Viewpoint: 2018 a Critical Year for Maturation of European Bio Supply Chain

Rutger Oudejans, brand director of bioLIVE-a new biopharma event taking place in Madrid from 9-11 October 2018-explains how Europe's growing biomanufacturing and bioprocessing industries will develop during the next year and why it is such a crucial time for the small-molecule and biopharma industries to integrate in order to facilitate growth.

Over the past couple of years, Asia has come to the forefront of investment in biopharma companies and supporting biotech-based equipment, materials, and system, with Singapore, Korea, and China all growing in prominence. China is now ahead of regions in Europe, only trailing behind the US biotech hubs of Boston, San Diego, and San Francisco. With excess capital to deploy, China has focused much of its investments in the United States, and, to a lesser extent, European Union (EU)-based biotech companies due to cheaper biotech stocks-compared with highly priced Chinese biotech stocks-and to internationalise and cover more markets (1,2). Companies in China in particular have a shortage of experienced personnel, so it is likely that they will continue to seek Western partners to gather their expertise across a wide range of bio-disciplines.

As the industry shifts towards a data-driven model for new drugs, tools such as artificial intelligence (AI) are set to enhance R&D productivity and lower overall costs. Because innovators will be looking for companies that can potentially add value in R&D, we predict this new supply of capital from China will offer smaller biotechs in the US and Europe an opening to tap into AI capabilities, genomics, and precision medicine (2).

To access manufacturing facilities, the most common route for small biopharma is to form relationships with contract development and manufacturing organizations (CDMOs). There is good value in biopharma companies diversifying their approach to fulfilling the supply chain by both manufacturing in-house and outsourcing, as it minimizes risk of shortages and enables them to be flexible in meeting demand. Granted, this brings about other complexities like ensuring a standardized quality between different facilities.

Additionally, AI and automation in Europe are on the rise both in the manufacturing of equipment; GE Healthcare’s use of cobots (collaborative robots) in Sweden is one example, and in the production of biologics (3). But in terms of overall capacity, Asia is now rapidly expanding and will approximately double its manufacturing capacity from 2016 to 2021, while Europe will increase by more than 50%. The North American market will also increase, however much less significantly, at around 25% (4). The resultant landscape for overall capacity will be much more evenly split between the three regions by 2021, with the North American market shrinking from an approximately 50% capacity share down to about 34%. In addition, it is thought that China and India now represent the largest growth markets for biomanufacturing, further emphasising the rapidly changing dynamics and increased internationalization (5).

Expansion in emerging therapies

Another growth area particularly within the outsourced supply chain is antibody-drug conjugates (ADCs), perhaps the most natural crossover between the worlds of small and large molecules. There are currently four products on the market, counting the launch of Pfizer’s Besponsa and Mylotarg in 2017; European companies such as ADC Therapeutics are advancing targets into clinical trials (6).

It is common for big pharma to source secondary supply chains for the development of newly patented projects, and most often it is to biomanufacturers either in the US or Europe. What is interesting is that we are also seeing US biotechs bringing development projects to Europe, as well as a rising biotech industry here. This is in part due to recent EU expansions by a number of companies including but not limited to Lonza, Piramal, Novasep, Abzena, Carbogen Amcis, and ADC Bio. But it also marks a maturing of the ADC pipeline and is reflective of the increased targets coming to market.

Even in the cell- and gene-therapy sector, often viewed as a US-centric industry, we are seeing increased collaborations across Europe thanks in part to initiatives like the United Kingdom’s Cell and Gene Therapy Catapult. Newer public-private collaborations and initiatives will be especially important as there is forecast to be a rapidly increasing capacity shortage, with more development programmes and limited new capacity available. But with the US FDA’s recent approval of Kymriah, the industry may now be at the tipping point where more widespread approvals will begin to appear; the question is, how will the supply chain adapt to smaller niche volumes?

In fact, of the forecasted demand, approximately 70% of new bio products coming to market between 2016 and 2020 are expected to be in the 100 kg per year per product category or less, with the exception of treatments for Alzheimer’s, asthma, cholesterol, and other applications (4). This means that much of the newer capacity can and will be met by single-use bioreactors, but the majority of the large-scale growth will be from generic monoclonal antibody drugs coming off-patent by 2020 (7).

The Biosimilars/Biobetters Pipeline Database reports that nearly 850 biosimilars (including biogenerics) and more than 515 biobetters are in development or being marketed worldwide, with 125 and 200 in clinical trials development, respectively (8).

Emerging bioprocessing technologies

CDMOs are most likely to pioneer the use of new technologies that offer greater manufacturing flexibility and efficiency, given they must develop standardised manufacturing platforms across a variety of processes and products for their customers, each with their own bottleneck hurdles to overcome. For example, in response to the threat of capacity constraints during production, we will see a surge in the development and application of continuous bioprocessing technologies and disposable, single-use products by CDMOs, especially for patient-cohort drugs where volume is less important (9).

What may ease the pressures on biomanufacturers is the Technology Roadmap for the Biopharmaceutical Manufacturing Industry, the first edition of which was published in July 2017 by the BioPhorum Operations Group (10). It is clear that it is significantly more cost-effective to develop technologies and industry standards in collaboration compared to individually. This map, the result of a global industry collaboration between 33 companies, defines the needs and challenges of biomanufacturers based on the current industry trends and openly confers them to their key stakeholders, including academic institutes, supply partners, regulators, and government agencies, so that they can all align their distinct visions and strategies toward the common goal of high quality and affordable medicines.

