Day 1: Don’t try this at home, or in GMP (try it at the Testa Challenge!)

Like most systematic approaches, a failing cog, loose wiring or a single broken piece can cause the whole process to come to a halt. The same principle applies to bioprocess manufacturing. Thinking ahead and preparing for many months in advance, we have put several mitigations in place to keep the process going throughout the Testa Challenge week. We knew we were taking on a huge task and perhaps biting off more than we can chew, but no one could have ever been ready for what we were about to face. But the Testa Challenge is called a challenge for a reason.

October 19^th 2020. It was a much colder morning than usual in Uppsala, colder than it had been in a long time in fact. The participants had arrived and were seated in the Testa Center ready to be taken through the safety regulations in order to begin their work in the labs. Things were slowly heating up…. everyone knew what they came here for, everyone was eager to start, everyone was excited.

It was now getting quite warm at the Testa Center. Cytiva staff and experts were at the ready and all the necessary lab preparations were complete to kick off the experiments as well as give a helping hand to the participants.

First in the lab was Fredrik Petersen, co-founder of atSpiro, starting up their ShakeReactor, a shake flask bioreactor, in the Kuhner SFI-XC shaker. Our first challenge of the day was the speed and stability of this step. Not having had access previously to a standard industrial shaker with a large throw diameter, this was a learning for atSpiro. If the flasks are not secured properly or the shaker would be set at too high RPMs, the flask could fall over due to the new weight distribution of flask and ShakeReactor. After a brainstorm and while maintaining a cool head, the atSpiro team with the experience and well as intuition of Andreas Anderson, the project technical lead, realized what  adjustments need to be made. Adding further securing measures and lowering the RPMs the flask was securely fastened and ready to operate optimally.

Within the next hour we faced our next hurdle: the integration of the sensor-ball innovation from Freesense into the sterile GMP-graded single-use bioreactor bag. To accomplish this, we needed to cut open the bag and insert the sterilized sensor-balls. Patricia Roch, an expert from Cytiva, was overseeing this task as well as the complex procedure of re-sealing the bag using a heat gun. With much concentration and skilled hands, Patricia only had few words of wisdom while bringing the bag back into operational conditions under the sterile laminar flow hood, “Don’t try this at home, or in GMP”.

"Don't try this at home, or in GMP."

Patricia Roch, 2020

After five minutes the Testa Center certainly became one of the hottest places for Andreas as his face turned white and sweat was building up on his forehead. There were incorrect readings coming from the pH-probe and error messages. This could put the whole cell culture in jeopardy and would be a catastrophe for the Testa Challenge and Freesense’s data.

Or so we thought. After closer inspection, we found out that we needed to reset the pH-probe. With a swift and easy hand Andreas reset and recalibrated the pH-probe. With an updated schedule for the week we were ready to continue. Things finally began to cooldown again at the Testa Center.

After an intense and very interesting first day of the Testa Challenge we concluded that it’s always a lot of fun to work at the Testa Center. Even though it might not always go as planned and late nights in combination with early mornings are needed; this is how innovation is made and how we push the boundaries to make it happen.

Are you into technology in life science and bio-process, make sure to contact Testa Center to learn how you might accelerate your project together with us!

Day 2: Lights, Camera and Action - Upstream in bioreactor with cameras, sample analytics, in-bag sensors, parallel shake flask reactors and in-line mass spectrometry

Day two was when many of the participant’s experiments were going live; Video analysis detection, live process-data streaming from Sweden to the US, in-bag sensors to retrieve data from the bioreactor and in-parallel flask ShakeReactors replicating the bioprocess in small-scale. Everything went according to plan, until we had to reset and start it all over again.

It was an early start for those that took part in the inoculation step. The scene was set and now the Testa Center staff took stage to start the show. Firstly, the 50-liter Xcellerex Disposable Reactor and atSpiro’s ShakeReactors were synchronized. Starting both devices at the same time, with the same growth media and culture should make it easier to compare data and thereby the characteristics of the reactors as well.

Technology setup

Freesense were also set for today’s agenda, having added their sensors in the bag the day before. The small sensors will retrieve crucial data during the bioreactor run from inside the single-use bag to provide key insights into culture and bioreactor health. Using such data Niels Jensen and Christian Bülow can help us to optimize our next batch, scale-up processes, or further bioreaction development work.

