CMOs Ratchet up use of Single-Use Devices to Improve Performance

CMOs are on the leading edge of the growth of single-use devices. This growth is partly driven by their highly competitive business model that requires that they continually drive for efficiency and productivity. As an example, today more than 86% of CMOs are using disposables/single-use devices to create improvements in bioprocessing performance, according BioPlan Associates' 20th annual report (1). The survey asked 352 global biomanufacturers and CMOs which aspects of manufacturing technology have improved performance at biologics facilities over the last year. Among the 15 areas identified, some significant differences were seen between CMOs and biologics developers.

Eric S. Langer

This year, the vast majority of CMOs, 86.2%, pointed to finding "significant" or "some" improvements as a result of single-use devices adoption, far outstripping their next most popular factor, "improved upstream production operations," at 69%. By contrast, 62.8% of product manufacturers reported "significant" or "some" improvements from single-use devices usage—a healthy percentage, but lagging behind factors such as "overall better control of process" (73.5% for biomanufacturers), "improved downstream production operations" (68.9%) and "better process development" (68.4%), among others. The data, released in BioPlan Associates' 8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, shows that implementation of single-use devices was one of the few areas where CMOs reported implementing more performance improvements than product manufacturers.

UNITED STATES VERSUS EUROPE

In comparing responses from manufacturers in the US, Western Europe, and the rest of the world (ROW), single-use device adoption was one of the major areas with divergent responses, with more in Europe than the US and ROW reporting improvements from this area. Specifically, 79.2% of Western European respondents signaled improvements derived from single-use devices, second only to "overall better control of process," at 82.8% of European biomanufacturers. By contrast, 62.3% of US respondents and 55.2% of ROW respondents reported improvements from single-use technologies, behind other factors such as improved production operations (upstream and downstream), and process control enhancements. The Europeans' preference for single-use technologies may reflect their customer purchases and/or vendor marketing catching up with those in the US, while much of the ROW still may not be heavily implementing single-use systems, or vendors are simply not yet marketing heavily in these regions.

Figure 1: Select factors in biomanufacturing performance creating "significant" or "some" improvements identified by biomanufacturers versus CMOs. (ALL FIGURES ARE COURTESY OF THE AUTHOR)

Taken together, 65.5% of biomanufacturing and CMO respondents pointed to benefits from usage of single-use devices this year, a slight decrease from the 67.2% in 2010 (2). Indeed, this year, reported improvements from single-use devices dropped to fourth on our list of factors, from second last year. This year, as in 2010, "overall better control of process" was the leading factor creating performance improvements, with 72.6% of respondents (compared with 74.2% in 2010).

WHERE HAVE SINGLE-USE SYSTEMS PROVED BENEFICIAL?

BioPlan evaluated 15 activities manufacturing organizations have implemented over the past year to specifically speed drug-development timelines. The use of more disposables and single-use devices in manufacturing took the top slot, with 40.8% of respondents. Following disposables was the use of more "platform'" downstream processes, at 37.7%. Analysis of those activities showed that there was a cluster of mid-level activities that sped drug-delivery times. These included activities such as using "platform" cell lines, improved in-process monitoring, use of "design of experiment" methods, and use of better chromatography resins. At the bottom of the attributes was "use of different expression systems." However, because expression systems are typically a one time decision, this is not unexpected.

Figure 2: Select activities implemented to speed drug development timelines identified by biomanufacturers versus CMOs.

Comparing biomanufacturers to CMOs, BioPlan found that for CMOs the number one activity implemented to speed drug development timelines was the use of more disposables and single-use devices in manufacturing (72% vs. 42% for biomanufacturers).

Trends in the time required for product development and approval are closely related to productivity and cost concerns. This year, the survey showed that acceptance of single-use devices is also being used as a cost-cutting action. Of 212 respondents to this question, 35.4% accepted single-use (disposable) systems into clinical manufacturing operations to cut costs, while 19.3% accepted single-use systems into commercial manufacturing operations for the same reason.

Survey methodology

PRIMARY REASONS FOR INCREASING USE OF DISPOSABLES

BioPlan identified reasons for the increasing trend towards use of disposable and single-use system components. Single use disposable systems can provide cost savings, and sometimes these savings can be substantial compared with fixed stainless steel systems, particularly with regard to larger systems. Indeed, as shown above, biomanufacturers are accepting single-use systems as a cost-cutting mechanism, and according to BioPlan's data, almost 58% of respondents indicate that using disposables to lower annual costs is a "very important" attribute.

However, as in previous years, direct cost reductions do not appear to be among the most widespread ("important" or "very important") factors to these decision-makers. As in earlier years, the data indicate that disposable systems users are more concerned about factors that will save time, reduce risks, and accelerate campaign turnaround. Increasingly, they are also interested in reducing capital equipment.

The primary reasons biopharmaceutical developers and CMOs use these products are to:

• Eliminate cleaning requirements (90.2% indicating "important" or "very important")

• Reduce capital investment in facility and equipment (85%)

• Reduce time to get facility up and running (85%)

• Decrease campaign turnaround time (81.7%).

