Design & Simulation / Reaction & Synthesis

Simulation Project Targets Biopharma Process

Software aims to address process knowledge gaps and speed time to market

By Seán Ottewell

Software could replace costly laboratory and pilot-plant trials for scale-up.

A researcher at the Technical University of Graz (TU Graz), Austria, has won funding from the Austrian Research Promotion Agency (FFG) to commercialize his work simulating biopharmaceutical processes.

Christian Witz, researcher with the Institute of Process and Particle Engineering at TU Graz, shares the €3.4 million ($3.76 million) pot with eight other projects selected by an international jury from a field of 26 for funding from the FFG’s spin-off fellowship program. This aims to develop intellectual property held in the country’s universities and research institutions. The nine latest projects join 24 other spin-off fellowships that already have won funding.

In Witz’s case, the funding will help him set up a company to further develop and market the software he and his co-researchers created as part of the Institute’s Computational BioProcess Design (ComBioPro) project.

“At the moment, the biotech industry lacks in-depth process knowledge. People know that the manufacturing process works, but they don’t know the reasons why or how exactly it functions,” says Witz.

One of the main challenges, he adds, is that the simulation programs currently available need substantial computing power, software expertise to manipulate, and take months to perform the necessary calculations.

However, a new in-house code developed during the project enables realistic simulations of complex industrial-scale devices used in engineering processes. Originally developed for aerated and stirred-tank reactors, it now can find, test and interconnect “highly efficient” algorithms to graphic processing units (GPUs) to simulate the physical process inside devices such as bioreactors.

Possible customized applications include the movement of the fluid flow field, bubbles, particles, droplets, species and microorganisms as well as the device geometry including stirrers, heat exchangers, porous zones and sensors. Using metabolic models enables inclusion of the biological activity of the microorganisms.

As part of the ongoing work, Witz will integrate further algorithms into the software, which will allow for even more exact and user-friendly representation of physical and biochemical processes in bioreactors.

Among other things, the aim is to partially automate the evaluation of raw simulation data, and to simulate very large air bubbles in a reactor. The simulation results will ultimately feed into decision-making processes for design and production. In turn, this would enable companies to simulate more projects in a shorter time and carry out tests showing where and how productivity losses occur in a reactor.

“My system will cut simulation times from months to a matter of hours. It can be operated by people without simulation know-how and runs on standard commercial graphic cards,” notes Witz.

The new software shortens the time needed for troubleshooting and promises more detailed insights into processes. This will help to make biopharmaceutical manufacturing more efficient.

Witz identifies three main market benefits to the software: replacement of costly laboratory and pilot-plant trials for scale-up, or deviation management; acceleration of market launches of new products; and in support of regulatory approvals for state-of-the-art drugs.

Using scientific methods enables replacement of trial and error and minimizes millions in losses. Thus, he says, the object of the company is also to be an important building block in the digitalization of a rather conservative industry and build on the trend toward Industry 4.0.

“Companies need to perform fewer experiments to make the step from the lab-scale to industrial-scale production. Savings in the development [of each new drug] are estimated to be between €300,000 ($331,000) and €1 million ($1.1 million),” says Witz.

Biopharmaceuticals is a huge and rapidly growing business. According to market analyst Mordor Intelligence, the global market for biopharmaceuticals in 2018 exceeded $237 billion. Moreover, this should rise to over $388 billion by 2024 — a compound annual growth rate of nearly 9%. Biopharmaceuticals already account for seven of the top-selling medications in the world.

However, they are also more expensive to make than chemical drugs such as the disease- modifying anti-rheumatic drugs (DMARDS). The materials needed cost more and manufacturing processes that rely on live organisms are more complex. R&D costs are higher, too.

This is illustrated by the U.S. Food and Drug Administration’s approval in May of Zolgensma to treat spinal muscular atrophy — a rare disease in infants. This one-time gene therapy treatment is manufactured by Novartis and — at $2.1 million for each use — becomes the world’s most expensive drug following its approval.


 

Ottewell2Seán Ottewell is Chemical Processing's Editor at Large. You can email him at sottewell@putman.net.

 

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