Ten Years Later: Innovation Driving Single-Use Technology Advances

Ten years ago, single-use systems were an emerging technology moving from common use as storage bags for cell culture media and serum, into broader applications that have developed into a major trend in clinical biopharmaceutical manufacturing. Advances continue as more robust, better designed, and standardized technologies, with more inert materials, are developed for GMP applications. As single-use/disposable bioprocessing moves toward commercial-scale manufacturing applications, even more innovation is being demanded by the industry.

PHOTO CREDIT: ISTOCKPHOTO/GETTY IMAGES

In BioPlan's 10th annual report on the industry, four of the top 21 new product areas being sought by this industry were single-use related: disposable bags and connectors topped the list again this year, with 44% of the industry demanding better technology/products (compared with 40% last year), following were probes and sensors (39.6% this year, vs 34% in 2012) (1). In comparison, stainless equipment once again hit the bottom of the list, with fewer than 5% indicating they would like new products developed in this area (see Figure 1). The reason for this interest is partly because single-use devices allow lower overall facility costs, reduce contamination problems, provide faster changeovers, and reduce shutdown times. As such, they continue to grab the focus of the industry.

Figure 1: Selected new technology and innovation areas demanded by the biopharmaceutical industry (a few of the 21 key areas indicated).

In fact, a separate BioPlan study conducted in late 2012 of the 450 global subject matter experts and senior industry participants who make up BioPlan's Biotechnology Industry Council (BIC), asked participants to identify the key trends and factors they see in the industry. This year 22% of senior industry decision-makers pointed to single-use devices as a key trend, just behind downstream processing (24%) and analytical methods (24%) (2).

While single-use devices remain a hot topic this year, much has changed from when they were first being evaluated by the industry. BioPlan's biomanufacturing industry study includes trends in the use of disposables and single-use systems. Data over a multi-year period offers insights into how the market for single-use equipment has evolved over time, and where it may be headed.

CURRENT USE OF DISPOSABLES

BioPlan's 10th Annual Report indicates that adoption of single-use devices has continued to increase, and that some disposable devices are now almost universally used at one stage of bioproduction (R&D through commercial production) (1). When compared to adoption just seven years ago, the growth has been significant.

Topping the list in market adoption this year are disposable filter cartridges, now used by 98% of respondents to the latest survey, up from a leading 93% last year, and 78% in 2006. The growth has been even more dramatic in other widespread devices:

• Tubing for disposable appli-cations (97% this year, up from 88% last year and 56% in 2006)

• Buffer containers (91% this year, up from 82% last year and 53% in 2006)

• Depth filters (90% this year, up from 84% last year and 57% in 2006).

Even some of the lesser-adopted systems are showing strong growth. For example, this year, membrane adsorbers, the devices with the least amount of penetration, are still being used by 6 in 10 respondents (61%), up from 54% last year and just 13% in 2006. For many of the devices tracked, there was a big jump in adoption between 2006 and 2007, with growth rates slower since then; nevertheless, these trend figures show just how quickly the market for these devices has grown.

It is also worth noting that quantities for these products were not indicated in the survey question, only incidence of usage at any stage. Thus, while market penetration and the number of purchasers for these products may be increasing substantially, these data do not provide direct information on the volume of sales increases. Separately, though, vendors have reported double-digit sales growth in materials and consumables for several years, most likely attributable to the increased adoption of single-use disposables and the introduction of new products in this sector of the market.

WHY INCREASED USE OF DISPOSABLES?

While there have been dramatic changes in the adoption of disposable devices, some trends have remained remarkably steady over the years. BioPlan identified a series of more than 25 reasons for increasing use of disposables and asked respondents to indicate their single most crucial reason—fully 26.1% cited reduced capital investment in facility and equipment. This has been the top reason going back at least as far as 2009, increasing from 14.4% of respondents that year. Clearly, this has been one of the key benefits of single-use devices, and has become more important over time.

This year, "eliminate cleaning requirements," cited by 13.6% of respondents, was the second-most crucial reason for increasing use of disposables, as it has also been since 2009. The percentage citing this factor has remained steady over the years. In a tie for third place this year, each at 9.1% of respondents, were "faster campaign turnaround time" and "flexibility of a 'modular' approach." The former retains its third position from 2010–2012, though has leveled off after rising growing steadily from 6.9% of respondents in 2009 to 12.4% last year. The latter appears to have grown more important, after ranging from 4.2-6.3% of respondents for the past four years.