The Roadmap is designed to use metrics to highlight deficiencies in the four drivers in the biopharma industry-speed, flexibility, cost, and quality-to find a solution in the pre-competitive space. As the industry evolves and new challenges and technologies arise, the map will be updated accordingly. We expect this will advantageously impact project success across the industry in the long-term and accelerate innovation worldwide.

Regulatory and political issues

The industry must also consider the implications of the success of the Marketing Authorization Holder (MAH) pilot plan in China, which allows the outsourcing of manufacturing to CDMOs for the first time. Before this, Chinese companies had to manufacture all products in-house and therefore invest in facilities to get China Food and Drug Administration approval, which often made producing a new drug unviable; foreign companies would have to use the expensive imported drugs pathway. If the MAH system, which runs until November 2018, is continued throughout the whole country, it will transform the face of biopharmaceutical innovation in China. Not only that, it will open up the market for manufacturing in China by European biotech companies now that they have the option to get a license and manufacture there (11). So, during the next year, we should see more Western products entering China-even those from European partners.

With Brexit looming, the future of the supply chain in Europe is oblique, because a large portion of biomanufacturing is performed in the UK. Most likely, there will be fundamental changes for the industry in the long-term (e.g., how biopharmaceutical ingredients are sourced). In the meantime, biopharma may be more reluctant to invest further in the UK due to the uncertainty. The relocation of the European Medicines Agency (EMA) from London to Amsterdam is just another one of the many consequences of the UK leaving the EU. It is a move that may inadvertently assist in growing the biopharma market in the Netherlands and nearby regions (e.g., Paris, Belgium, Western Germany) by attracting companies that wish to have sites close to the regulator, as well as the host of regulatory consultancy firms and experts (approximately 36,000 annual visits) that go along with it, providing services to manufacturers (12).

The most important biotech markets will remain as North America and Europe-the former being considerably more mature. With the capacity limitations currently facing European biotechs, there is an opening for the market to grow or internationalize. New technologies to tackle these issues will emerge; continuous manufacturing and in particular single-use technology are already quite well established. At the moment, European biotechs are still looking to partner with European firms; however, during the coming years, there will be more outsourcing to China and India especially if their industries continue to be the fastest growth markets. Only recently, WuXi Biologics opened the world’s largest single-use facility (13) and the massive overall capacity increases at Samsung Biologics are also well documented (14).

Our research has shown that we are at a critical time for the industry’s development, particularly in Europe. During the next year, we hope to help accelerate this growth and potential by bringing the biotech, bioprocessing, and manufacturing supply chains together. But what we feel is really going to make a contribution, larger than the sum of its parts, is providing the lessons learned from across the small-molecule space and applying these to the developing biopharma sector. There is a natural maturation of the bioprocessing and manufacturing markets currently underway, but overall there is still a shortage of biomanufacturing capacity and an increasing reliance on third-party supplies. That is why bioLIVE will be so crucial in helping to create those supply networks and introduce many of the needed contacts, not to mention that more than half of the industry is also looking to make capital investments over the next year.

For Europe to accelerate growth, we need the industry to diversify and deepen its networks, and that is without even considering the competitive effect of biosimilar development in India and China’s massive bio investment prospects. The next year will be a key time for industry across to the globe to set up the right partners and infrastructure to ensure they are able to capitalise on the industry’s growth potential, which for the supply chain will run in excess of double digit rates.

References

1. C. Chen, “Chinese Investors Have Money, Want Biotech and Don’t Fear Trump,” Bloomberg Markets, Jan. 10, 2017.
2. EY, Biotechnology Report 2017: Beyond Borders – Staying the Course, 2017.
3. GE, “GE Healthcare Opens Its First European 3D Printing and Design Center,” Press Release, Oct. 3, 2017.
4. P. Seymour and D. M. Ecker, “Global Biomanufacturing Trends, Capacity, and Technology Drivers: Industry Biomanufacturing Capacity Overview,” American Pharmaceutical Outsourcing, Jun. 30, 2017.
5. Survey Report: State of the Global Biomanufacturing and Bioprocessing Industry 2017, Biopharma Reporter, Oct. 19, 2017.
6. ADC Therapeutics, “ADC Therapeutics Announces Closing of $200 Million Private Financing to Fund Two Lead Programs Through Registrational Trials,” Press Release, Oct. 23, 2017.
7. “Biopharmaceuticals/ Biosimilars Roundtable,”American Pharmaceutical Review, Dec. 22, 2017.
8. Biotechnology Information Institute, Biosimilars/Biobetters Pipeline Directory.
9. J. Miller, “CMOs Must Embrace Flexible Manufacturing,”Pharmaceutical Technology, Outsourcing Resources Supplement 2017, Aug. 1 2017.
10. BPOG, “BioPhorum Operations Group Launches its Technology Roadmap for the Biopharmaceutical Manufacturing Industry,” Press Release, Jul. 20, 2017.
11. E.J. Lane, “China Pilot Eyes Easier Marketing Authorization,” FiercePharma, Jun. 19, 2016.
12. “Moving Times,” PM Live, Oct. 16, 2017.
13. WuXi Biologics, “WuXi Biologics Initiated cGMP Manufacturing in the World’s Largest Biologics Manufacturing Facility Using Only Single-Use Bioreactors,” Press Release, Dec. 6, 2017.
14. “Samsung BioLogics Says 180,000L Plant is Completed but Not Validated,”BioPharma-Reporter, Dec. 1, 2017.