All Eyes on Biopharma Trends

The Medicine Maker and Ireland’s National Institute for Bioprocessing Research and Training (NIBRT) have collaborated on numerous occasions – perhaps you recall our cover feature from 2016 (here). More recently, The Medicine Maker and NIBRT teamed up to learn more about current manufacturing practices and trends in the biopharma industry, and where the field is heading next, by conducting a survey of industry professionals. You can download the full survey report – for free – here (1).

Our goal? To help inform – dare we say, advance – the biopharma industry by looking at current issues, incoming trends, and exciting innovations. In the next few issues of The Medicine Maker, we’ll be sharing what we’ve learned from the survey, and what some of the esteemed members of our 2018 Power List have to say about the results. In Part 1, we take a look at biopharma therapeutics, now and in the future…

The current state of play

When survey respondents were asked to select the most commercially important biopharma therapeutics available right now, the top answer was monoclonal antibodies (73 percent) – see Figure 1.

“The results align with my own thoughts, as both mAbs and vaccines are growing in significance – especially as the greatest contributors to human longevity continue to be access to clean water, antibiotics, and vaccinations,” says Steve Arlington, President of The Pistoia Alliance. “In the future, their importance to biopharma will depend on the discovery of therapies to treat unmet medical needs, and, in particular, dementias, such as Alzheimer’s, which are becoming more prevalent as our life expectancy increases. We are seeing mAbs, both when used as single therapies or in combination therapies, revolutionize survival rates in many areas of oncology. People also need to realize that mAbs must be used in conjunction with other procedures, such as diagnostics and scanning. The use of mAbs alone will not be enough.”

John Bournas, President and CEO of The International Society for Pharmaceutical Engineering (ISPE), also agreed that mAbs would be important as potential treatments for Alzheimer’s. “mAbs formed the foundation of the industry and will continue to be financially important, even while cost pressures drive firms to seek manufacturing efficiencies,” he says. “Many potential Alzheimer’s treatments are mAbs, and one or more successes in this space would make mAbs production technology and capacity critical for years to come.”

Vaccines were ranked by survey respondents as the second most commercially important biopharma therapeutics. “Vaccines have always been one of the most important class of products for battling infectious diseases – and we should continue to put effort into these to improve quality of life in developing countries. However, their promise for preventing more complicated diseases, such as cancer, is in its infancy, and may not be as broadly applicable as we would hope,” says Marc Bisschops, Director Continuous Bioprocessing at Pall Biotech. “For the immediate future, I definitely agree that mAbs (and mAb derived therapies) will remain the most important class of biopharmaceuticals.”

Therapies of the future

When asking survey respondents what the most commercially important biopharma therapeutics in the next 5–10 years were likely to be, mAbs remained the top answer (56 percent) – as predicted by our experts above – but cell and gene therapies also ranked very high (Figure 2). Bournas says, “Which therapies are most ‘commercially important’ depends on the definition of importance – for the commercial market, mAbs will be important; however, cell and gene therapies will play an important role in the development of new products.”

It’s clear that these cell and gene therapies offer much hype – and so far clinical results are justifying the excitement. However, the Power List members we spoke with, while acknowledging the great potential of these therapies, believe there is still work to be done. In particular, they say it may very well take longer than 10 years for real transformation to be seen.

“The development of cell therapies and gene therapies will move very fast, but personally I think it is unlikely that they will be as important as mAbs in the next 5 to 10 years. It may take a bit longer than that because of the more complicated method of action, as well as manufacturing and administration challenges,” explains Bisschops.

Hal Baseman, Chief Operating Officer of Valsource, also agrees that the cell and gene therapy field may come with teething issues. “In my opinion, advanced therapy medicinal products, such as cell and gene therapies, definitely come with processing challenges. They represent a significant shift from large-scale to small-scale manufacturing methods, and changes in validation, testing, and regulation. Despite this, the field provides opportunities for new companies, facilities, and manufacturing approaches. To what extent this results in a significant increase in product doses remains to be seen.”

Another challenge is commercialization. Arlington says, “At the moment, regardless of whether a breakthrough is on the horizon, pharmaceutical companies can’t work out how to make money from the treatment. Many challenges exist in the process of developing cell and gene therapy treatments, with the additional concern over how a company would deliver and successfully commercialize such a product. The current structures within healthcare providers make it difficult to see attractive delivery models to make these therapies cost effective and commercially viable. We believe this can be overcome, but probably not within the next decade.”

All of this said, such therapies should have a significant impact on human health, in the long term. Bisschops adds, “These therapies could easily become as important as mAbs in the future. Contrary to mAbs, these therapies should – in principle – allow a more sustainable cure for very complicated diseases, such as cancer and auto-immune diseases.”

Ideas and innovations

Cell and gene therapies also stole the spotlight in another part of the survey, when respondents were asked what they considered to be the most exciting therapeutic innovation in recent times (Figure 3). Cell and gene therapy made the top spot by a large margin (57 percent). For the most part, experts from our Power List agree. Bournas says, “Cell and gene therapies are very exciting – the approval of the first product brought us closer to advancing personalized medicine. RNA therapies are another exciting and innovative area of advancement. These therapies have attacked brutal diseases with great success, and that is what makes them so cutting edge.”

“From a therapeutic perspective, personalized medicine and advanced therapy medicinal products are exciting,” says Baseman, “but they and other therapies will also provide the opportunity to  develop and advance innovative sterile product manufacturing and process control approaches. From a manufacturing perspective, I’m very interested in continuous process manufacturing and the use of manufacturing intelligence, such as big data, virtual reality, artificial intelligence, robotics and full automation.”

