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www.biopharminternational.com Quality and Regulatory Sourcebook eBook March 2024 BioPharm International ® 17 Quality by Design ment system known as Knowledge-aided Assessment and Structured Application (KASA) (6). In addition to risk assessments, digitalization of other QbD workflows (1) using tools like iRISK can offer up sim- ilar benefits and drive improved integration of activities for the development of a product and across different products. For example, QTPPs, process design selections, identification of CQAs, and summaries of parametric and attribute control all have elements that can be digitalized and integrated with risk assessments, because they lever- age a common digital product profile (a digitalized master version of product and process definition details, includ- ing process recipes, parameter and attribute information, and key control strategy information). Beierle et al. (13) highlight the challenges associated with the lack of global regulatory harmonization of control strategies which present a hindrance to the acceleration of innovative therapeutics for millions of patients around the globe for unmet medical needs. Additionally, the abil- ity to continually improve the pharmaceutical manufac- turing process (14) and analytical procedures (15–17) can be impeded by regulatory authorities adopting different approaches for assessing post-approval changes. While driving towards a global harmonized regulatory control strategy is aspirational and desirable, different approved versions of the control strategy across multiple regulatory regions will continue to be a challenge for pharmaceutical companies to manage across the lifecycle for the foresee- able future. The use of digital risk assessments via tools like iRISK provides new opportunities for managing these often subtly different approved control strategies across different regulatory regions in a more effective manner. As industry adopts the Q12 concept of identifying ECs, tools like iRISK can be leveraged to manage possible ad- ditional regional differences. Benefits for technology transfer Across product and process development, information is generated and transferred between R&D and manufac- turing in standard data forms and/or across disparate systems. This leads to high data search times followed by inconsistencies and non-contextualization of key data. During tech transfer, long discussions are often needed to agree on process and analytical procedure recipe terminol- ogy across donor and receiver sites. Digital transformation involves improved new digital tools and business practices to enable efficient tech transfers. A new digital backbone, in the form of integrated data pipelines between digital systems within the CMC ecosystem (Figure 3), will enable faster flow of information across the tech transfer donor and receiver sites. In addition, standardized business pro- cesses such as Enterprise Recipe Management (ERM) will ensure product and process information are described consistently across all sites and groups involved in tech transfer. The wider approach to ERM will enable multiple users to define the product, process, and analytical pro- cedure characteristics in a structured framework within a digital ecosystem. Future integration of ERM with man- ufacturing execution systems will open up many oppor- tunities for automation and execution of the operational control strategy. Combined with the integration of digital QbD workflows, such as the risk assessments as explained in this article, this digital ecosystem will enable data (once defined) relating to the product control strategy to be gov- FIGURE 4. Example risk visualization outputs from iRISK (risk heat map and process risk mapping for "A-Mab" drug substance [DS] early-stage quality-by-design [QbD] risk assessment).