A significant shift is the focus on reducing capital investment in facility and equipment. Despite the loosening of budgetary constraints, end-users are increasingly interested in seeing how disposable systems can help them avoid capital investments in manufacturing.

ARE CRUCIAL FACTORS LEVELING OFF?

The reasons cited by biopharmaceutical manufacturers for increasing their usage of disposables shows relative consistency from past years. For example, a few years ago, "eliminating cleaning requirements" took the top position over "decreasing risk of cross-contamination," as the dominant reason for increased usage. This year, 48.5% of respondents indicated that eliminating cleaning was a "very important" reason, holding consistent over the last few years.

However, many respondents are slowly reducing the importance they are putting on individual product attributes. This reduction may reflect a maturation of this segment. As the industry becomes more aware of the attributes and benefits of disposable usage, and as the use of disposables increases, decision-makers' needs and specific reasons for increasing usage continue to level out. For example, when considering all users, "Decreasing risk of cross-contamination" as a "very important" reason saw a decrease this year to 42.4% (down from 50% last year) of users. Much of this stabilization may be the result of greater experience and awareness of these devices.

WHERE DEVELOPERS AND CMOS DIFFER

BioPlan found new distinct perceptions between CMO and biotherapeutic developers when measuring their top reasons for increased use of disposables. According to Dr. Abdul Wajid, senior director of process sciences at XOMA (US) LLC, "Significant differences with biotherapeutic developers reflects CMO business model which has multiple projects pipeline, generic quality documentations enabling them to achieve faster turn around resulting in higher productivity and better use of plant time to maintain business edge," (1).

CMOs in particular can save on facility or campaign costs, which can also reduce operating costs and capital investments. The flexibility and quick turn-around times between process runs can also improve efficiency, which can reduce costs. These savings can be passed on to the client. This is the result of the CMO being able to perform different processes within the same facility. CMOs often use disposables to reduce risks of cross-contamination between campaigns, and are motivated by the need to get a facility or project up and running quickly. By contrast, biotherapeutic manufacturers tend to be more motivated by the need to keep maintenance costs low. If suppliers or associated standard-setting bodies are able develop methods for standardizing disposables, it would enable the use of secondary vendors, which is an increasingly important factor today.

"Very important" reasons for increased use of disposables that are much more applicable for biotherapeutic developers:

• Reduce time to get a facility up and running (44.6% of developers vs. 34.6% of CMOs)

• Reduce water requirements (25% of developers vs. 8% of CMOs)

• Lower annual maintenance (22.2% of developers vs. 12% of CMOs).

"Very important" reasons that are more applicable for CMOs:

• Decrease risk of product cross-contamination (56.0% of CMOs, 39.4% of developers)

• Reduce space requirements (36% of CMOs, 19.7% of developers)

• Faster turnaround time (40% of CMOs, 33.1% of developers).

These crucial reasons are reflected by the recent expansion of the CMC Biologics facility in Copenhagen to include a 2000 L single-use bioreactor. According to Gustavo Mahler, chief operations officer at CMC, the advantages are clear: "Reduced project times, reduced risk of cross-contamination resulting in increased process reliability, and reduced batch manufacturing costs that will allow CMC Biologics to be even more competitive," he says (3).

SUMMARY

There are many recognized benefits from the use of disposables, many of which can shorten lead-time to get a facility or campaign up and running. CMOs can be the first to reap these advantages, but all biomanufacturers have seen benefits. The top five reasons most commonly cited by all respondents as "most critical" include:

1. Reduce capital investment in facility and equipment (21% for 2011, up from 14.4% in 2009)

2. Eliminate cleaning requirements (12.6%)

3. Faster campaign turnaround (11.2%, up from 6.9% in 2009)

4. Decrease risk of product cross-contamination (8.4%)

5. Reduce time to get facility up and running (6.3%).

It is clear that single-use devices continue to gain acceptance in the industry, and that their benefits are being increasingly noticed. Over time, we expect biomanufacturers and CMOs to integrate disposables into most processes, especially as downstream single-use solutions and specific devices such as probes and sensors continue to evolve. In addition, as new regions such as China and India gain prominence and begin to produce biologics and biogenerics, the need for consistent quality will likely dictate the greater use of disposables, because they can often be implemented more efficiently and with fewer risks of quality problems (4). As new biomanufacturers enter the industry and new products enter the pipeline, the disposables option will become part of the decision process from the very start.

Eric S. Langer is president and managing partner at BioPlan Associates and a member of BioPharm International's editorial advisory board. elanger@bioplanassociates.com.

REFERENCES

1. BioPlan Associates, "8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production: A Survey of Biotherapeutic Developers and Contract Manufacturing Organizations" (April 2011).

2. BioPlan Associates, "7th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production: Survey of Biotherapeutic Developers and Contract Manufacturing Organizations" (April 2010).

3. CMC Biologics, "CMC Biologics Adds 2,000 Liter Single-Use Bioreactor at its Copenhagen Manufacturing Facility," press release, (Copenhagen, Denmark, Sept. 1, 2011).

4. BioPlan's Top 1000 Global Biopharmaceutical Facilities Index, www.top1000bio.com/index.asp, accessed Aug. 20, 2011