October 15, 2018 (Vol. 38, No. 18)
Eric S. S. Langer President and Managing Partner BioPlan Associates
Critical Focus on Biomanufacturing Efficiency and Productivity
The biopharmaceutical industry is dynamic and complex, and BioPlan’s 2018 15th Annual Report and Survey of Biopharmaceutical Manufacturing indicates the industry continues to expand. As part of our annual analysis, we surveyed 222 biopharmaceutical decision-makers at developer and contract manufacturing organizations (CMOs) across 22 countries.
In this year’s study, we found that the biopharmaceutical industry is evolving and demanding new and improved technologies to reduce costs, increase efficiencies, and improve weak development pipelines, especially in developing economies. Facilitating this trend of growth are the incremental innovations in improved manufacturing productivity. We project an optimistic future vision that includes the likelihood of more:
- Biopharma facilities worldwide (especially in major markets as well as in Asia)
- Biological products (but often each with smaller markets)
- Follow-on products and manufacturers (including biosimilars and biogenerics)
- Flexible manufacturing facilities (including those used for the manufacture of multiple products)
- Modular facilities
- Cloned facilities in developing countries
- Regional cellular/gene therapies manufacturing
- Adoption of single-use systems at clinical- and ultimately commercial-scale production
- Efficiency in bioprocessing as titers and yields continue to increase
- Use of continuous processing (including for downstream processing)
- Diverse products in development and marketed (e.g., cellular and gene therapies)
- Automation, monitoring, and process control
- Use of bioprocess modeling, data mining, PAT, and QbD
- Use of high-tech expression systems and other genetic engineering advances
- Complex regulations which drive many other specific needs and advances
Bioprocessing innovations are being driven by a number of major industry trends. Below we note a few trends that were cited in this year’s study.
1. Manufacturing productivity/efficiency remains top concern. When asked to cite “the single most important trend or operational area,” 16.0% of the respondents said “manufacturing productivity/efficiency.” With this largely unchanged from last year, productivity associated with cost-savings continues to be a major concern. See Figure 1.
2. Bioprocessing productivity continues to increase. Bioprocessing productivity is consistent with survey data having shown steady increases in bioprocessing efficiency, particularly upstream bioprocessing. For example, in the study, we found that the average titer for mAb manufacturing at both clinical and commercial scales is 3.20 g/L. This has risen very significantly through the past decade.
3. Biosimilars/biogenerics bring more products and players. The Biosimilars/Biobetters Pipeline Database now reports 1000 biosimilars/biogenerics in development or being marketed worldwide, including 165 in trials and 380 being marketed. There are also 560 biobetters in development or being marketed, with 217 in clinical trials. Over 750 companies are involved in follow-on products. Within five years, biosimilars and other new follow-on biopharmaceuticals may outnumber reference biopharmaceutical products, even in the U.S. market.
4. Facility constraints create bottlenecks, prompting calls for continuous downstream processing. This year, the most cited factor reported as likely to cause capacity constraints at respondent facilities in five years was “facility constraints,” with this remaining the number-one-cited factor since we started to ask this question in 2008.
5. Industry seeks lower manufacturing costs. A majority of respondents (64.0%) reported their facility has “implemented programs to reduce bioprocessing costs.” The second-most-commonly cited cost-reduction activity was “negotiated harder with vendors to reduce costs,” at 41.3%. This is the first year we surveyed regarding average cost/gram for recombinant protein manufacture, which is now $306.8/gram.
6. Biopharma industry and supplier growth is healthy. The industry and its supply sectors, both equipment and services, have grown consistently at ~12–14%/year in terms of revenue over the past 20+ years, and this trend continues. This year, suppliers reported an average of 13.7% revenue growth, with “equipment and instrumentation” having the highest growth at 16.8%. See Figure 2.
7. Bioprocessing budgets continue to increase. Respondents reported an average 8.2% increase in their 2018 facility bioprocessing budgets. This year, no budget decreases were reported in any of the areas surveyed.
8. Use of single-use systems is still growing. Adoption of single-use systems continues. BioPlan estimates that ≥85% of precommercial (clinical and development scales) product manufacturing now involves primarily single-use systems. This adoption will increase as more new products being developed are using single-use systems to advance to commercial manufacturing.
9. Continuous bioprocessing innovation is in demand. Continuous bioprocessing is an area in which respondents saw the need for improvements. When asked to identify the areas where suppliers should focus their development efforts, the second-most cited area by over one-third of the respondents (37.8%) was “continuous bioprocessing, downstream, [and] chromatography.”
10. Bioprocessing capacity growing, particularly in Asia; cell/gene therapy capacity shortages exist. BioPlan’s database (www.Top1000Bio.com) ranks the top 1000+ bioprocessing facilities worldwide based primarily on bioreactor capacity. Leading capacity holders are: 6 million L (37%) in the U.S./Canada; 5.5 million L in Western Europe (33%). Asia retains around 25% of global capacity. T
here is no ongoing bioprocessing “capacity crunch,” with only 10.5% of respondents reporting “severe constraints” at commercial scales at their facility. However, there is a “capacity crunch” affecting cellular and gene therapies.
11. Hiring in bioprocessing a continuing problem. Hiring of bioprocessing professionals is a problem area. “Process development staff, upstream” was reported as the most difficult area to fill, cited by 40.8%, followed by “process development staff, downstream” at 40.0%. See Figure 3.
12. China on track to become an industry leader. Significant growth in the biopharmaceutical industry is occurring in China, as it has moved recently ahead of India in terms of bioprocessing capacity. This year, China is the most cited destination for likely outsourcing in five years, cited by 25.4% of respondents.
These factors are driving many of the ongoing biopharmaceutical advances. The current situation in biopharma is exciting, with new technologies and markets, such as biosimilars, cellular and gene therapies, and many new opportunities in emerging markets.
1. 15th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, BioPlan Associates, April 2018.