Biopharma and numerical modeling: experience and practice of Amgen
In the biopharmaceutical industry, as in any modern high-tech industry, the methods and tools of numerical modeling of physical and chemical processes are increasingly used to solve a wide variety of problems, from the development of new dosage forms and methods of their production to the analysis of the processes of transportation, storage and delivery of drugs .
Amgen is one of the leading biopharmaceutical companies in the world. The drugs of this company help millions of people suffering from serious diseases. Each medicine is a product of painstaking work of scientists, engineers and technologists. Specialists of Amgen use multifimetric modeling as a tool that allows to ensure the efficiency and safety of all stages of production. Due to the specific nature of the problems arising in this industry, it is very often necessary to deal with the modeling of complex physicochemical processes, so the availability of a wide range of mathematical models in software for numerical simulation is a key factor.
Pablo Rolandi, director of production processes at Amgen, analyzed how the company's specialists use the COMSOL Multiphysics simulation environment. ® to solve the problems facing them.
In this video, we talk about the COMSOL application development environment, which allows you to create easy-to-use applications with the necessary graphical interface on the basis of computational models and provides an opportunity to expand the functionality of the numerical modeling environment by writing additional procedures and scripts.
Optimization of technological processes
One of the areas in which the Rolandi group applies numerical modeling tools is the optimization and elimination of "bottlenecks" in production processes. As an example of successful implementation of modeling results, the task of intensifying the drying process can be cited. The problem arose when the company abandoned the services of a contract organization and moved production to its own factory in Singapore. It turned out that the capacity of the filter drier, in which moisture removal and separation of components is performed, is too low, which increases the risk of unmet demand for the final product. Rolandi's group was puzzled by the construction of a computational model, with which it would be possible to find bottlenecks and optimize the drying process. Since the technological process is multi-stage, and the first three stages previously used a different type of equipment, Amgen specialists did not have enough data on the characteristics of the dryers, which made it impossible to create an accurate model and to determine how productivity was affected by the changing conditions for drying. First of all, it was necessary to evaluate the effect of two critical parameters, the rate of evaporation and diffusion in the new dryer. Specialists had to calculate a large set of data and use regression analysis to process them to get all the characteristics of the model. Based on the developed computational model COMSOL, an easy-to-use application was created in which it is possible to calculate the time required to complete a complete drying cycle.
Application for calculating the drying time under various process conditions. The application provides for the possibility of comparing the calculation results with the experimental data
This application was used by engineers-technologists, adjusting the equipment and production processes. The application allows users to assess the impact of changing equipment operating conditions and take measures to increase its productivity.
Solving inverse problems using optimization methods in COMSOL Multiphysics [/b]
In this video, We present an overview of the capabilities of the COMSOL Multiphysics package optimization module. ® and on the example of three inverse problems - heat conduction, conjugate heat transfer and chemical kinetics, we show how to adjust the computational model.
Providing high standards of sterilization
Another example of a successfully solved problem with modeling is compliance with sterilization standards for shipping containers. Medicinal preparations from the factory are transported in special containers, which must be sterilized in accordance with strict requirements of the relevant standards, because any, even slightly bacterial contamination of the drug can lead to very unpleasant or even dangerous consequences. The standard sterilization procedure with ethylene oxide was not suitable for new containers and it had to be corrected. The Rolandi group proposed to analyze the process of diffusion of ethylene oxide in new containers using numerical simulation, which avoided numerous costly experiments. An application was developed in which the user could specify the contamination penetration area, indicate solubility, diffusion constants and calculate how the ethylene oxide concentration in the container changes over time.
Application for modeling the sterilization process, in which the change in the concentration of ethylene oxide in a container is calculated over time
Technologists used the application to select the optimal concentration of sterilizing agent for specified conditions in a container of a certain geometric shape. The implementation of the application significantly reduced, and in some cases even eliminated the need for experiments, which in turn, for several months, shortened the design phase and the cost of the experiments. "It turned out that creating applications for numerical modeling is much more effective," says Rolandi.
Modeling of chemical reactors in COMSOL Multiphysics [/b]
In this video, we tell you how to simulate the processes in chemical reactors of various types in COMSOL Multiphysics ® . The video discusses the modeling of transport processes and the kinetics of chemical reactions in flowing, porous reactors and mixing reactors.
Not only the simulation of
"I think not only about numerical modeling, but also about the development and integration of the most advanced applications and methods," says Rolandi. "I believe that we have a strategic task ahead of us, and we have just begun to address it." One of the problems to be solved is taking into account the uncertainty (error) of the input data. In practice, the input parameters of any problem are rarely specified accurately, they are all characterized by some error. To increase the reliability and usefulness of modeling, these errors must be taken into account.
