The primary reason for the pharmaceutical industry's hesitancy to adopt rapid micobiological methods (RMMs) for environmental monitoring is a lack of understanding of how to assess the cost of implementing such methods. This article explains how to apply a financial cost model to RMMs and presents a case study of three manufacturing facilities of different sizes. For the three facilities evaluated, the year 1 return on investment for implementing an RMM ranged from 183 to 365%, and the payback period ranged from 3.3 to 6.6 months.
The FDA's Process Analytical Technology (PAT) guidance document describes a regulatory framework that encourages the development and implementation of innovative approaches in pharmaceutical development, manufacturing, and quality assurance.1 One of the key opportunities the document offers is the introduction of new analytical technologies intended to measure, control, or predict product quality and performance. The goal is to design and develop well-understood manufacturing processes and facilitate continuous improvement and operational excellence. Many in the industry regard in-line and on-line physical and chemical technologies as the primary enablers in the PAT toolbox. However, alternative microbiology platforms, such as rapid microbiological methods (RMMs), are now being implemented under the PAT umbrella for ensuring that a state of microbial control is maintained during manufacturing. Although a number of firms have already validated RMMs, it is unfortunate that the majority of the pharmaceutical industry continues to show apprehension about embracing RMMs. Concerns regarding the availability of validation strategies and regulatory acceptance have, for the most part, been satisfied through numerous guidance documents2–4 as well as by presentations and papers provided by regulatory authorities.5–7 It is this author's view that the primary reason for the industry's hesitancy to adopt RMMs is a lack of understanding of how to apply financial cost models to economically justify the implementation of these alternative technology platforms. This view is supported by the understanding that manufacturing site heads and production managers want to be convinced that the return on investment (ROI) is sufficient to substantiate the time and expense involved in qualifying and installing RMMs in their facilities.
There are obvious costs involved with the purchase, qualification, and implementation of RMMs. Depending on the capital expense and the process required to adequately validate a system for its intended use, the costs associated with implementing an RMM can be significant. However, it is important to fully understand all of the financial components that should go into an economic analysis before a decision is made about whether to proceed with a formal qualification program. These components may include the costs associated with the existing method, the costs associated with the initial capital investment of the new method, and the long-term financial benefits (cost savings and avoidances) that the RMM may provide. Dollar amounts for each of these components can then be used to develop a comprehensive economic analysis and business case for introducing the new method.
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The three key steps for considering the implementation of an RMM are as follows:
1. Review existing conventional methods and recognize potential technology, quality, and business opportunities for implementing an RMM.
2. Understand the technical and business benefits of RMMs.
3. Develop a business case for RMMs.
Below, we explain these steps, and provide a case study to illustrate them.
REVIEW CONVENTIONAL METHODS AND RECOGNIZE OPPORTUNITIES FOR IMPLEMENTING AN RMM
Manual sampling and resource-intensive operating procedures are responsible for much of the cost associated with conventional, growth-based microbiology methods. In addition, the time to result when turbidity is visually detected (in liquid media) or colony-forming units are enumerated (on agar plates) can be quite long. Furthermore, microorganisms that are stressed, damaged, or in a viable but nonculturable (VBNC) state may or may not replicate when cultured on artificial media. In the event of a positive result or an out-of-specification finding, which could occur anywhere from a few days to more than two weeks after the original sample was analyzed, the opportunity to respond to the excursion in a timely manner has been lost. In addition, the effect of an environmental monitoring (EM) excursion on the manufacturing process could be significant, including holding product, rejecting a batch, or shutting down a manufacturing line. In contrast, obtaining these results faster, or even in real time, through RMM, would allow corrective action to be taken quickly, thus reducing the number of lot rejections and plant shutdown time for EM investigations. For these reasons, companies should explore the use of RMMs that may decrease the overall costs associated with conducting microbiology testing while at the same time continuously improving the manufacturing process, finished product quality, and operational efficiency.