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PharmTech.com Quality and Regulatory Sourcebook March eBook 2023 Pharmaceutical Technology ® 35 K nowledge ManageMent char t, is that each of these par ts is managed sepa- rately, at the risk of their interfaces becoming "sins of omission." Such fragmentation is justified at the detailed technical level, given the complexity and multiplicity of the systems involved. What is at issue, however, is the mechanism whereby these depart- ments and their related systems communicate. From a syntax perspective, each of the above parts is equivalent to a word, and their integration into a quality quartet that of a sentence. By comparison, attempting to communicate meaningfully at the word level leads to incoherence and misunderstanding, both personally and technically. What this monograph is recommending therefore, is an exercise in biopharma sentence making, and stringing such sentences together to build procresses. Note that each department can and should retain ownership of its specialist word vocabulary, in sup- port of the fine detail for which it is responsible, but with sentences now elevated to a shared interdis- ciplinar y level of ownership. To demonstrate that a ll of this is relevant, "[CQA:CPP:CA:CDE]" trans- lates to "t his qua lit y quar tet relates to t his CQA, which requires this CPP, this CA, and this CDE, to ensure its validit y," and vice versa. Using the ear- lier CQA vs CPP monitoring example by way of il- lustration, this has the following user requirement specification (URS) implication, which readers may wish to self-assess: "your monitoring system and my monitoring system must be interconnected." Discontinuity Evolutionary biologist Richard Dawkins has bemoaned what he calls the "tyranny of the discontinuous mind," and its pervasiveness across sectors and disciplines (14); in engineering, this is reflected in the conversion from analog to digital technology, both domestically and commercially (i.e., always specif ying the most modern available option). Our senses and cognitive systems are analog (i.e., continuous) but our measure- ments are digital, which is counterintuitive. Where such devices are utilized as part of a quality quartet, it is important to specify their polling frequency as well as their accuracy, and to ensure that what is on display is in fact the actual value, and not the setpoint. The superiority of today's metrology is not in ques- tion, but there is a lesson to be learned by human machine interface designers and end-users within quality quartets. One counterexample to this is the car speedometer, which still relies on an analog rep- resentation of speed (and acceleration), in spite of the availability of a digital equivalent. While speed val- ues are based on digital increments (e.g., a 200 step/ rev stepper motor = 1.8° per step on a round dial; the dial being round because wheels are round) the over- all display is analog, in line with long-standing driver (and passenger) preference. Readers may wish to posi- tion the speedometer, and specify its three associates, in this "happy motoring" quartet. By the same token, there is an occupational hazard for risk assessors here, particularly when agonising over, and sometimes hiding behind, relative positions on an arbitrary high medium low scale. A compounding fac- tor is the fact that we are dealing primarily with batch manufacturing processes. These are inherently discon- tinuous, and this has affected our industry's overall mindset and view of the world. A final example of this mindset is the industry's current interpretation of C&Q stage gates as being "normally closed," and obstacles to progress. The new paradigm turns this on its head, and uses validity statuses to enable sequential review and approval of quality quartet parts. On this view, quality quartets and their parts can be viewed as members of a sprint team in a relay race. Definition—quality quartet A quality quartet is a knowledge management out- put, also known as Justified Tr ue Belief (15), that provides a continuous and testable expression of the understanding that a firm possesses about the relationship between CQAs and CPPs and their associ- ated CAs and CDEs. Figuratively speaking, quality quar- tets have a valency of four. Recommendations The recommendations included in the preceding sections are repeated here for reference: • Assig n u n ique I Ds a nd t i me st a mps to t he quality quartets. • Manage these objects as fundamental super-assets. • Create a one-page x fou r-box dat a sheet for each quartet. • Create a precision pyramid for each quartet. • Create an evidence pyramid for each quartet. • Qua l i f y qua r tet pa r t s v ia IQ (CDE), OQ (CA), CPP(PQ), CQA(PV). • Pre-qualify the quartets in toto in the course of DQ. • Create a four-part quartet "assembler" based on prior knowledge. • Use the totality of quartets as your control strategy deliverable. • Define quality as the flipside of risk, to be assessed simultaneously. • Don't multiply risk assessments beyond necessity. • Don't be dismissive of analog data. Conclusion All of the ingredients required for C&Q and QRM opti- mization are already available within the industry. This monograph is an engineer's positive contribution to pull- ing these disparate strands together, via the introduc- tion of pivotal but previously elusive quality quartets as building blocks, and the application of an innovative and