Dr. Scott Gottlieb, the Commissioner of Food and Drugs, has outlined the steps the US FDA will take to implement the 21st Century Cures Act. In outlining the plan, the Commissioner endorses modeling and simulation approaches to increase the efficiency of drug development.
Certara has launched Phoenix® 8.0, the latest version of the innovative PK/PD modeling and simulation software used globally by researchers and drug developers in pharma, academia, and regulatory agencies. Many of the new features and functions that have been implemented in Phoenix 8.0 are based on valuable feedback received in a survey given to our Phoenix community. In a recent informative webinar and demo, Dr. Nathan Teuscher highlighted the new features and enhancements in the Phoenix WinNonlin® non-compartmental analysis (NCA) engine, NLME, Validation Suite, and the Phoenix workbench. This blog post summarizes the key topics covered in the webinar—for a detailed overview, watch the webinar and read the latest volume of The Phoenix Reporter e-newsletter.
Phoenix WinNonlin 8.0 - NCA を新たなレベルへ
Significant advances have been made to the Phoenix WinNonlin NCA engine, including the addition of new business rules for terminal slope (Lambda Z) which allows you to specify how it is calculated. This new feature includes the ability to specify the maximum number of points to include in the regression and the earliest time for samples to be taken. This setting is useful, for example, if you have a modified or extended release formulation and you want to ensure that the terminal slope is only calculated after a drug has been completely absorbed or absorption has stopped.
Another new feature in WinNonlin is the ability to automatically flag values that are related to Lambda Z that may or may not meet your standard operating procedure (SOP) criteria, including the adjusted R2, the observed or predicted % extrapolated area under the curve (AUC), and span (sampling interval/t1/2). The acceptance criteria display provides the ability to easily filter the subjects, or the profiles, that either meet or don’t meet the acceptance criteria.
One of the more beneficial enhancements in WinNonlin is the new NCA parameters for plasma and urine that have been added to the standard output. These parameters, commonly requested by global regulatory agencies, are now integrated into Phoenix, eliminating the need to use data wizards or other third-party tools to calculate them. Finally, users now can define custom NCA parameters, eg, those for computing concentrations used in interpolation methods, or other non-standard parameters such as half-Cmax value. The new plasma, urine and custom-defined NCA parameters minimize post-processing work and increase transparency with analysis.
Validation Suite 8.0 - Phoenix に統合された WinNonlin の高速バリデーションツール
As required by US FDA’s 21 CFR Part 11, the International Conference on Harmonization of Technical Requirements (ICH), EudraLex Annex 11, and other regulatory agency guidance documents, computer systems used in the pharmaceutical industry, and output from software used in regulatory submissions must be validated to assure proper performance. This requires significant time and resources to manually write and perform the validation steps used in software execution. Phoenix WinNonlin Validation Suite 8.0 provides objective evidence of Phoenix WinNonlin 8.0 functionality. マウス操作を通して実行可能な自動化テストと各種バリデーション文書テンプレートの提供によってバリデーション業務を合理化します。
Phoenix NLME 8.0 - 自動並列計算機能と遅れを伴うアウトカムをモデル化する分布型の遅れを表現する関数
Two major enhancements have been made in Phoenix NLME 8.0: リモートグリッド計算環境における自動並列計算機能と分布型の遅れを表現する関数の2種類の関して、大幅な改良が加えられています。NLME parallelization feature is available for most run modes and offers the ability to run on powerful remote compute platforms, reducing run times from days to minutes. The new distributed delay function, is useful for modeling delayed outcomes in therapeutic areas such as oncology, diabetes, and arthritis, and simplifies coding delays in PK/PD models.
The ability to run NLME jobs on remote grids for two scenarios directly from the desktop application was introduced in Phoenix 7. NLME 8.0 has been expanded to execute all scenarios in parallel across the maximum possible cores, and supports all NLME run modes except Sim/Predictive Check. Two types of parallelization are also included: between model parallelization, which allows for running all models simultaneously in parallel on different processors, and within model parallel action using computation grids where the analysis work for one model can be divided between several CPUs. The two types of parallelization approaches can also be combined, enabling models to be run in parallel and on multiple cores, reducing run times by 80-90%. This enables completion of analysis and scientific exploration in real time, allowing scientists to revise their hypothesis, if necessary, and move to the next step.
Regardless of the approach, no intervention or user input is needed to execute a model on a grid—Phoenix will automatically determine the optimal number of cores needed to run the model in the minimal amount of time. For any run mode, NLME considers type of run mode (simple +/- sort, scenarios +/- sort, covariate search, boot-strap), the number of subjects, models, and the number of available cores, to determine the optimal core utilization.
Phoenix NLME can also be paired with Certara’s Burstable Compute Grid, which offers access to up to 1,800 cores with just one click, accelerating model runs affordably and without IT support—reducing the time to complete projects in hours or even minutes versus days.
Phoenix 7 introduced simplified coding for discrete delay differential equations. NLME 8.0 has been expanded to include a distributed delay function. This methodology can be used to replace transit compartments, dual absorption models, effect compartment models, or even indirect response models, providing a more accurate evaluation of physiological or pharmacological systems with time delays. The integrated discrete and distributed delay functions are automated, eliminating the need for complex coding. A delay function can be added with a single Phoenix Modeling Language (PML) command, avoiding inefficient workarounds and approximations.
Phoenix の基本機能 - PK/PD解析の生産性向上と QA/QC を支援する新機能
Several Phoenix workbench enhancements facilitate conducting PK/PD analysis as well as QA/QC efforts. The new framework applies across all Phoenix applications—WinNonlin, NLME, IVIVC—and includes the ability to lock workflows, increased flexibility for object settings, and integrated local license activation that eliminates the need for licensing wizards.
Want to learn more about the new features in Phoenix 8 and other PK/PD approaches to drug development including NCA, non-linear mixed effects (NLME) modeling, and in vitro-in vivo correlation? Check out Certara University, which provides in-depth classroom and online courses to enhance your knowledge, expertise, and skill in modeling and simulation strategies.