- Language: English
- 1027 Pages
- Published: October 2011
- Region: Global
The State of Mammalian Cell Culture Biomanufacturing
- Published: January 2011
- Region: Global
- 150 Pages
- BioProcess Consultants
BioProcess Technology Consultants offers unique, actionable information resources for the biopharmaceutical industry. The insightful analysis in our reports is designed to help decision makers build and put to work comprehensive business and technical strategies for the complicated topics covered.
This report offers an in-depth review of the growth in sales and production demand for biopharmaceutical products currently on the market and in development. The report provides a comprehensive analysis of the current and future supply and demand for mammalian cell culture capacity, including the geographic distribution of manufacturing capacity, the impact of facility utilization rates on overall capacity requirements, and the influence of emerging technologies on manufacturing facility design and utilization.
Drawing from BPTC®'s proprietary Biopharmaceutical Product database, this report highlights the continued growth of total biopharmaceutical sales in 2010 to $107 billion, or approximately 12% of the total pharmaceutical market. We review the production methods used for the top biopharmaceutical “blockbuster” products and analyze the impact of those produced in mammalian cell culture on global manufacturing capacity showing that despite the continued growth in sales of these products and the associated requirement for increasing mammalian cell culture capacity to meet this market demand, overall capacity utilization rates have remained low due to technological advances. Our analysis shows that industry-wide capacity utilization will increase approximately 50% from 2011 to 2016 as construction of new capacity slows and more products reach the market.
The impact of this increasing utilization rate on biomanufacturing capacity and the current concentration of this capacity in a small number of companies may limit some company's ability to access capacity in a timely manner. While the five product companies controlling the majority of cell culture manufacturing capacity have more than enough capacity to accommodate their anticipated future needs and keep their own utilization rates low, many of the remaining companies, which either have smaller-scale manufacturing capacity or are relying on CMOs, may find a need for additional capacity by 2016 suggesting that CMOs and smaller biopharmaceutical companies may announce the installation of new capacity in the coming years.
This 150-page report provides an unrivaled analysis of the drivers of biomanufacturing supply and demand. With 38 figures and graphs and 27 tables, including a comprehensive list of sales data and bulk product requirements for all biopharmaceutical products produced in mammalian cell culture currently on the market, The State of Mammalian Cell Culture Biomanufacturing provides detailed, data-driven insight into the biomanufacturing market to inform senior executives and program managers with the essential and timely information needed to fully understand the mammalian cell culture biomanufacturing landscape and to stay competitive.
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Table of Contents
1. Executive Summary
Growth of Biopharmaceutical Sales
Sales of Biopharmaceuticals Produced in Mammalian Cell Culture
Production Technology Used for Biopharmaceutical Product Manufacturing
The Contract Manufacturing Market for Biopharmaceutical Production
Currently Approved Biopharmaceutical Products
3. Methods and Assumptions for Forecasting Supply and Demand
Estimating the Demand for Mammalian Cell Culture Capacity
Estimating the Current Biomanufacturing Demand for Commercial Products
Estimating the Future Biomanufacturing Demand for Commercial Products
Estimating Future Commercial Biomanufacturing Demand for Pipeline Products
Expression Levels and Overall Yields
Probability of Success and Time for Advancement of Clinical Products
Comparison of Methods Used for Commercial versus Pipeline Products
Estimating the Supply of Mammalian Cell Culture Capacity
4. Bulk Product Requirements for Biopharmaceutical Products
Bulk Requirements for Currently Approved Products
Forecast Bulk Product Requirements
5. Volumetric Demand for Mammalian Cell Culture Capacity
Forecast Manufacturing Volume Requirements
Products in Development with Potential Large Volume Demand
6. Capacity Projections Through 2
Segmentation of Mammalian Cell Culture Manufacturing Capacity
Contract Manufacturing Organizations
Excess Capacity Companies
Current Supply of Mammalian Cell Culture Capacity
Growth in Mammalian Cell Culture Capacity
Who Controls Capacity?
