OR WAIT null SECS
Creating closed processes and reducing room air classification in a biopharmaceutical facility can reduce operational costs.
The operating expenses of a biopharmaceutical manufacturing facility are significant and contribute directly to the cost-of-goods sold, thus management is always looking for ways to reduce operating expenses. Recent efforts have focused on the savings that can be realized from closed processing, especially single-use technologies, when combined with a reduction in room air classification. This article presents a case study for an existing, cell-based manufacturing process where isolators were added and room spaces were downgraded from Grade A or B to Grade C, as defined by the European Union’s Good Manufacturing Practice Guidelines (1).
This case study assesses the compliance risks and cost benefit (i.e., return on investment) that resulted from changing the classification of a suite of rooms containing a biological process. Except for two specific, open procedures, the processes involved were all closed, aseptic operations. The facility was a 3600-ft2 processing suite composed of two, 21-ft x 16-ft Grade A processing rooms with full laminar-flow ceilings. The existing open processes within the two Grade A rooms had to be executed under aseptic, laminar air environments. These rooms were surrounded and supported by a series of Grade B spaces.
The renovation created a single Grade B suite that supports two Grade A isolators for the open processes. This renovation allowed downgrading of the rest of the 3600-ft2 suite to Grade C. Table I summarizes the square footage change and shows that more than 80% of the space was able to be downgraded.
|Existing suite (ft||Renovated suite (ft|
To make these changes, modifications to the physical plant were required. Four existing rooms were reconfigured to create a single, 330-ft2 Grade B room to house the two isolators and their processes. Separate personnel entry and exit airlocks as well as a separate material airlock were built to provide access to the Grade B room. The two existing Grade A laminar flow rooms were maintained as they were, but their air change rates were reduced and requalified as Grade B space; this strategy was chosen to save construction costs and to allow the potential for the rooms to return to a Grade A air classification if required by a yet unidentified future process. All the remaining spaces were downgraded to Grade C without further modifications.
The construction cost for this work was quantified by an experienced construction manager at $150,000. The cost of the isolators were provided by the owner at $700,000 each.
Based on the new room configuration, the reduced air classifications, and the revised procedures supporting the changes, the team analyzed the annual savings that could be expected, as follows:
Table II shows that the total sum of the savings is just over $1 million a year. The cost of environmental monitoring, especially for gowns, is the single largest savings by nearly a factor of four.
|Environmental monitoring of area and personnel||$530,000|
|Total annual savings||$1,013,000|
As discussed, there are investment costs before any operational cost reductions can be realized. The capital cost to modify the facility and purchase new equipment must be taken into account. Table III shows the cost needed to create the new isolator suite, rebalance the new air classifications, and purchase two new isolators.
|Construction and rebalancing||$150,000|
This study did not identify costs required for requalification of the new room classifications. Comparing Tables II and III, however, the hard costs of equipment and construction, when considered by themselves, return their value in 18 months. In addition, there are operational savings in terms of time, which result in greater efficiency and have the potential to be converted to more production capacity and the corresponding additional revenue.
The company that undertook this study recognized that substantial costs were unnecessarily being spent on maintaining Grade A and Grade B spaces. By evaluating the process, doing a risk assessment, and reconfiguring the space appropriately (including right sizing of critical spaces), the majority of the cell-processing area could be successfully downgraded to Grade C. The key was defining the area where open processes occurred and moving these into closed-process isolators.
The savings potential for other facilities begins to become apparent when you consider that in this example, a 3600-ft2 facility returned $1 million in cost avoidance annually. For a larger facility where the process allows similar improvements, it is reasonable to expect even greater returns. Unless a facility is being built new, an upfront capital investment will be needed to make the necessary modifications, but the return on investment could still be worth it. In addition, there is a potential advantage gained in operational time. The 3200 hours saved here is equal to 1.5 FTE (full-time equivalent) over the course of a year. These hours are made available for other, more productive activities and can help drive the facility towards greater efficiency and higher productivity. This case study demonstrates the multiple benefits of striving towards closed processing. By understanding the process and appropriately providing protection where needed, substantial operational savings are possible.
1. EC, EudraLex Volume 4: Good Manufacturing Practice Guidelines, “Annex 1, Manufacture of Sterile Medicinal Products” (Brussels, 2008).
About the Author
Eric Bohn is partner at Jacobs Wyper Architects, 1232 Chancellor St., Philadelphia, PA 19107, tel: 215.985.0400.
Article DetailsPharmaceutical Technology
Vol. 39, No. 9
Citation: When referring to this article, please cite it as E. Bohn, “Generating Savings from Room Declassification,” Pharmaceutical Technology 39 (9) 2015.