2022 Franz Edelman Competition: Merck Animal Health

Ashley Kilgore:

This podcast is part of a special series featuring the 2022 finalist teams for the INFORMS Franz Edelman Award for Achievement in advanced analytics, operations research, and management science, the most prestigious award for achievement in the practice of OR and advanced analytics.

Ashley Kilgore:

For more than four decades, the Edelman Award has recognized contributions that are transforming how we approach some of the world’s most complex problems. Finalists for the Edelman award have contributed to a cumulative impact more than 306 billion dollars since the award’s inception, as well as countless other non-monetary benefits.

Ashley Kilgore:

The winner of this year’s award will be announced at the 2022 INFORMS business analytics conference held April 3rd to the 5th in Houston, Texas.

Ashley Kilgore:

Joining me for this episode, our PK Yegneswaran, vice president of manufacturing science and technology, and Oscar repping executive director of biotech solutions to discuss the finalist entry from the team at Merck Animal Health.

Ashley Kilgore:

Merck Animal Health offers veterinarian, farmers, pet owners, and governments one of the widest ranges of veterinary pharmaceuticals, vaccines and health management solutions. After four years of collaboration where vision met opportunity, a portfolio of optimization and decision support applications were implemented that substantially improved biomanufacturing effectiveness.

Ashley Kilgore:

Biomanufacturing uses living organisms, such as viruses and bacteria to grow active ingredients in vaccines and therapeutics. This high tech manufacturing process generates challenges not found in many other industries. Additionally, the high cost of equipment and labor intensive nature of operations preclude the ability to just add capacity. Operations research played a critical role in helping Merck Animal Health increase the output of critical medicines in specific areas.

Ashley Kilgore:

PK, Oscar, thank you both for joining me. I’m really looking forward to discussing your team’s work.

PK Yegneswaran:

Great. And thank you for having us.

Oscar Repping:

Thank you for having us.

Ashley Kilgore:

Could you start us off by sharing a bit more about the work conducted at Merck Animal Health, particularly in the area of biomanufacturing?

PK Yegneswaran:

Yeah, sure, I can. So the project began with a clear version of increasing the output of our production facility without increasing capital investments with a transformation towards smart or operations that proactively use data analytics and operations research in our daily decisions. But critical to this success was harnessing the power of using operations research methods and operations management concepts to complement life sciences knowledge, and the word was done in close col collaboration with the school of industrial engineering at the OV university of technology. And this is based in the Netherlands five years into collaboration. We developed a portfolio of optimization models and decision support tools to meet this goal focused two areas, the first one being improving bioreactor yield, and the second one improving the end-to-end Fe visibility and scheduling.

Ashley Kilgore:

Now, what are some of the challenges associated with biomanufacturing?

PK Yegneswaran:

So in the conventional pharmaceutical manufacturing, the medicines are chemically synthesized and in contrast, biomanufacturing uses living organisms to make the active ingredient. And these living organisms could be viruses, bacteria, or even parasites. And many of these organisms are grown in bioreactors that contain specialized cell culture media, and are operated with precision controls. And by using these living organisms, we can create highly complex and innovative drugs. However, the use of these organisms generate high levels of uncertainty and batch to batch variability in production yield, lead times, but also cost at all stages of the value manufacturing processes.

PK Yegneswaran:

Any the complexity is not limited to the growth of the active ingredient in the bioreactors itself. The downstream process of filtration and purification require precision and timing too.

PK Yegneswaran:

A single medicine will contain 4,000 to 8,000 interconnected steps. The no weight constraint means that once the back is released in the shop floor, it cannot wait in between the production steps. And this requires precise orchestration of the steps. And all challenges in the industry include long set of times, the use of costly raw materials and agents, which have a high batch to batch for variability, the limitations in highly specialized equipment and resources, the high risk of failures and the uncertainties in lead time and cost.

PK Yegneswaran:

Additionally, diversity among the items produced add to complexity. And in one of our box mail facilities, we produce over 60 active ingredients across multiple process lines, which drives a need to coordinate production activities with demand. And to be successful we need to establish an end-to-end feasibility and an effective scheduling approach. The old manual approach would not scale up for the next challenge although there were certainly lessons to be carried forward.

Ashley Kilgore:

Could you share what your approach was to create a new solution to address these challenges?

PK Yegneswaran:

Yes, definitely. And inspire by the unique challenges of biomanufacturing operations, we developed a portfolio of models and decision support tools to support, improve bioreactor yield and orchestration of the manufacturing steps. The starting point was a process to capture and store all critical manufacturing information and to build confidence in these models. And the operations research methods used include stochastic optimization, busy and design of experiments and simulation optimization.