Geographic Distribution of Mammalian Cell Culture Capacity
Clinical versus Commercial Manufacturing Capacity
Projected Manufacturing Capacity by Scale
7. Single-Use Technologies in Biopharmaceutical Manufacturing
Single-Use Bioreactors in Biopharmaceutical Manufacturing
Single-Use Technologies for Downstream Processing
The Impact of Single-Use Technologies on Manufacturing Capacity Utilization
Supply Chain Challenges and Opportunities for Single-Use Technologies
8. Overall Balance of Mammalian Cell Culture Supply and Demand
9. Capacity Utilization
Capacity Utilization at the Top Five Top Companies with Cell Culture Capacity
10. Additional Sensitivity Analyses
Success of Product Candidates Currently in Clinical Development
Increases in Product Titer
11. Impact of Biosimilars on the Demand for Mammalian Cell Culture
The Current Market in Biosimilars
The Driving Force for Interest in Biosimilar Development
Biosimilar Products in Development for the US and Europe
Biosimilars in Development Outside the US and Europe
Will Biosimilars Affect Capacity Demand?
This report provides an in-depth analysis of factors influencing the global utilization of mammalian cell culture manufacturing capacity for biopharmaceutical production. In addition to providing an overview of current capacity utilization in the biopharmaceutical industry and forecasting the supply of and demand for mammalian cell culture capacity through 2016, the also report includes detailed information regarding many important aspects of the biomanufacturing market. Since the 2008 publication of our original report analyzing the supply and demand for mammalian cell culture capacity, a number of the trends highlighted in the original report have continued to develop and increase in importance. These include technological advances in manufacturing processes, particularly related to the increased acceptance of single-use or “disposable” bioreactors and technologies, improvements in expression levels, continued development of biosimilar and biobetter products, and continued consolidation in the pharmaceutical and biopharmaceutical industries. The growing adoption of single-use technologies for the manufacture of biopharmaceutical products and the emergence of biosimilar products worldwide are of such importance to the supply and demand of mammalian cell culture capacity and to the design of manufacturing facilities of the future that we have devoted separate chapters to a review and analysis of each.
Demand for biopharmaceutical products, especially monoclonal antibody-related products, continued to grow at a very healthy pace in 2010 with total biopharmaceutical sales reaching $107 billion, or approximately 12% of the total pharmaceutical market. In 2010, there were 29 biopharmaceutical “blockbuster” products with annual sales over $1 billion, of which over 60% were produced in mammalian cell culture. Five of the top ten selling pharmaceutical products are now biopharmaceuticals. These products, Remicade, Enbrel, Humira, Avastin, and Rituxan, combined with the long list of monoclonal antibody products in development make monoclonal antibodies the fastest growing class of biopharmaceutical products.
Despite the continuing growth in demand for these products and the associated requirement for increasing amounts of mammalian cell culture capacity, ongoing advances in cell culture process yields coupled with the significant capacity expansion of the last decade, continue to keep industry-wide utilization rates low.
The industry-wide utilization of mammalian cell culture capacity for 2011 is expected to be 44%, increasing to approximately 65% in the coming five years. Estimates of the industry-wide utilization of mammalian cell culture capacity have dropped in recent years due to a number of factors, including:
- The addition of significant new manufacturing capacity during the past five years as a result of plant construction decisions that were made early in the decade
- The dramatic improvements in expression levels and overall process yields that are now achievable, especially in the production of monoclonal antibodies, resulting in significantly greater productivity per unit of capacity
- The slower rates of approval of new “volume driver” products that would create significant demand for cell culture manufacturing capacity similar to the high capacity needed to meet the market supply of products such as Enbrel, Avastin and Rituxan
Along with the slowdown in construction of new capacity, the mothballing and divestitures of existing manufacturing facilities coupled with the continued growth in sales of existing approved products, approval of new products, and introduction of biosimilars, will drive the gradual increase in industry-wide capacity utilization. As the existing “volume driver” products mature and their growth rates slow, demand for mammalian cell culture capacity will become more predictable compared to a decade ago. Additionally, new products, both innovator products and biosimilars, will likely require less capacity per product due to increases in productivity. As a result, absent any significant unforeseen market disruptions, it is unlikely that there will be significant industry-wide capacity shortages in the coming five year period.
