CRB’s newly released biopharma market outlook: Horizons: Life Sciences, is fueled by survey insights from more than 500 pharma representatives on key issues facing their organizations.
“The report is looking at all the different disruptions within the life science industry over the past 12 months, with an emphasis on mRNA and warp speed delivery, as well as other emerging trends,” said Noel Maestre, CRB’s vice president of life sciences.
Of note as well, he said, was the level of financial investment in life sciences during 2021 - it was at a record high, and that should yield a positive outlook for at least the next few years.
RNA-based technology as disruptor
One quarter of the respondents to the CRB survey said they are pursuing or plan to pursue RNA therapies across a wide array of indications, from autoimmune diseases to oncology.
The publication also finds the field of oligonucleotides, which differ from mRNA therapeutics in terms of the diseases they treat and the way they are manufactured, will rapidly transform in the near future.
“mRNA is here to stay. It has come on the scene and has become a proven technology because of a global pandemic. Our clients are now targeting over a dozen different indications based on RNA technology. We fully expect to see a massive surge of predominantly mRNA but also other RNA technologies some two years plus out and they have the potential to displace or completely replace some of the traditional biotech modalities like therapeutic proteins,” Maestre told us.
The simplicity of the manufacturing facility required is also what makes RNA-based technology so ‘elegant’ and appealing, he said.
The facility-type disruption caused by the technology is partly due to its detachment from large-batch cell culture; there is simply no need for a huge facility with huge bioreactors and the associated downstream equipment. Instead, manufacturers can produce their required amounts in modular, rapidly built, local facilities.
Those manufacturing attributes mean that companies can make RNA drugs close to the patients who need them, and in emerging markets, which would simplify shipping logistics and improve access. The efficiency and commodity of scale of this model have already been proven. It is now just a matter of stamping out a copy to deploy it, even in areas where there is no other current pharmaceutical manufacturing going on, according to the CRB team.
“The industry was already going in that direction, but mRNA technology has helped amplify the focus on modularization,” said Maestre.
Cell and gene therapy trends
Analyzing trends in the cell and gene therapy manufacturing sector, he said a significant number of CRB’s clients in that arena are looking to move away from patient specific, autologous cell therapies to more allogeneic or stem cell based therapies.
“We have always assumed that might happen because of the logistical challenges of doing patient specific cell therapy - every patient requires its own independent batch, and the starting material is usually harvested from a patient who has already had an illness - that is not a very advantageous way to start off a GMP manufacturing process - there is a lot of variability in the starting material.
“Also, it is impossible to scale up autologous cell process, they have to be scaled out because every piece of equipment is dedicated to a single patient.
“So there is a huge driver from a manufacturing and a GMP raw materials standpoint to move away from patient specific.
"We are now seeing a pretty clear shift in that direction, at least based on the client data.”
There is a lot of promise with off-the-shelf, cell therapy approaches, but many hurdles still need to be overcome in that space, not least years of data to prove their efficacy: “I am fairly confident, though, that if the entire industry is starting to move in that direction, it is probably not 10 to 15 years out, we should be able to get there in the next five to 10 years,” said Maestre.
That is not to say that autologous therapies are history, finds the report. Closed, automated, single equipment platforms are also emerging as a promising alternative to high-cost and inefficient open processing in this arena, it highlighted.
Process-in-a-box systems could eliminate the cleanroom altogether. For those with autologous cell therapies in their pipeline, this is game-changing, finds the CRB experts.
Manufacturers could scale out by densely stacking large volumes of these closed and automated systems inside a warehouse, while reducing labor costs and continuing to focus on small, individualized product batches, they continued.
Process-in-a-box systems could also revolutionize allogeneic cell therapy manufacturing, solving many operational complexities, argued the team.
“There is strong desire to go from where we are today, which is still very manual, to that fully automated, fully closed process and the pioneers that are going to be able to make it work can really capitalize on it,” said Maestre.
Many contract development and manufacturing organizations (CDMOs) are already pushing hard to drive the factory-in-a-box concept, with the realization that greater capacity and faster throughput will mean more clients in the long run.
“Lonza has its Cocoon [platform], which is partially factory-in-a-box. Miltenyi Biotec, a German company, has probably the closest thing today to what we call an end to end process [system]. Although the challenge here is that, every client’s manufacturing process varies greatly so, until there is more [industry] standardization, most companies are not able to use it as an end-to-end processing tool.”
In terms of genetically modified autologous cell therapy technologies - viral vector, cleavage enzymes or RNA based systems - the report finds viral vector manufacturing is the most established and well-understood, but it is difficult to scale because of transfection challenges and issues related to containment and segregation.
Leveraging technology synergies
Developers, according to the report, should focus on a single technology to fuel their whole product pipeline, instead of “using an mRNA platform for cell therapy over here and viral vectors for vaccine research over there.”
By building technological synergies into their manufacturing strategies, companies can leverage the same talent pool, facility layout, equipment platforms, supply chain inputs, and other resources for as many products as possible, they stressed.
With increasingly complex pipelines comprising multiple modalities, there is a drive on as well to decouple the process from the facility design, to have manufacturing spaces that are modality agnostic, so that facilities have the flexibility and adaptability to be able to campaign through an entire pipeline of different products as opposed to relying on building very specified manufacturing suites.
Supply chain shortages
Meanwhile, vulnerabilities in the pharmaceutical supply chain were “very real” throughout the pandemic, and there are ongoing holdups, said the life sciences specialist.
“We are seeing supply chains shortages for raw materials, critical components, and disposables. Process equipment is at a record high in terms of lead times these days – equipment like fill lines to fill vaccines or vials are over two years out at this point. This is placing a massive strain on the entire industry."
The rapid rate of growth the industry has seen over the past 18 months was behind the supply challenges.
“The drive for critical speed to market has created some fairly inefficient processes, which will surely be optimized over the next decade.”
Pharma 4.0
Looking to developments such as artificial intelligence, algorithms, machine learning and digitalization, Maestre said these tools are going to revolutionize manufacturing in the coming years and the pharma industry is advancing rapidly in this respect; it is seeking to implement many of these technologies.
“Predictive maintenance is starting to become commonplace in all the newer facilities. We heard, via the survey results, that many companies are looking to up their level of digitalization over the next one to two years. That is probably a bit optimistic. The technology is there but it is still very nascent. The adoption period is going to be a little bit slower than what people are anticipating but I fully believe that, within two to five years, almost every new facility is going have some degree of digitalization built in.”