Innovating in Bioprocessing at BPI Europe
Chart Biotechnology attended the BPI conference in Amsterdam 9-12/May. The program for these conferences is so comprehensive and there are several parallel sessions, so one needs to focus, otherwise we spread ourselves too thin. In our case, we had a theme – Innovation in bioproduction – reflected in our poster “How will biotherapeutics be produced in 2063?”.
As our selected talks were peppered through the 5 conference streams and that was on top of wanting to check the novelties from the many exhibitors, these were busy days!
A good thing is that the registration also includes access to the conference recordings, so we can check later for any lost details.
In addition to the conventional process themes such as cell line and process engineering and gene and cell therapies, BPI added two important ones: bioprocess sustainability and industry diversity, inclusion, and equity initiatives.
I really like how BPI outlined sustainability on the conference screens, with a summary of the talks and initiatives taken onsite – and including good advice for sustained healthy participation of the delegates too (hydrate, move, get fresh air, participate in the conference run…). Loved to see this!
Yes, only a small number of presentations were related to sustainability, but it is a good initiative nonetheless, and a good way to raise awareness to the themes.
Next door to this conference, a plastic recycling meeting was taking place. It is important that the Bioproduction community takes these themes seriously as well. We wrote a blog earlier this year about sustainability initiatives in bioproduction.
Regarding the sustainability of the event, I’m interested in seeing some numbers.
We had paper plates and cutlery, meat-less offers on the menu, and digital agendas. I did not see the small mountains of plastic waste that used to appear at these events after every refreshment break.
Personally, I’d like to know the volume of food waste and trash generated by this conference, compared to e.g. the BPI conference in 2018, and how much of the trash generated this year was destined for reuse or recycling.
On Diversity, Equity, Inclusion:
Again, kudos to BPI for organizing a “Product Stage” participative workshop about this theme. The conditions for the workshop, on the floor of the exhibition hall, were not the best, but what is important is that it was taking place, and many chairs were taken. One delegate noted, looking around the floor at the mainly European ancestry attendees, that the industry does not seem to be doing a great job about inclusion nor diversity. That is unfortunately correct. Further, the imbalance in men/women presenting at the whole conference was strong. This should be a concern, because the initiatives that attract women and diverse ethnic backgrounds to training in Biotechnological Engineering seem to not deliver the conditions that allow them to progress and be ready to participate in these conferences. We are all poorer for that, as we know.
Continuing to raise awareness of these imbalances is important, to understand what changes continue to be needed to improve the status.
On Future thinking and Innovation – Global Health
Mitigating the striking global inequities in access to SARS-Cov2 vaccines is requiring innovative thinking from all in the industry ecosystem. A recent WHO map of global COVID vaccination rates shows how in vast areas of e.g. Africa the rate of vaccination is still only 40%, half of what we have in Europe, for example, or in parts of South America. PATH, Medicines Patent Pool (MPP) and WHO presented their initiatives to generate momentum in creating capability as well as manufacturing capacity in low and medium income countries (LMIC). The NGOs working to build capacity locally are fully aware of the criticality of involving local authorities in their programs to achieve sustainable results.
PATH’s initiative “Sustaining vaccine manufacturers” is a program to provide technical assistance to LMIC manufacturers of high value high impact vaccines, with several focus areas such as national licensing, readiness of supply, continuity/capacity increase, vaccine platforms, amongst others. In the presentation by the PATH Head of the CMC team, I noticed that, instead of general statements about goals and ambitions, there was a level of concrete information that makes it close to reality, which is a very nice evolution to observe. The portfolio of indications in this project includes enteric and diarrheal diseases, respiratory and maternal immunization, zoonic, emerging and sexually transmitted diseases and combination vaccines. The PATH team mapped the current African manufacturing capability, to find that it is mostly focused on fill-finish of COVID vaccines, clustered in North and S Africa, and the capacity committed exceeded 500 million doses. PATH has worked with the countries in Africa, to make projections about the 2040 annual expected vaccine demand volumes, compared with 2020 demand. Covering legacy vaccines, expansion of HPV, Pneumococcus, Rotavirus, covid19, malaria, HIV and outbreaks (inc ebola, influenza, chikungunya and Disease X), the expected demand is two thousand and two hundred million doses, which greatly exceeds the continent’s current manufacturing capacity.
Furthermore, some of the existing facilities are not equipped to manufacture viral vaccines, the techniques used may be quite old (vaccines in eggs), the facilities are mainly state owned or non-profit, and there is a lack of skilled working force. Further challenges are related to the supply chain and to the lack of maturity of regulatory authorities. New facilities and some infrastructure could rely on capital investment by development banks, but running costs are also very important to keep in consideration. This is the type of clear local information that is needed to inform program implementation. We look forward to continuing to follow the outcomes of PATH’s initiatives.
