Notes about bio-production innovators
From my experience working within bio-production, I observed some challenges faced by innovators in bioproduction.
Dan Stanton in BioProcess International, May 2018, refers to the pillars of technological advancement for Industry 4:0, amongst them: big data and analytics, process simulations, the industrial internet of things, cybersecurity, the cloud, additive manufacturing. In the same article J.Thommes – Snr VP pharmaceutical sciences and technology at Visterra Inc is cited: “We’re a data-rich environment, but we don’t quite use it like a grown-up industry would”
Within Biomanufacturing of therapeutics, manufacturing costs are not the main price contributor, but still, there is room for efficiency and pressure to find ways to gain it.
Upstream challenges: is CHO really the best technology for MAb expression? how slow and hard it seems, to get approval for products made with novel expression systems – vaccines has been carving a way, but they are not the norm – and development time for a vaccine made with a novel platform is considerable. And what about production optimisation? Evolution is happening when microorganisms produce in large scale, resulting in genetic heterogeneity – how to study it, predict it – and act on it effectively, if in the current most common gate staged strain development funnels do not predict “feedback loops”, to allow for strain genetic re-engineering, as the whole chain of development is unidirectional. Media and process parameters manipulation may not deliver the solution for genetic heterogeneity.
Downstream challenges: disruptive innovation, in particular for MAbs downstream processing has been slow to come to market. Protein A chromatography dominates. Using what is already known – even if costly – seems better than risking using something new, that may generate quality and regulatory challenges whose price cannot be calculated in advance.
Some, decide to go “all out”. Pfenex has, as an independent company, been carving a niche for its industrial P. fluorescens within biosimilars, since 2009. More recently Dyadic International made moves to expand use of its Myceliophtora thermophila. Emalfarb, the CEO of Dyadic, hopes to use this work horse of industry, for pharmaceutical applications. Biogen has also been for a few years looking for production systems that are alternatives to CHO.
What about the investment landscape? It has been hard for the innovators to devise compelling business cases in such a challenging environment, characterised by resistance to change where regulatory risk is perceived, and long product development times.
Single use bioreactors, a disruptive technology, responded to an industry call. This shows it is possible to introduce innovation to this industry.
Being optimistic by nature, I hope that the application of frameworks such as Quality by Design and advances in process analytics technology, other improved methods and technologies to monitor and measure production parameters and further discoveries about the biology of the production organism and of the products’ chemical biology, will generate a better understanding of the risks being introduced by innovation. A better understanding of risk will hopefully inspire and inform regulatory frameworks that will be met by a range of improvements and radical solutions to current efficiency bottlenecks in the field. With that clearer risk path, a fresh interest from investors may come to meet those innovators.