August 23, 2018
BioProcess Insider brings the news as it breaks. At the BPI Theater @ BIO, editor Dan Stanton conducted a series of interviews live on stage to report on the latest movements in the biomanufacturing industry to start each busy day of dealmaking in Boston. Below we summarize and share the videos from his DAY TWO conversations with a number of biopharmaceutical executives on Wednesday 6 June 2018.
Jacobs offers a range of services — including advanced planning and programming, design, construction, commissioning, qualification, and validation — and has been involved in a number of large biomanufacturing facility projects. “We’re seeing now a tale of two facilities in some ways,” Sommer began, “the need for capacity in traditional stainless steel manufacturing facilities to pump out as much product as possible and the need for disposable facilities with quick product turnover and high flexibility.”
Having begun in the early 1990s, Jacobs benefits from a business model that expands capabilities through acquisitions that bring in subject-matter expertise. The firm serves three end markets (life sciences, electronics, and specialized manufacturing), incorporating learnings from one industry that might be farther along in certain capabilities into others. Sommer said that biomanufacturers need more advanced ways of harnessing data, leveraging information from the engineering cycle of a project through its construction, commissioning, and validation.
Jacobs pays close attention to technological advances in the highly regulated biotechnology field. Sommer highlighted the benefit of meeting with the FDA to review criteria for facility design for new product modalities. Asked to comment on what disruptive technologies clients are installing in their own facilities, he pointed to innovations in continuous chromatography. But he is seeing a slow progress toward continuous processing as the industry balances capacity needs with needs for flexibility.
“The biggest challenge we have is talent retention,” he concluded. “We’re recruiting at the best universities, making sure that people are going into engineering.”
Mab-Venture was established in 2014 and raised US$5 million in private equity in 2016. The company has a research-and-development and pilot-production facility in Shanghai, China. In 2017 it built an additional 3,350 m2 of pilot-production space to support biologics development and manufacture.
Wang commented on China’s changing environment for biologics development and manufacturing. He was among the first wave of people returning to China after years of experience in the United States developing expertise in setting up laboratories and manufacturing sites for biosimilar development and biologics. Mab-Venture was launched to bring operational and product-development expertise to support the growth of the Chinese biopharmaceutical industry.
He discussed the ongoing process toward harmonizing Chinese regulations with international standards, which will shorten time lags for approvals in that country. He also spoke about how China is encouraging growth of a domestic market through participation in manufacturing reforms. Although much of China’s own biopharmaceutical products are still in the R&D pipeline, the country’s industry realizes that substantial manufacturing capacity will be needed. In partnership with Thermo Fisher, Mab-Venture’s smart factory will be the first “smart factory” in the Asia–Pacific region. Its initial design will accommodate multiple 2,000-L bioreactors handling up to 10,000 L in total capacity.
Wang agreed that beginning with smart-factory approaches rather than stainless-steel designs is speeding the generation of a biomanufacturing environment in China, with heavy investments currently from consortiums, construction firms, and suppliers. He thinks that by drawing from recent industry advancements in smaller footprint processing, China is being exceptionally innovative in planning for the facilities of the future.
The Pfenex Expression Technology platform is a system based on Pseudomonas fluorescens bacteria, which was used by the Dow Chemical Company for years to make large-scale industrial enzymes. In 2001, a team assessed that technology and realized that it would be a great production platform for therapeutics and vaccines. They spent the next five years researching and building the platform. In 2009, Pfenex Inc. was spun out of Dow, and it made an initial public offering in 2015.
Pfenex sequenced the genome of the organism and now is able to mine that genome to find genes either to delete or overexpress. The P. fluorescens genome has genes coding for 90 proteases. We have coded each one of those and banked the host-strain phenotypes. In parallel with that, we have looked for plasmid components, such as ribosome binding sites, isolated and characterized those, and built what we call rapid cloning vectors.
We can combine 20–30 plasmids with one of 200 host strains and rapidly create a broad range of expression hosts. Using high-throughput robotics, we can evaluate 1,000 strains in triplicate (3,000 microfermentations) and within a matter of weeks identify an optimal production strain. This is especially useful when working with engineered proteins that can be harder to produce. Microbial fermentation is faster than mammalian cell culture: 36 hours rather than 14–17 days. The Pfenex platform’s production strains will provide a large amount of high-quality protein per unit volume in a short time. Getting a robust production strain that can be used to support clinical and commercial manufacturing rapidly has a positive influence on cost of goods over a product’s lifecycle.
Comparing the Pfenex platform with an Escherichia coli platform, we see improved expression. However, not all of our products are expressed in double-digit grams per liter. Although we have higher titers, this platform also makes soluble protein. One of the biggest challenges working with microbially expressed proteins can be the need to refold them, with the associated people and infrastructure. Eliminating that need allows a company to manufacture in a smaller facility footprint.
Pfenex has developed in three different phases: first as a technology and service provider supplying gene expression and process development and licensing our technology to drug developers; then using the service business to generate revenue for its own product development. Now we are developing a pipeline of our own and seeking codevelopment relationships.
Jornitz began with an overview of his company’s prefabricated cleanroom offerings. The company prefabricates cleanroom offsite at its facility — either a single cleanroom or an entire cleanroom “cluster.” G-Con conducts the factory acceptance test (FAT) onsite at its Texas facility, from which it ships the modules to buyers. Parts can be installed at a client site within two days, then interconnected and included in the client’s FAT. The modular nature of these units allows some clients to use such infrastructures at different locations — e.g., for cross development — or repurpose them entirely.
Jornitz noted that modular is a very generic term for a multitude of different construction approaches and different scenarios. G-Con differentiates its offerings by referring to them as “podular services and instances.” Clients need their own technologies designed into the cleanroom pods so that the resulting pods can be integrated into a facility without interrupting existing processes.
Examples of current requests include delivering single-use bioprocess systems at different scales. The “podular” system serves the needs of cell and gene therapy developers by enabling them to scale out multiple different blocks. G-Con also is working on incorporating a continuous manufacturing platform into its designs. As companies are able to shrink their bioreactor systems through single-use and increased titers, he believes that “pods become much more amenable to that particular process.”
His company’s customers include contract manufacturing organizations (CMOs) that need to provide cleanroom infrastructure with robust containment levels for multiple clients. With increased regulatory stringency focusong on design of compounding pharmacies, pods can be preinstalled and prequalified for those uses as well. G-Con works together with regulators who actively train in new technologies. The company also seeks to help lower prices of installation by creating turnkey facilities that can be copied and cloned.
A recent bioprocess site installation for Just Biotherapeutics in China was installed and qualified under budget to accommodate the company’s needs. Jornitz said that China is the number-one growing market for biopharmaceutical facility contruction, although his company is extending its services into Europe as well. It has recently signed a manufacturing agreement for a new site in Ireland.
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