Issue link: https://www.e-digitaleditions.com/i/1481708
8 Pharmaceutical Technology ® Trends in Formulation 2022 eBook PharmTech.com Development safety) involves the combination of an appropriate mix of studies pulled together by drug discoverers and drug developers. "The appropriate screening cascade will create the opportunity to reduce the attrition of the drug candi- date during the pre-clinical phase. The same concept applies when the PDC moves into the clinical devel- opment phase," Maraschiello says. In t he clinica l development phase, t he transla- tional approaches supported by data management and statistics are the key to correctly designing clin- ical trials with back-and-for th loops bet ween the pre-clinical and clinical phases, Maraschiello adds. Early screening goals To optimize early drug candidate screening results, goals must be firmly established. For instance, it must be clear from the start which type of patient population is the target. "From the start" means that, at the very early stages of drug discovery, a clear tar- get product profile and a defined regulatory strategy plan must be in place when an R&D process is started, according to Maraschiello. From t he s t a r t i ng poi nt , a de ve lopabi l it y a s- sessment must be established, which occurs at the lead optimization stages, where a compound or a se- ries of lead compounds are thoroughly tested for their potential to become a therapeutic product. In the case of advanced therapy medicinal products, market access con siderat ion s a re even more i mpor t a nt and must happen early in the R&D process, empha- sizes Maraschiello. "Consequently, what is important is not the quan- tity but the quality of the molecules because of an in- telligent screening based on the premises mentioned above," says Maraschiello. Facilitating speed-to-market success The ideal early screening strategy encompasses two key goals: high throughput and high-qualit y hits, according to Tiago. Such an approach speeds the route to market in two main ways: by having a larger pool of candidates that can weather later waves of attrition without being fully depleted, and by min- imizing the time and resources spent progressing sub-optimal candidates. The insight needed to drive hit quality requires sensit iv it y a nd per for ma nce t hat isn't ava i lable with many current instruments and methods, Tiago points out. "Extracting such insight at scale generates unfath- omable volumes of data that can paralyze analysts," Tiago states. GCI helps by providing binding kinetics informa- tion in a single method at the initial stages of screen- ing, allowing researchers earlier—and deeper—in- sight i nto how t he ca nd idate m ight behave i n a biological system. In the end, this process leads to better decision-making and eliminates the need for successive and distinct affinity and assay screens, which can have contradictory results and can be ex- tremely time intensive. "GCI data analysis is being streamlined with auto- mated platforms to speed analysis while increasing accuracy and reproducibility. These automated tools are tackling the speed-to-market challenge by reduc- ing the impact of skilled labor shortages and miti- gating the risk of later-stage issues owing to human error or unreliable analysis results," Tiago explains. Successful early candidate screening means the successful nomination of a high-quality pre-clinical drug candidate, emphasizes Maraschiello. "Quality here is defined as an enhanced probability of success dur ing t he pre-IND phase," according to Maraschiello. Maraschiello explains that when an appropriate screening cascade is conjugated with a late-optimiza- tion-phase design to de-risk the selected compounds before they enter the regulatory pre-clinical develop- ment phase, the process either ensures the selection of an IND-ready candidate or can lead to the early termination of a selected drug candidate where the impact of cost and time is made clear at the outset. Another important factor in a successful drug candi- date screening process is the ability to integrate "de- velopment thinking" into the discovery phases and to develop translational approaches aimed at optimiz- ing the clinical trial designs, says Maraschiello. This approach ultimately increases the odds of a success- ful Phase III clinical trial, Maraschiello points out. Ultimately, silo thinking and sequential decisional processes within the R&D va lue chain should be abandoned, Maraschiello states. " Wit h t he tec h nolog ies at h a nd a nd w it h t he multi-disciplinary character of the R&D process, it is increasingly difficult to keep working in data silos either in discovery or in development and between both phases. The R&D process is not a sequential pro- cess anymore; it is a virtuous circle going back and forth through the entire value chain to increase the productivity of the R&D process," Maraschiello says. Where the drug discover y and candidate screen- ing process was dif f icult 10 years ago, nowadays, the industry has the increased aptitude to manage pre-clinical and clinical data, which creates a pow- erful translational and predictive process with the sole purpose of reaching the patient faster and better, Maraschiello adds. Meanwhile, Tiago notes that, aside from quality and throughput challenges, the one thing hurting and frustrating drug developers more than anything else is the late-stage failure of a candidate that has