included. Finally, the estimations were made for total number of carboys in use, the lifetime of carboys, and turnaround time between uses. These values were projected to calculate the number of single-use bags needed per week. Figure 2 summarizes the weekly costs of each option. The initial capital costs for the washer and autoclave have been distributed over seven years and are included in the weekly expenses for the washer option.
Figure 2: Weekly Expenses with Distributed Initial Costs
The net present values for each option were calculated, accounting for the initial capital costs, the projected the annual expenses, and estimated salvage values. Assuming cost of capital annual rate of 8%, Figure 3 shows the net present value of each option after 10 years.
Figure 3: Net Present Value After 10 Years
Figure 4 is a graph of the cumulative cash flows for the three options over a 10 year period. As shown in this graph, the breakeven point between handwashing and machine washing carboys is at around 2.5 years. The breakeven point between machine washing carboys and single-use disposable bags is after more than 10 years.
Figure 4: Breakeven Analysis
This study clearly shows that valid alternatives to handwashing carboys exist. The economic advantages of these alternatives are evident in comparisons of the weekly expenses, net present value of cumulative costs, and breakeven point. In this case study, switching to disposables was the initial best low-cost option with autoclaving becoming the best low-cost option only after more than 10 years, assuming that the price of disposables and utilities does not change. While this case study identifies the best low-cost alternative for this case, additional factors must be considered when selecting a cleaning method. These factors include the risk associated with validation, development of documentation and training procedures and the environmental benefits, such as using less water and power. A comprehensive comparison of all factors, including cost, will determine the best solution for a biopharmaceutical cleaning method.
Mackenzie Miller is a process engineer for AMEC E & C Services, Biopharmaceutical Division. She obtained her Bachelor of Science in Engineering from Harvey Mudd College. Her project experience includes biopharmaceutical process engineering, design engineering, validation qualification services and start-up / commissioning documentation control. She is a certified Engineer-in-Training and an active member of ISPE.