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32 Pharmaceutical Technology ® Regulating Innovation, Quality, and Risk eBook January 2024 PharmTech.com Qualit y Broad implementation of highly capable manufac- turing has been shown to be transformative in ele- vating the level of quality in various industries. For pharmaceuticals, the fundamental goal of maintain- ing an ongoing state of control to consistently deliver safe and effective medicines is a major focus of the International Council for Harmonisation's (ICH's) Q10 guidance, Pharmaceutical Quality Systems (14), which states that "the goal of pharmaceutical development activities is to design a product and its manufac- turing process to consistently deliver the intended performance and meet the needs of patients and customers. The goals of manufacturing activities include achieving product realization, establishing and maintaining a continued state of control, and facilitating continual improvement." A great part of ICH Q10 was based in good manu- facturing practice (GMP) requirements for rigorous operational design and process validation. For ex- ample, regarding the latter, FDA clearly articulate the requirement for robust medicines production as follows: "manufacturers must maintain the process in a state of control over the life of the process, even as materials, equipment, production environment, per- sonnel, and manufacturing procedures change" (15). Societal benefits of manufacturing improvements The societal value of manufacturing improvements is well established in literature, from both economic and public welfare perspectives (16). Benefits can in- clude enhanced economic competitiveness, budget- ary cost efficiencies, public health protection, better quality of life, and increased social equality. In some cases, industries have seen the value in driving positive societal changes. For example, large capita l invest ments were made in rec ycling pro- grams before they were required by law (17). In this case, executives saw the long-term shared value to the company (e.g., there are supply chain efficiencies attendant to recycling materials rather than dispos- ing of them in landfills) and society (18). Notably, many in t he pharmaceutica l industr y have similarly seen value in making advances in green chemistry and sustainable technologies (19). When there is a compelling business case (20,21), a company is far more likely to invest in improve- ments that are also mutually beneficial to society. T he potent i a l soc iet a l m ac roeconom ic benef it s of qualit y improvements are summarized well in an American Societ y for Qualit y (ASQ) paper (22), which notes five ways in which "improvements in product quality can be a catalyst in the betterment of national economies and the lives of people: Com- petitive advantage in exporting, national trade defi- cits, economic growth, standardization, productiv- ity and customer satisfaction." Business case for investing in manufacturing reliability Infrastructure investments generally require a large expenditure, and thus a corresponding major com- mitment from top company executives who allocate budget. In addition, high-performing equipment and facilities may be initially more costly than their lower performing counterparts. The business case for a large capital investment would be fundamentally lacking in balance and sufficiency if it only considers short-term costs and benefits. Thus, when the long-term view of financial benefits is lacking, and a myopic view toward rapid recovery of initial investment prevails, this skewed understanding deprives the organization of knowledge regarding the long-term cost savings and other benefits of higher manufacturing capability. While there is some awareness in the pharmaceutical industry of the cause-and-effect relationship between higher quality assurance and financial benefit, a well- rounded model that quantifies lifecycle ownership ben- efits and costs is critical to calculating the true value of a proposed investment and selecting between options. Implementing such an analysis may be a challenge in some organizations where the leadership only seeks short-term financial benefit, rather than focusing on the long-term stability of the organization. Unfortu- nately, when long-term corporate health is sacrificed in favor of short-term earnings, the poor stewardship that led to such decisions is often only revealed belatedly (23). To ensure an accurate long-term forecast, a business case model should account for the downstream effects of unstable production operations on the organization's ability to meet its strategic objectives. An effective business case may also be aided by knowledge of where the company stands in its tech- nological maturity in comparison to competitors. Yet there are very few efforts in the pharmaceutical indus- try to establish a benchmark that measures whether a company is using technologies and reaching quality outcomes that are equal to modern attainable stan- dards. In contrast, the computer industry consistently uses technological benchmarks to compare manufac- turing system capabilities and quality performance (24). In many cases, proven technological solutions are already available that can resolve longstanding drug manufacturing reliability issues that can pose hazards to consumers. Yet in some cases, companies still fail to upgrade their facility and equipment design, and in- stead allow the status quo to persist. But why? The answer is complex and decisions are not always strictly guided by financial considerations. Nonetheless, an understanding of the factors, and more standardized approaches to analyze if there is a busi- ness case for upgrading production capabilities, may be pivotal to more consistently drive effective resolutions to major drug manufacturing problems.