The utilization of mammalian cell culture manufacturing capacity can vary significantly due to a number of factors including whether the capacity is used primarily for commercial or clinical production, the number of products being produced in a facility, the ability of the facility to support concurrent production or multiple batches of the same or different products, and the assumed theoretical maximum number of batches a given production bioreactor can be used to produce in a given year. A number of sensitivity analyses have been performed to assess the impact of these and other factors. Due to the time and regulatory constraints required to transfer manufacturing processes between different manufacturers or different manufacturing sites, it is difficult, if not impossible, for the biopharmaceutical industry to operate efficiently at 100% capacity utilization. We believe that companies will begin to experience difficulties in meeting product demand or efficiently manufacturing all products when industry-wide utilization rates approach 80%. In most of the cases we examined, the industry-wide utilization rates are forecast to remain below 80% during the next five years, although in some scenarios the utilization rate does exceed 70% and in one case exceeds 100%. Nevertheless, while utilization rates will undoubtedly increase in the next five years, industry-wide capacity shortages are unlikely during this period.
We also provide detailed information and analysis of the distribution and control of manufacturing capacity and the trends in this area. While there is a gradual trend towards increasing capacity share for CMOs and “Excess Capacity” companies (companies who develop their own biopharmaceuticals but also offer contract manufacturing services), product companies continue to own more than 70% of the industry-wide mammalian cell culture capacity. Despite the continued growth of the world-wide biopharmaceutical market and the addition or expansion of capacity in Asia and the developing world, the majority of large scale mammalian cell culture capacity will remain in the US and Europe. Companies looking to add or install new manufacturing capacity, especially for the production of biosimilars, will have the option of acquiring existing capacity in the US or Europe rather than building new capacity during the coming five year period.
Despite the growing volume of mammalian cell culture globally, the majority of this capacity is currently held by just ten companies, who collectively own 76% of the total worldwide mammalian cell culture manufacturing capacity. The concentration of capacity in a few companies is even more dramatic in that five companies, Roche (including Genentech), Johnson & Johnson (including Centocor and all other subsidiaries), Boehringer Ingelheim, Amgen, and Lonza, currently control over 50% of the worldwide cell culture manufacturing capacity with Roche alone controlling approximately 20% of the total worldwide capacity.
When comparing capacity utilization rates for the top five capacity holders to the rest of the industry, we see differences in the overall utilization of mammalian cell culture capacity. Not surprisingly, utilization rates for those companies that do not have significant manufacturing capacity of their own is forecast to grow at a much greater pace than for the top five capacity holders. Given that the biopharmaceutical product pipeline is distributed over many companies, whereas cell culture bioreactor capacity is held by only a few, this is not surprising. For those companies holding significant manufacturing capacity, we do not anticipate any capacity shortages or limitations in manufacturing and forecast little to no expansion beyond already announced expansions or renovations with this group of companies.
On the other hand, we anticipate that smaller biopharmaceutical companies that do not currently have their own capacity may find some capacity limitations at CMOs in the next five years. Therefore, we would not be surprised to see smaller companies and CMOs announcing the construction of new or expanded capacity in the coming years. With the emergence of single use technology as a viable option for production of clinical trial material as well as commercial products, we anticipate that many of these companies are evaluating the option of installing capacity to meet future manufacturing requirements. The more flexible and cost-effective facility build-out in shorter time frames than for traditional biopharmaceutical manufacturing facilities, will further more product companies and CMOs to rapidly add additional manufacturing.
The detailed analyses and information provided in this report will be useful to those involved in all aspects of biopharmaceutical manufacturing as well as to investors and executives contemplating investment in mammalian cell culture capacity or any of the underlying technologies and services necessary for the successful manufacture of biopharmaceutical products.
- Acceleron Pharma
- Alexion Pharmaceuticals
- Autek Bio
- Avid BioServices
- BioMarin Pharmaceutical
- BioPharmaceuticals Australia
- BioVitrum AB
- Biogen Idec
- Boehringer Ingelheim
- Bristol-Myers Squibb
- CMC Biologics
- Celonic GmbH
- Cobra Biologics
- Cook Pharmica
- Cytovance Biologics
- DSM Biologics
- EMS/Shanghai Biomabs
- Fujifilm Diosynth Biotechnologies
- Gallus BioPharmaceuticals
- Gedeon Richter
- Human Genome Sciences
- Intas Biopharmaceuticals
- KBI BioPharma
- Kyowa Hakko Kirin
- LG Life Sciencesl
- Laureate Pharma
- Lonza Biologics
- Merck KGaA
- QSV Biologics
- Rentschler Biotechnologie
- STC Biologics
- Samsung Biologics
- Shanghai CP Guojian
- Spectrum Pharmaceuticals
- Toyobo Biologics
- Watson Pharmaceuticals
- WuXi Apptec