For example, the Rolandi group is working on creating a model of an automatic injector - a device for administering a drug in an automatic mode without the participation of a doctor. The most important parameter of the device is the time of drug delivery. This parameter needs to be closely monitored in order to strictly observe the prescribed dosages of the medication prescribed by the physician. The difficulty is that the delivery time is determined by a number of parameters known with varying accuracy - these are the geometric dimensions and shape of the container, the density and viscosity of the preparation, the friction coefficient for the piston in the injector, etc. If the error of these parameters is not taken into account, then it is impossible to determine the dispersion for the drug delivery time, and without this characteristic it can not be precisely controlled. As a result of simulation, it is important to obtain a distribution of the probabilities of the result, this will allow a better analysis of the performance of the entire system as a whole.
To analyze the sensitivity of the delivery time to different initial parameters, the specialists from the Rolandi group used the tools of multi-physical modeling, with the help of which they calculated the sensitivity index for each parameter of the problem. For example, they found that the viscosity of the preparation and the geometric dimensions of the needle determine a 90% dispersion for the delivery time, while the remaining parameters account for the remaining 10%. This made it possible to substantially simplify the model, since only a few parameters have a significant effect on the delivery time. In turn, this knowledge facilitated the preparation of terms of reference for component suppliers and reduced the risk of errors.
The application for modeling the automatic injector, which calculates the error of the delivery time of the drug
Like other computational models built in COMSOL Multiphysics ® , the model for analyzing the delivery time of the drug was turned into a convenient and easy-to-use application in which users can view the documentation, specify the initial data, perform an error analysis and automatically generate reports on the performed calculations. Implementing the application again saved time and money for research.
Analysis of the sensitivity of the model to the initial data [/b]
In this video, we describe how to use the sensitivity analysis function of the model to its input parameters. On fairly simple examples, we demonstrate the key settings of the calculation model and show how to perform the sensitivity analysis for modeling various physical processes.
Deploy and distributeapplications.
Amgen uses the local version of COMSOL Server TM to make the applications available to their employees. "We want all Amgen employees to use our applications," says Rolandi. - I am proud that at the moment the company is actively using more than ten applications. The introduction of such technologies became possible only through the use of the COMSOL environment. "
COMSOL Server TM It makes it very easy to deploy, administer and use applications both internally and externally via the Internet. Users can simply log in through a regular web browser and access the application library developed by the Rolandi group.
The Amgen application library developed by the Rolandi group
Rolandi Group is not going to stop there and plans to integrate its applications into the technological process, for example, to automate the input of initial data, and turn the applications into the "computing core" of the company's information system.
Fundamentals of solving differential equations defined by the user [/b]
In this video, we will show how to use algorithms and unique modeling tools COMSOL Multiphysics ® for solving arbitrary systems of algebraic and differential equations and for modifying existing physical interfaces.
Speech by Pablo Rolandi at the COMSOL 2017 User Conference
Interesting articles on the topic from the blog COMSOL
Optimization of biopharmaceutical processes using numerical simulation
Analysis of fine chemical synthesis in plate reactors
More examples of using COMSOL ® research teams from ASML, TAUW, NRC, Endress + Hauser, Sintex, Amgen, TUM, EPFL, NTS, etc. can be found in the issue of journal COMSOL NEWS 2018 in Russian.
Summary of COMSOL NEWS 2018 [/b]
Multifimical modeling in the manufacture of microcircuits. ASML, Netherlands
Modeling of multiphase flows in treatment plants. TAUW, The Netherlands
Modeling in the field of biopharmaceuticals. AMGEN, USA
Reducing the risk of galvanic corrosion in aluminum structures. National Research Council of Canada
Development and analysis of non-contact magnetic couplings. Sintex, Denmark
Optimization of acoustic flowmeters. Endress + Hauser, Switzerland
Applications for modeling and research in the field of tribology. The Mechanism Research Center (FZG) of the Munich Technical University (TUM), Germany
Numerical simulation of acoustic metasurfaces. EPFL, Switzerland
Improving the efficiency of sintering iron-containing ores. Industrial Research Institute of the German Metallurgical Society, Germany
Optimization of the construction of passenger cars using modeling applications. Mahindra Two Wheelers, India
-Multiphysical modeling on protection of wind turbines from lightning. NTS, USA
And we invite all comers on November 1 to the main event for present and future users COMSOL - day COMSOL in Moscow .
What is COMSOL Day in Moscow 2018 [/b]
Free of charge in the center of Moscow we talk all day about modeling in COMSOL
A lot of active users of the package in one place share experience and knowledge
COMSOL engineers respond to tricky questions
Invited papers from leading science-intensive and innovative organizations of Russia
Program of 4 mini-courses: Mechanics, Electrical Engineering, Inverse Problems and Automation
Coffee, cookies and multiphysics
Free registration and the full program at .
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