PK Yegneswaran:

And for example, we developed a mark of decision process that helped us to reduce the bioreact set of times and we called it breed feed and the MDP model linked the underlying biology of cell processes with operational tradeoffs and businesses.

PK Yegneswaran:

And in another project, we used [inaudible 00:09:32] learning to identify an optimal configuration of critical process parameters to maximize the bioreactor yield.

PK Yegneswaran:

And in the third project, we adopted a simulation based optimization approach with an extensive effort to institutionalize the collection and storage of manufacturing, specification information to assist our scheduling decisions, both on the shore and long term.

Ashley Kilgore:

And what was unique about this solution?

PK Yegneswaran:

Yeah, great question. And as a unique feature, our approach connects operation research and life sciences. The life science literature mostly focus on the underlying biological dynamics of biomanufacturing processes. And the connective models describe how the fermentation process evolve over time. However, these connecting models were highly inadequate to support our business decisions and financial trade off, which especially with the inherent variability in the core manufacturing process.

PK Yegneswaran:

We have synthesized life science with operations research, which actually takes key business and production trade offs into consideration. And this synthesis was critical to boost manufacturing outputs and create impact.

PK Yegneswaran:

The application of operation research is relatively new to the bio manufacturing industry and perhaps due to the initial challenges of basic mastery of the core technology. There are only a limited number of research paper and a few written accounts of success in the operation research literature.

PK Yegneswaran:

And we certainly will do our work to stimulate new studies at the intersection of operations research and biomanufacturing. Moreover, we believe that our work will significantly help the industry provide fast and affordable access to critical medicines for both humans and animals.

Ashley Kilgore:

Since implementation what has the impact been for Merck Animal Health’s operations and output?

PK Yegneswaran:

The models and decision support applications are used regularly in our operations and have generated significant positive impact. The bioreactor configuration application, for example, relies to 30% to 50% implement in batch yield and a 20% reduction in the standard deviation. The bleed feed application developed here achieved around 80% higher yield per bioreactor cell. The application focused on the end-to-end visibility identified that one additional batch could be produced per week, per production line without any additional risk resulting in increased capacity.

PK Yegneswaran:

We also realized several non monetary soft benefits. Transformation of our culture, for example. Prior to this project, operational decisions were primarily made based on domain expertise. With this project data analytics and operations research started to have a more prominent role in our daily decisions. Consequently, we are now able to develop this new operations research capability within Merck Animal Health. We were also able to have increased flexibility in manufacturing and scheduling to better respond to changing demand patterns in the marketplace. We were also able to lower our CO2 emissions and enhance our carbon footprint as a result of higher bioreactor throughput.

Ashley Kilgore:

And, in turn, for those who benefit from access to these increasingly effective vaccines and therapeuticals, what has the impact been for them?

PK Yegneswaran:

We now have the concept of one health in integrated approach to health of humans, animals, and the environments we live in. This work contributes to increasing access to life saving drugs and better risk wants to market needs.

PK Yegneswaran:

The animal health industry is currently experiencing substantial challenges to meeting the market demand worldwide. Therefore, every unit produced has a significant contribution towards responding to the market needs and the one health concept. Caring for animals is also critical to improve the health and well-being of humans. A recent report published by the world health organization estimates that 61% of all human diseases are zoonotic in nature. Meaning they travel from animals to humans. This emphasizes the critical role of our industry in maintaining the health and welfare of humans and animals together. By using advanced analytics and operations research, we are now able to increase our biomanufacturing efficiency and thereby improve the availability and accessibility of lifesaving drugs. Together, we can make this world a better place for all.

Ashley Kilgore:

PK and Oscar, I want to thank you, again, for joining me and wish you and the rest of your team good luck in the 2022 Franz Edelman competition. Are there any final thoughts you’d like to share regarding your team’s finalist project?

PK Yegneswaran:

Yeah. Sure. Thank you. The applications we described have had initial success and already the process of being transferred and scaled to other production facilities. We are confident that this process of scaling out will continue to be successful. This work has demonstrated the general nature of solution set and will serve as a foundation, an example of value in linking operations research with life sciences in bio manufacturing, which will drive substantial and sustainable productivity improvements across our company and beyond. Thank you.

Ashley Kilgore:

Want to learn more? Visit resoundinglyhuman.com for additional information on this week’s episode and guests. The podcast is also available for download or streaming from Apple podcasts, Google Play Stitcher and Spotify. Wherever you listen, if you enjoy Resoundingly Human, please be sure to leave a review to help spread the word about the podcast.

Ashley Kilgore:

Until next time, I’m Ashley Kilgore. And this is Resoundingly Human.