Throughout history, medical paradigms have evolved in large, discrete steps, from superstition to herbal remedies, to redesigned botanicals, then small-molecule drugs, and initially, in the age of biologics, to therapeutic proteins. Each stage uncovered a huge gap in our understanding of the complex causality of health and disease, but provided the impetus–and opportunity–to bridge those knowledge chasms.

And so it is with what are currently known as “advanced therapies” — gene and cell-based treatments. The biopharmaceutical industry has spent much of the past, even as it devotes much of the present, to eliminating potential health problems arising from the manufacture of their products — mostly proteins — in living cells. That cells (to varying degrees) have become the product itself represents what may be the last great paradigm shift in therapeutics.


What does this mean in terms of the readiness, willingness, and even the feasibility of adopting Biopharma 4.0 ideas?

Industry 1.0 — the industrial revolution — was characterized by the replacement of humans by machines for manual work. Industry 2.0 involved processes and automation, followed by the current paradigm, 4.0, which is about capturing and managing information for decision making, extreme automation, and real-time monitoring.

On the basis of that evolution, Javier Aranguren, director of operations at VIVEbiotech, believes Biopharma 4.0 and advanced therapies are a natural fit.

“All implantable solutions in Industry 4.0 are applicable to gene therapy companies. Knowing the data, its trends in real time and, above all, the effect they have on the final product, is the challenge our sector will address in the years to come. This includes the Internet of Things, sensorics, artificial vision, statistics (Six Sigma), Scada/MESH software… all of which interrelate the data collected in real time in manufacturing and analytics. This should govern the decision-making of the company in the medium term. Data for data’s sake, without a deep analysis, doesn´t work.”

Fair enough, but by common definition Biopharma 4.0 encompasses a lot of new technologies and approaches. GEN asked Aranguren if some aspects of 4.0 might be more (or less) accessible to certain companies, and about the possibility of adopting number of components of 4.0 but not others.

“Most biopharma equipment already allows data capture in real time. This is a clear advantage over other sectors. However, the correct selection of the key parameters by the quality and production departments is essential, which will allow for much easier and valuable analysis. Deep knowledge, which always is given by people, is the only thing that allows the correct choice of key variables of the process that will give important results in the short term.” The objective is not to attempt to monitor every parameter deeply, but to “select and correlate the critical ones that are those that really impact on the product.”

The argument that 4.0 will, in addition to costing billions and diverting attention from discovering, developing, and producing treatments, has been made before (think: PAT, QbD), and as everyone knows protein-based manufacturing has not fully adopted those approaches.

This time is different, says Aranguren, because the “entire cell/gene therapy industry is taking steps in this direction. The advanced therapy products are very sophisticated and cutting-edge, and this young sector could clearly benefit from the advantages that Biopharma 4.0 confers. But we must go through the different stages that must naturally precede Biopharma 4.0 to have a robust implementation of it as soon as possible. We believe Biopharma 4.0 can ultimately help us overcome the main barriers to commercializing advanced therapies: cost-effectiveness, scalability, and safety, all of which directly benefits end users: the patients.”