After having set up the stage and lights, next are the cameras. Before the bioreactor was started Oskar Flordal and Samuel Eliasson Godonou from Unibap had set up their camera to capture videos of the bioreactor. Accompanied by analysis software, they will be able to detect when abnormalities occur in order to train as well as utilize machine learning processes.

Our participants from the US, Scitara, have also begun their set up procedure. Unfortunately, due to the pandemic they were unable to travel to Uppsala and having to participate remotely. Non the less with the flexibility which the Testa Center offers, we were able to set up a live feed of the lab for our remote participants and have regular video conference calls to ensure a smooth process which enabled us to integrate their data communication solution.

All good, until...

After some sampling and analysis on the spectrophotometer we all thought this will be a “challenge”-free day, until someone heard a dripping sound. A sound that any upstream specialist would recognize because they don’t want to hear it. The sound of a leaking bioreactor bag. Single-use bioreactor bags are designed to be robust, easy to use and efficient. Therefore, the occurrence for a bag to leak is very unlikely, and in this case also extremely unfortunate. Queue the action.

Fortunately, the extremely experienced Testa Center team were very fast to respond and handled the situation promptly. The culture was pumped into a new sterile bag and any leakage was cleaned up in order to allow continuation of the experiments. Like clockwork the application specialists immediately had a “problem-solving” meeting on how to proceed and how to set up a new bioprocessing run which all was executed within less than two hours. With a combined effort and a pool of knowledge from all the experts we managed to prepare everything for a new inoculation for day three of the Testa Challenge week. A true show of skills and exceptional support the Testa Center has to offer.

Learning in Testa Center

At the Testa Center you will learn a lot about your processes and experiments, but also about everything that you perhaps didn’t plan for. We strongly emphasize to do things together, to learn from one another, to build a network of people as well as competences and, importantly, how to reduce risks. We live by this mindset for any of our technology or bioprocess projects; do you feel the same? Then come and talk to us about your project.

Day 3: We will make it happen!

They call Wednesday a hump day for a reason. After day one and day two pushing the teams to their limits, the learning curve was certainly step. But at the Testa Center we keep on pushing, and things started to look more downhill.

Due to the unforeseen circumstances from day two, day three was committed to restarting the bioreactor and catching up the with the intended schedule. In the meantime, we started to evaluate and analyze atSpiro’s ShakeReactor run and assess the level of produced product and as well perform metabolite analytics from samples collected at hourly intervals. For this step we used Gyrolab’s xP workstation, Roche CEDEX Bio Analyzer and Cytiva’s ÄKTA Go systems. In parallel, also at hourly intervals, samples were taken from the 50-liter Xcellerex Disposable Reactor (XDR50) and preserved in order to be shipped to the UK, to be received by our second remote participant, IS-Instruments. IS-Instruments will be analyzing using state of the art deep-UV Raman technology and later compared with all the data retrieved in the Testa Center lab.

pH 9? No problem for the ArgusEye sensor!

During the analysis one of the four SkakeReactor results indicated an unexpectedly high pH, a pH of nine in fact. Charlotte Brink, Downstream Specialist from Testa Center, became very suspicious about it. Erik Martinsson, who’s been at Linköping university before starting ArgusEye said, with his always so calm voice:

“Just keep on going, we will make it happen!”.

Erik Martinsson, ArgusEye.

This is a type of mentality we welcome at the Testa Center as sometimes we need to roll up our sleeves and keep working on it until it’s right!

This is a type of mentality we welcome at the Testa Center as sometimes we need to roll up our sleeves and keep working on it until it’s right!

Not knowing what we might expect, we began further analysis using the ÄKTA pure 25. But this time it was modified to integrate ArgusEye’s in-line nanoplasmonic sensor into the flow path enabling an additional high-tech detection method. Erik’s years of experience paid off – the result was better than expected according to the UNICORN software analysis as well as data from ArgusEye’s system.

Sampling, analyzing and collecting the data

Later in the afternoon it was time to connect the ÄKTA pilot 600 and the ÄKTA Pure 25 to purify the samples by affinity chromatography utilizing the Capto L resin. Throughout this step of the biomanufacturing process Scitara’s DLX data platform was connected using the UNICORN OPC interfaces. Having the DLX data platform enabled with ÄKTA instrument UNICORN control-system data, as well as most other instruments used, enabled us to create nice code snippets, publishing results directly into live data sheets, trigger custom web-application code, much more.