The MPP and WHO are partners in a “mRNA transfer initiative”. This initiative uses a multilateral technology transfer model, with the various stakeholders participating to establish and validate the technology, which can then be used for locally developed and produced vaccines. Their road map has 4 main packages, constituting a staggered technology transfer approach.
Advancing Product Preparedness
As we all observed, and many of us benefitted from them, the COVID pandemic allowed for product development in record times and led to many innovations in bioproduction and to very close dialogue between manufacturers and the regulatory agencies, who were keen on expediting potential solutions for the pandemic, while keeping the usual high safety standards. Presentations from companies that engaged in those interactions were enlightening.
One of the important themes highlighted was how to keep using the innovations that worked in the pandemic, including regulatory innovations, so we “don’t go back to taking 10 years to develop a new vaccine” as the speaker from Moderna put it. These innovations led to shorter product development times and also contribute to global preparedness for future infectious agents. He spoke about “A mature technology requiring adapted regulatory oversight – science and risk-based regulatory decisions”.
This and other speakers presented how the “platform” concept was used in CMC discussions with the regulatory agencies. Prior extensive characterization of process steps, such as stable bulk CHO culture, as the speaker from Lilly described in his presentation, allowed them to cut months in development of bamlanivimab, through what he called “the power of the platform”. Another example of this “power” is to consider mRNA critical quality attributes that are disease agnostic, thus allowing for regulatory aspects to be clarified independently of the target indication.
An essential link in the preparedness chain is the need to coordinate supply chains and how best to create resilient supplier networks. This was the subject of an excellent presentation by Prashant Yadav (INSEAD). He discussed supply network “density” and identified IP and regulatory as some of the hurdles to overcome in building an effective system. Using mRNA manufacturing as example, it is clear there are many uncertainties, such as limited visibility into overall demand of reagents and key inputs, few GMP suppliers and unclear guidance on how to switch suppliers. He proposed that supply networks need to change from bowtie (constrained transfer to from early phase to manufacturing scale up teams) to diamond (strong interfacing between suppliers and the commercial scale up manufacturing teams) shape and discussed the possible support of public agencies in improving the supply network resilience.
More about the Future – data, automation, machine learning, AI and also Biology
As expected, the main body of the Conference covered the progress made developing the most standard bioprocessing tools and biology. Hearing the emphasis that data scientists put on the importance of good communication and silo breaking was for me a very pleasant surprise (though maybe this just shows my own ignorance). A culture change is needed, they said, and everybody (not just the modelers or data scientists) needs to be involved and understand the broader needs, objectives and impact of the projects. Datanow highlighted the importance of considering knowledge transfer and of capturing it in the models.
They are combining process engineering knowledge with machine learning, with the eventual goal of achieving automatic transfer of knowledge between products and scales, direct learning and continuous model refinement from process data, i.e., the future system will automatically learn from new data, with no need of prior knowledge, adapts to new knowledge and improves decision taking.
Synthetic biology is continuing to impact Bioproduction – as the industry continues to use E.coli as one of its work horses, the potential for using it to make mRNA is being explored. Syngensys spoke about “Expanding the manufacturing solution for mRNA production”, through sequence engineering (i.e., the various components of the mRNA and also the genetic components that impact on mRNA production) and manufacturing solution engineering.
So, “How will biotherapeutics be produced in 2063?”
The first approved recombinant biotherapeutic was made in E.coli, and approved just over 40 years ago, so, can we tell how we will be making biotherapeutics in 40 years’ time?
While the new technologies – cell therapies, gene therapies and RNA-based therapies – have reached market approval in recent years, after long roller-coaster periods involving many setbacks, and have had a huge impact on public health, they all come with significant disadvantages related to their cost of production and to the complexity of the processes used to make them. At this conference, we heard how process data collection is improving, to allow for development of models for machine learning and for developing AI that will contribute to process intensification and faster process development, even process knowledge applicable for new products. These activities are for now focusing on the most established bioproduction systems, in particular the mammalian CHO system.
One way we like to think about the production of biologics in the future, is to envision the “ideal” system. “Ideally”, medicines are safe and efficacious, personalized, made in environmentally responsible ways, that do not lead to accumulation of harmful waste (including harm from unused medicines), they can be made mobile for space travel and space exploration, and they can be deployed rapidly to challenging places here on Earth, where they may be needed. So far we have developed bioprocesses that deliver life-saving medicines and vaccines, but production capability is not at the moment equitable, and much more needs to be done in terms of sustainability. Developing new technologies takes a long time, and adapting the current processes may not deliver our “ideal” production system, so we need to be brave, take risks and keep an open mind for new technologies, if we are to deliver step changes in bioproduction.
Synthetic biology is already making a mark on bioproduction processes, and I believe this is just the start (we’ll be following with attention, for example, the partnership between Ginkgo Bioworks and Sensible Biotechnologies on mRNA manufacturing). In future bioproduction conferences we expect to hear much more about outcomes from the current synthetic biology applications and all the technologies that support them, about the new AI applications and perhaps something more about microfluidics.