Other new drugs are also emerging too, and Bisschops says we should not overlook other science. “The first approvals of cell therapy have definitely been exciting,” he agrees. “But I’d also like to add that all of the work on existing biological therapies has resulted in a great accumulation of knowledge and fantastic science that helps us understand complicated diseases and the biology of the human body much better. This should enhance our ability to cure these diseases.”

Arlington, however, adds that true innovation takes time. “Though there is a lot of great science occurring, I would say there haven’t been any innovative breakthroughs related to specific therapies that have excited me recently,” he says. “The innovations that we’re seeing today have been in the works for many years. This is not unusual, and it takes considerable time to reach the proof of concept stage. There are promising leads yet to be confirmed in the oncology field and in non-alcoholic steatohepatitis. Right now, there are certain areas that are gathering speed, such as companion diagnostics, which show great promise and will help to make precision medicine a reality. But despite their potential, the likes of FDA and EMA still need to work out how best to regulate the area before companion diagnostics can be speedily adopted.”

The challenges of scientific progress were also acknowledged by survey respondents. Respondents were asked for their thoughts on the most challenging issues that arise when bringing new biopharma therapies to the market (Figure 4). The issues that respondents felt would be most challenging were the scientific complexities in discovering effective therapies for unmet medical needs and the duration and cost of the drug discovery process. A number of respondents also pointed to the challenges of manufacturing, which Baseman is also concerned about.

“Trying to fit existing manufacturing approaches, regulatory expectations and guidance to the manufacturing methods needed for new therapies is a challenge,” he says. “Traditional approaches to manufacturing, testing and process control may not necessarily align with new therapy manufacturing methods. Trying to force fit these methods may not be the best way to proceed.”

Meanwhile, Bisschops is particularly concerned about the manufacturing hurdles of cell and gene therapies. “For recombinant proteins, vaccines and mAbs, processes are well understood by regulators and biopharma companies, but it is different for newer therapies. Recent successes have demonstrated that there are approaches that work for cell and gene therapies, but it is yet unclear how this will eventually work out. To make it an affordable and scalable process, adequate strategies for manufacturing need to be developed. For instance for cell therapy, the current strategy seems to be to harvest cells from the patient and have them sent to a specialized facility for applying the cell therapy. Once the cells are treated (tested and released), they are sent back to the patient for administration. There may be room for improving the logistics of this treatment, reducing patient risks, inconvenience and costs.”

Come together to succeed

Finally, we asked our Power Listers for their advice on what biopharma needs to focus on to rise to the challenges that lay ahead for the field. The key theme is collaboration; the industry must work together to overcome the issues facing the industry.

Arlington: “It is becoming more difficult for individual biopharma companies to come up with answers to industry challenges by themselves. More collaboration is needed at all stages of the R&D process – and regulators and HTAs need to be involved much earlier. Coming together and releasing pre-competitive information will allow the industry to share best practice, enjoy increased efficiency, and reduce costs across the board. As one example, The Pistoia Alliance is involved in a project to increase knowledge of antibody structures – which determine their specific interactions with antigens – in the public domain.”

Baseman: “Scientific and risk-based critical thinking is needed to challenge existing methods and develop innovative and more effective manufacture and process control approaches. A partnership of manufacturers, technology suppliers and regulatory health authorities is the key. Sharing of information between these groups, and across these groups, would reduce the uncertainty and risk of new technologies and approaches. Modernization of manufacturing facilities and processes, and easing of restrictive and burdensome global post-approval change requirements are also important to reduce barriers to innovation.”

Bisschops: “I agree; the biopharma community must work together. We all need to realize that we are serving the health of our society – a truly noble goal. A collaborative approach between sponsors, patient organizations, regulatory agencies and suppliers will result in strategies and solutions that eventually provide the most added value to society as a whole – and therefore benefit all partners in the biopharmaceutical community.”

Bournas: “The collaboration of industry and regulatory bodies will pave the way to mastering the new manufacturing paradigm. This is the core of my work at ISPE – the society aims to bring industry and regulators together to work through industry challenges with an open mind to new approaches. Preparing the workforce of the future is also an important initiative for the industry. Workforce availability is a challenge right now – does the industry have the workforce with the right skills to handle the new technologies being developed and the new ways of manufacturing? The Global Pharmaceutical Manufacturing Leadership Forum (GPMLF), in collaboration with ISPE, is taking a close look at industry workforce challenges, and working with industry and academia to identify the skills and training needed by students and young professionals coming into the workforce. They are the future of our industry.”

Indeed, skillsets and training are imperative for the future of the industry – and we’ll be tackling this topic in the second article of this series, which will be published in the August issue of The Medicine Maker.

Meet the Experts

Steve Arlington

President, The Pistoia Alliance 

Steve is a Champion of Change on our 2018 Power List because of his work with the Pistoia Alliance. He is passionate about greater collaboration within and between industry, the regulator, the payer, and the provider. Previously, he was Global Lead Partner, Pharmaceuticals and Life Sciences consulting, at PricewaterhouseCoopers.

John Bournas

President and Chief Executive Officer, ISPE

John has been a member of the Power List since 2017. He is responsible for developing ISPE’s global initiatives and business operations, and also leads the organizational efforts in solidifying working relationships with international regulators. Like Steve, he is passionate about collaboration, as well as training the workforce of the future.

Marc Bisschops

Director Continuous Bioprocessing, Pall Biotech

Marc’s work with continuous chromatography and continuous downstream processing earned him a place on the 2018 Power List. He is listed as an inventor on various patents related to continuous process technologies. He hopes to help the biopharma industry become more efficient and agile.

Harold (Hal) Baseman

Chief Operating Officer, ValSource

Hal has over 39 years of experience in the pharma industry and has also been very active in the Parenteral Drug Association, including a stint as Chair. He has been a leader, author, editor and contributor to numerous technical reports, articles, books, and presentations. He is an Industry Influencer on our 2018 Power List.