Issue link: https://www.e-digitaleditions.com/i/1514991
PharmTech.com Regulating Innovation, Quality, and Risk eBook January 2024 Pharmaceutical Technology ® 33 Qualit y Sound infrastructure investment decisions should be supported by a full understanding and accurate quantification of the long-term return on investment (ROI) of a design choice. This is also sometimes referred to as total cost of ownership (TCO). There are many ap- proaches to calculating ROI but they typically are lim- ited to factors relating to immediate capital outlay for hardware, labor, qualification, and other startup costs. These ROIs rarely sufficiently address how a higher ca- pability technology can be a far more beneficial choice than the less capable technological option due to "op- portunity costs." For instance, a higher capability tech- nology will include tighter process control and more conforming units than one of lower capability. Higher capability technologies produce better quality out- puts and higher yields than lower capability processes. These are just two of many direct business benefits of higher capability. Table I describes some additional financial advantages of higher capability technologies. Vital executive oversight role It is well understood that obtaining executive man- agement support is imperative to enable a shift from a lower to higher capability operation. Strong senior lead- ership commitment is essential if needed resources are to be allocated for such improvements. International pharmaceutical industry and regulatory experts have noted the central role of senior management in the ICH Q10 Pharmaceutical Quality System guideline, which emphasizes high capability operations and a culture of continual improvement as core elements of a competent Quality System (14). This culture is driven by ongoing management review of operational state of control, as well as strong systems for change management, process performance and quality monitoring, and CAPA (33). This emphasis on the role of senior management in overseeing pharmaceutical quality is well-placed. Main- tenance of a technological status quo at a company is a near certainty if senior management is not fully aware when the manufacturing infrastructure is substandard or they are unwilling to support needed upgrades. Vigilant senior executive attention to suitability of operational infrastructure and processes is a critical lifecycle responsibility (34). This responsibility is par- ticularly critical because unanticipated operational weaknesses may only be recognized belatedly during the commercial manufacturing lifecycle. Managing risk is a lifecycle endeavor of routinely assuring that a process maintains a validated state, and notably, many failing medicines have been made using equip- ment and processes once considered "validated" at ini- tial product launch (35–39). Impact of inattention to quality There are numerous examples of failures in various in- dustries that illustrate effects of insufficient attention to deficient manufacturing and quality. This "crisis" that Deming warned of (27) has caused severe harm in many well-known instances including the Toyota airbag defects (40,41), Firestone tire defects (42), phar- macy compounding (43,44), dangerous toys (45), train accidents (46), BP oil spills (47), the Boeing 737 Max (48), and coal mining disasters (49–51), among many others. TABLE I. Advantages of higher capability technology (examples). Business Efficiency (cost avoidance) Description Better yield Higher capability technology provides tighter process control and reduced probability of non-conforming units than a lower capability process. This translates to a higher yield. Throughput Same or higher throughput (number of units produced/hour) is a typical feature of contemporary equipment. Earlier detection Averting unexpected downtime High capability equipment provides higher assurance of averting unexpected and lengthy downtimes from equipment failures. Unplanned downtime is also averted via internal calibrations, upstream controls, online real-time measurements, and/or other digitalization features. Further assurance can be added via redundancy (25) in control systems and sensors at weak points to more robustly predict and prevent an issue prior to system failure. While earlier detection and averting unexpected downtimes can be separate technological advantages, we discuss them together here as they often combine for even more synergistic cost efficiencies. Faster turnaround times Faster turnaround times between batches (higher overall productivity and output). Faster Market Launches Developing a high capability operation is essential assure successful technology transfer, first cycle regulatory approval, and timely commercial launch. Inadequate production capability can otherwise lead to very costly delays. Personnel efficiencies Adoption of automation (26) and integrated transfers reduces or eliminates manual activities and human error. Increased quality and reduced supply uncertainty Higher capability technology leads to higher reliability, and satisfied customers. When implemented properly by a company, it produces less failures, returns, recalls, investigations, inventory uncertainties, shortages, customer complaints, market share loss, and other significant costs (27–32).