Alotaiq Nasser, Dermawan Doni
Health Sciences Research Center, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11432, Saudi Arabia.
Department of Applied Biotechnology, Faculty of Chemistry, Warsaw University of Technology, 00-661 Warsaw, Poland.
Pharmaceutics. 2024 Nov 3;16(11):1414. doi: 10.3390/pharmaceutics16111414.
BACKGROUND/OBJECTIVES: The rise of virtual bioequivalence studies has transformed the pharmaceutical landscape, enabling more efficient drug development processes. This systematic review aims to explore advancements in physiologically based pharmacokinetic (PBPK) modeling, its regulatory implications, and its role in achieving virtual bioequivalence, particularly for complex drug formulations.
We conducted a systematic review of clinical trials using computational methods, particularly PBPK modeling, to carry out bioequivalence assessments. Eligibility criteria are emphasized during in silico modeling and pharmacokinetic simulations. Comprehensive literature searches were performed across databases such as PubMed, Scopus, and the Cochrane Library. A search strategy using key terms and Boolean operators ensured that extensive coverage was achieved. We adhered to the PRISMA guidelines in regard to the study selection, data extraction, and quality assessment, focusing on key characteristics, methodologies, outcomes, and regulatory perspectives from the FDA and EMA.
Our findings indicate that PBPK modeling significantly enhances the prediction of pharmacokinetic profiles, optimizing dosing regimens, while minimizing the need for extensive clinical trials. Regulatory agencies have recognized this utility, with the FDA and EMA developing frameworks to integrate in silico methods into drug evaluations. However, challenges such as study heterogeneity and publication bias may limit the generalizability of the results.
This review highlights the critical need for standardized protocols and robust regulatory guidelines to facilitate the integration of virtual bioequivalence methodologies into pharmaceutical practices. By embracing these advancements, the pharmaceutical industry can improve drug development efficiency and patient outcomes, paving the way for innovative therapeutic solutions. Continued research and adaptive regulatory frameworks will be essential in navigating this evolving field.
背景/目的：虚拟生物等效性研究的兴起改变了制药格局，使药物研发过程更加高效。本系统评价旨在探讨基于生理的药代动力学（PBPK）建模的进展、其监管意义以及在实现虚拟生物等效性方面的作用，特别是对于复杂药物制剂。
我们对使用计算方法（特别是PBPK建模）进行生物等效性评估的临床试验进行了系统评价。在计算机模拟和药代动力学模拟过程中强调了纳入标准。在PubMed、Scopus和Cochrane图书馆等数据库中进行了全面的文献检索。使用关键词和布尔运算符的检索策略确保了广泛的覆盖范围。在研究选择、数据提取和质量评估方面，我们遵循PRISMA指南，重点关注美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的关键特征、方法、结果和监管观点。
我们的研究结果表明，PBPK建模显著提高了药代动力学特征的预测能力，优化了给药方案，同时减少了大规模临床试验的需求。监管机构已经认识到这种实用性，FDA和EMA制定了将计算机方法纳入药物评估的框架。然而，研究异质性和发表偏倚等挑战可能会限制结果的普遍性。
本综述强调了制定标准化方案和强有力的监管指南的迫切需求，以促进虚拟生物等效性方法融入制药实践。通过采用这些进展，制药行业可以提高药物研发效率和患者治疗效果，为创新治疗方案铺平道路。持续的研究和适应性监管框架对于驾驭这一不断发展的领域至关重要。