Later in the afternoon it was time to connect the ÄKTA pilot 600 and the ÄKTA Pure 25 to purify the samples by affinity chromatography utilizing the Capto L resin. Throughout this step of the biomanufacturing process Scitara’s DLX data platform was connected using the UNICORN OPC interfaces. Having the DLX data platform enabled with ÄKTA instrument UNICORN control-system data, as well as most other instruments used, enabled us to create nice code snippets, publishing results directly into live data sheets, trigger custom web-application code, much more.

An positive attitude throughout the process

Certainly, one memorable feature that kept everyone going was the positive attitude throughout the process. After the incident of the bioreactor bag from day two, we kept the momentum going not only by cleaning and preparing the bioreactor for another run, but also stepping it up even further when Jozsef Vasi happily volunteered to come in exceptionally early on day three to start the next batch. His determination and the use of the single-use bioreactor (XDR50) made all the difference in the world right there. Jozsef was a hero to everyone that day in the Testa Center as this meant we could continue our Testa Challenge journey further into day four!

Do you also have people like that in your team? We think that you do! The circumstances in the Testa Center tends to show you that these people are all around you, given that you give them a chance. At the Testa Center we have a range of talented personnel ready to help you and your team to excel in your next project. Come and meet the team to learn more!

Day 4: Strategies on how to be successful in biopharma

Biopharma trends in 2020 are;

1. The development of novel personalized therapies.
2. The ever increasing costs for the next generation of biologics.
3. New technology in biopharma benefits the process development, quality by design and standardization.
4. Companies are adapting to “fail fast and fail cheap”-methods be become more efficient.

Given these trends, can you please describe your product-market-fit? -A question that all participants, in one way or another, had to answer to during the Testa Challenge.

Deep-dive into innovation in biopharma trends and strategies

Day four was in addition to day one, two and three, an intensive day. As a further aim for the Testa Challenge week, we had invited several guest speakers  (due to the pandemic only virtually) to talk about various topics ranging from “Bioprocessing market trends: Addressing the challenges in the analytical and regulatory interface for novel biologics” to “The industrial perspective on innovation and startups” in order to is to really connect startups with industry.

After each of the the presentations we opened the floor for questions. The discussions that arose  during these meetings quickly became a unique opportunity to ask those key questions to help the startups put themselves ahead of competition, as well as better understand their value within the current and future market.

Meeting industry and experts

Mixing industry and startups is a key element in the Testa Challenge. Meetings and discussions have been carefully set up between the participating companies, and industry representatives. The Testa Center functioned as  an open arena for investigating the innovations of the startups with clear preconditions regarding their intellectual property rights, without the risk for loss of confidential information.

As the Testa Center is based on the Cytiva company grounds, we were able to further strengthen the interactions between the participating companies and industrial experts. Leveraging the ideal location of the Testa Center, the six startups were able to have individual “focus meetings” with principle scientists and possible future users of their products.

Listening and learning from previous expert experiences meant that participants could re-evaluate their product if needed in order to not avoid “reinventing the wheel” or perhaps certain pitfalls. Additionally, it provided a platform to future-proof their products by understanding what the current and future demands in the industry are. In some cases, the discussions lead to a collaborative approach to solve common obstacles both parties were facing from different angles.

Meeting potential future users

When meeting potential future users lighting started to strike. Learning from senior application specialists what are prioritized product features was said to be something very valuable for many of the participants.

 “The discussions we had, and contacts we made today might be as valuable, or even more valuable, as the lab experiment.” Was one of the final remarks from Erik Martinsson, CEO of ArgusEye, as we closed the doors for the night.

Together we accelerate industrialization

The day really symbolized what we do in the Testa Center. The method of mixing industrial expertise, senior application specialist with entrepreneurs and academic spinouts is one of our core concepts which we also wanted to incorporate into the Testa Challenge. With less than a week into the Challenge we already see a magnitude of great outcomes  where companies were able to accelerate their projects during the intense few days working with the Testa Center.

Do you think this sounds interesting, we are continuously looking for new projects and are open to give you an introduction with short notice. Send us a message today to get introduced!