To thrive for the highest possible integrity distinguishes pharmaceuticals from many other quality products that advance modern daily life, and this is reflected in multi-level regulatory pressure. Two parallel approaches seeks to address key expectations associated with this global consensus: (1) maximize reproducibility and traceability of the entire production workflow; and (2) employ rigorous, multi-level biological and chemical performance analysis throughout the process. The latter particularly builds on our ability to integrate STEM knowledge that is specific for the foundational disciplines of pharmacy: pharmacognosy, medicinal chemistry, pharmaceutical analysis, pharmacology, and toxicology. Being pillars of pharmaceutical integrity, their orchestrated use is essential for downstream clinical utility and fitness of the products for healthcare applications.

As collaborative approaches to science evolve and pharmacognosy projects often integrate 2-3 disciplines, recent advances in natural product (NP) research inspire the greater pharmacy community. The pharmaceutical term “purity” provides multiple entry points for discussion: purity has multiple and partially unclear facets; purity is of obvious importance when dealing with metabolomic NPs; and purity mounts into the recently established term Residual Complexity (RC), which can be understood as “deviation from total integrity and/or understanding”.

This presentation will discuss how foundational biological, chemical, physical, and mathematical principles affect the integrity of integrative pharmaceutical science. This includes examination of both prior and recently advanced foundational knowledge for a range of questions along the biology to mathematics continuum:

- What processes drive the discovery of new hits and the development of leads?

- Can NP hits be “too good to be true”?

- What is a “compound”, and how many structures does it have?

- What physiochemistry stands behind NP and API purification?

- How do overlapping chromatographic peaks differ from spectroscopic multiplets?

- Is methodological innovation the first objective or a last resort?

Discussion of potential answers will involve recent experimental evidence from our own work in the discovery of antibiotics, dental biomodifiers, bioactive principles from medicinal and dietary plants, and methodology for pharmaceutical integrity analysis. The overarching goal is to demonstrate how the application of fundamental knowledge is a prerequisite for integrative research and the further enhancement of the integrity of the pharmaceutical value chain.