It’s probably fair to say that innovation in the biopharmaceutical manufacturing industry is a slow cycle. But that would ignore the many changes in biomanufacturing over the past 5 to 10 years: Better expression systems, widespread adoption of novel single-use applications, re-emergence of perfusion technologies, new modular and flexible facilities, better sensors, control systems and downstream technologies.
The industry now finds itself very aware of the promise new technologies carry in terms of optimizing, and in some cases revolutionizing existing processes. Results from our “10th Annual Report and Survey of Biopharmaceutical Manufacturers”1, in which we surveyed 238 biomanufacturers, indicate that end-users are still actively looking for a range of new technologies to solve persistent problems.
MORE FOR LESS
The driving factors today in bioprocessing innovation, according to our study, involve improving efficiency and productivity. This equates to getting more out of existing processes for less money. For example, roughly two-thirds of the industry attributes improvements in manufacturing performance to single-use systems and applications. But most of the recognized benefits involve improved efficiency, especially in clinical-scale processes. Single-use devices shorten the time getting facilities up and running and reduce capital investments necessary for new plants. New facilities offer more flexibility, and “modular” approaches along with faster campaign turnaround times and lower annual maintenance costs.
Similarly, the industry is demanding better downstream processes — demands that are generally focused on cheaper, equally effective chromatography, protein-A and purification steps. Again, innovations need to be about cost effectiveness. So as innovators and suppliers develop new products, they’ll need to demonstrate their technologies are actually better than current approaches.
PRODUCTIVITY INNOVATION 2013
In a separate survey Bioplan Associate’s ran late last year, among the more than 450 global subject matter experts and senior participants who make up our Biotechnology Industry Council,2 the study found consistent expectations regarding improvements in productivity. Again, improvements in downstream processing and single-use technologies ranked as the top 3 trends for 2013, these were followed by demands for better analytical methods. New analytical methods are required for better process monitoring and process improvements. In addition, to develop biosimilars, the industry needs better characterization techniques, and better processes. Otherwise, even if “similarity” with a reference biologics could be shown, the cost of producing a new biosimilar might not be much lower than the original; this could dramatically reduce the attractiveness of any such high-cost generic version.
Returning to the attractiveness of single-use technologies, we found in our annual survey that respondents today estimate 35% of their upstream clinical production operations to be single-use. This compares with 25% of respondents that said more than 80% of their downstream clinical production steps are now single-use. The number is 16% of downstream commercial-scale production. This wasn’t surprising to see that the lowest use was for downstream commercial production, which remains mostly fixed stainless-steel equipment. It was also fairly consistent to see the highest adoption rate be for downstream clinical production, likely due to broader use of disposable tubing and filters, buffer containers, etc.
FOCUS SUPPLIERS, FOCUS
Researchers asked respondents to consider new product and services developed by suppliers and to identify the top areas they want suppliers to focus their development efforts on. This year, of the 21 areas the study listed, the areas highlighted in prior years, and other studies continue to occupy the top position. Specifically:
- Disposable products, including bags, connectors and other devices
- Better probes and sensors
- Process development services (up- and down-stream)
- Chromatography products
Some of the specific new product development areas being demanded by biopharma’s operational managers are included in Figure 1. Identification of these areas by end-users is not a reflection of their need for technical advances to produce drugs that otherwise wouldn’t be possible. Rather it mirrors their requirements to produce more efficiently and less expensively. This shift in focus on manufacturing is a maturation process that has been growing over the past 10 years.
TRENDS OVER TIME
Looking at responses from the past four years, the study shows that interest in more innovative approaches to bioprocessing, again, centers on process improvements. For example, demand for better upstream process development services has increased five percentage points over the past four years, while interest in downstream PD has decreased from a high of 35% in 2008, down to 26% this year. Similar declines in interest in new chromatography products are evident. This suggests the acute bottlenecks created around downstream operations have been abating, while the chronic need for improved productivity has not.
Better disposable devices, including bags and connectors, has increased by about five percentage points from 2008. Demand for disposable probes and sensors is up by roughly 10 percentage points, while interest in new bioreactors and purification products has remained steady during the period.