The Roundtable Discussion at RXIX

The Roundtable

In keeping with the conference aims of fostering and supporting knowledge sharing, discussion and networking, RXIX will host a new “Yield Roundtable" session.

Roundtable Goals

The Yield Roundtable will give participants a chance to ‘dig a little deeper’ into areas they are passionate about, as well as build and strengthen connections with like-minded conferees. Using engaging, open-ended topics, conferees will share their experiences, brainstorm questions, yield new ideas and have conversations in a very different way to oral or poster sessions.

Roundtable Format

There will be four simultaneous Yield topics discussed in separate meeting rooms. The topics, including the general themes and key questions, are curated by the Yield co-chairs. We will invite participants to be to act as table moderators and facilitate the discussion. They will help determine the themes or questions that are specifically relevant for the participants at their tables, ensuring a lively flow of ideas and paying attention to the overall outcome of the discussion.

Roundtable Topics

Assessing Protein Manufacturability

Chairs: Michelle Butler (Roche), Richard Willson (U. Houston)
While more traditional protein therapeutics continue to dominate the field, we’re also experiencing the exciting emergence and evolution of other therapeutic formats (bispecifics, tetravalent mAbs, antibody-drug conjugates, enzymes, peptides, etc.) that offer unique treatment options for patients. These novel formats (as well as emergency-use and ton-scale products) pose new challenges in manufacturability assessment, process efficiency and in designing scalable manufacturing processes that fit product, economic, organizational, and regulatory requirements. In this session we will have an open dialogue on experiences, insights and ideas into developability assessment and manufacturing strategies for traditional biotherapeutics and emerging formats.

1. What are the pitfalls (or challenges) and successes in assessing developability and designing a process especially when there is no large accumulated dataset of relevant prior experience?
2. How and where can we best use HTS (High-Throughput Screening), mechanistic modeling, in silico prediction or other methods to predict manufacturability and speed development?
3. How have existing purification and analytical technologies been leveraged and what new technologies are needed for the future?
4. What manufacturing, supply chain and drug product issues are posed by novel formats or very high mass demand products (ton/year) and how can these be overcome?

Continuous Processing: Opportunities and Challenges

Chairs: Kevin Brower (Sanofi), Alois Jungbauer (BOKU)
Looking to the PAST, it has now been over a decade since technology development in continuous manufacturing began its emergence. Progress has been achieved despite technical hurdles, historical headwinds, and occasional skepticism. Nonetheless, the PRESENT setting is one where implementation of integrated and connected or continuous processes has been realized (or soon will be) across much of industry, buttressed by invaluable contributions by academia, vendors, and industry alike. Therefore, we propose to use this Workshop to look to the FUTURE, leveraging the expertise of our Recovery community to further the disruptive potential of continuous processing to transform patient access, enable real-time release, and support sustainability efforts across the industry.

1. In interconnected unit operations we have propagation of disturbances and fluctuations of mass flow. How do we determine when, and how, to divert material or to shut down the system? Where/how does PAT play a role?
2. Many of the separation technologies (resin, filters, membranes) of the present have been designed for high flux, short duration operation. How might we envision technologies for continuous manufacturing processes of the future?
3. Was the institutional hesitance to support continuous processes a mindset limitation or a reflection of technological immaturity? What can we learn from our collective experiences overcoming organizational resistance towards new technological approaches?
4. What opportunities / limitations does integrated continuous biomanufacturing afford related to Sustainability? Are there unique opportunities for continuous manufacturing related to single-use waste, water utilization, or other key environmental metrics?

Overcoming Scale-up and Yield Constraints in Gene Therapy Manufacture

Chairs: Susan D'Costa (Alcyone), Andrew Tustian (Regeneron), John Pieracci (Biogen)
Advances in the productivity and scale-up process of viral vectors for gene therapy are critical to expanding gene therapy products beyond the modest patient populations of rare diseases. Continual improvements in productivity are driven through high cell density processes and new production systems. These improvements in the upstream process put considerable pressure on downstream processes to produce high quality, low residual product with high process yields and low costs of manufacturing. In this workshop, we will discuss translating best practices from established biologics production to the manufacture of viral vector products for gene therapy.

1. What critical lessons learnt from the scale up of mAb downstream processes can be applied to viral vectors?
2. How can viral vector producer companies partner with the service industry to ensure applicability, diversity, and standardization of process and consumables?
3. Are chromatographic solutions sufficient for enrichment of full particles (AAV)?
4. Are there aspects of building a mAbs platform that could have been streamlined through better collaboration or information sharing between companies that folks in Gene Therapy improve upon? Any suggestions on how to make this successful?

Manufacturability for Pandemic Preparedness

Chairs: Andrea Rayat (UCL), Gisela Ferreira (AstraZeneca), Brian Kelley (Vir Biotechnology)
In this workshop, we will build on the oral session “A Call to Arms: Biotechnology’s Approach to Address Pandemics” and discuss opportunities for accelerating the approach to first-in-human clinical trials as well as commercializing biological products. For well-established and highly characterized products like monoclonal antibodies the landscape has changed since 2020 as multiple companies brought several mAbs to millions of patients across the globe in a timeframe that was unparalleled. The industry can now build on the success of new modalities such as mRNA and adenovirus vaccines to accelerate other programs in this space, which is an expansion of unprecedented scope.

1. What practices and innovations can we keep beyond the pandemic that will accelerate future drug development (e.g., impact of pandemic therapies on non-pandemic targets, others)?
2. What were the benefits of existing activities on non-pandemic targets which were then evolved to deliver pandemic therapies?
3. How should we prepare for future pandemics as an industry?
4. Considering process platforms for mAbs and other modalities, what was leveraged and could be used in the future (including lessons from a regulatory standpoint)? To what degree are viral vectors and mRNA platforms already established?