FACTORS RESTRICTING GREATER ADOPTION OF DISPOSABLES

While maturing, introduction of single-use, disposable systems is still relatively new, and as such, the number of factors decision-makers recognize as hurdles continues to evolve. While the market has burgeoned, there are some challenges that the industry still needs to overcome before the next stage of penetration can be reached. And in this area, we see some interesting trends.

This year, when industry personnel were asked their single most important reason for not increasing use of disposables, of the 23 potential reasons identified, 1 in 5 respondents focused on one: leachables and extractables. Concern regarding leachables and extractables has grown steadily in the past few years, doubling from 10.4% of respondents in 2009.

As recently as 2011, this was not the top concern hindering adoption. Instead, the most common reply from respondents was that they had already invested in equipment for their current system, hindering further use of disposables. Over the years, however, that reason has gradually become less of an issue, perhaps as current installed equipment has depreciated or worn out. There was a slight rebound in the percentage of respondents indicating this reason to be their primary concern this year (from 13.3% to 16.3%), but that this factor remains less of a worry today than leachables and extractables.

Other trends seen include the declining proportion of respondents saying that the high cost of disposables (consumables) is their top hindrance—as can be expected with greater maturation of the market—and a general increase in the proportion who are concerned with not becoming vendor-dependent (single-source issues).

DEMAND FOR INNOVATION REMAINS HEALTHY

One reason why the disposables market has been able to overcome the above obstacles is the continued pace of innovation in this area. Each year BioPlan asks the industry to identify the top five areas they want their suppliers to focus their development efforts on. And seemingly with every passing year, the industry responds that they want innovation in disposable products.

As mentioned above, this year, a leading 43.8% of respondents indicated that disposable products, bags, and connectors are an area of interest, up from 40% last year and 36.5% the previous year. Interest in having suppliers improve their single-use devices is an indication of broader general adoption and a greater number of potential applications that are not being met with current technologies. Some of these concerns include the need for:

• Better materials with fewer particulates, and lower leachables and extractables

• Stronger, more robust materials, tubing, films

• Products able to withstand freeze/thaw cycles

• Better probes and sensors to meet more varied applications

Suppliers generally have been answering the call: past surveys have indicated that disposable bioreactor bags/consumables, single-use bags/films, and disposable chromatography have consistently been among the top new technologies or product development areas suppliers have said their organizations are working on, and expending R&D resources to resolve.

LOOKING FORWARD

The industry sees great promise in the continued adoption of disposable devices. Entirely disposable upstream processes that can support large, commercial-scale production are becoming a reality, and now companies are focusing on cost-effective downstream single-use innovations. Today, even the older, more conventionally built facilities are looking to modify their infrastructure to support disposables for production. Over time, conventional processing equipment, in part or as integrated into overall process trains and modules, will be replaced by disposable designs or established as hybrid production modules.

The future of innovation within disposables areas is likely to bring about an array of advances. These will be driven by many important sub-trends that continue to shape this market. Industry experts from our BIC panel identified numerous such trends, including:

• Building quality into single-use operations to further reduce regulatory activities and oversight

• Fixing disposable bioreactors that are creating inconsistent growth due to changes in resins, films, gamma irradiation, and cell-line specificity

• The emergence of flexible and modular biomanufacturing facilities that reduce the need for expensive, stand-alone facilities for every drug product

• Single-use devices facilitating large-scale bioproduction in developing regions

• Leachables and extractables standardization at clinical and commercial scale

• More new, scalable devices for downstream processing that get away from existing labor-intensive, costly technologies.

Although, as yet, there are few, if any non-rigid single-use devices (e.g., bioreactor bag liners) used in GMP applications, this will likely change quickly as new products move through the development pipeline, into clinical-scale manufacturing, and on to regulatory approval for commercial GMP production. Leachables and extractables will remain a concern, but as data are developed and experience accumulates, the worries will diminish. The more vendors collaboratively work with customers, the greater the likelihood that disposable, single-use products will deliver sooner on their promise to change bioprocessing for the better.

Further, as regulators gain familiarity with the safety profiles and materials used in these devices, necessary approvals for product manufacture will be facilitated. When this occurs, the market volume for single-use devices is likely to increase significantly.

ERIC S. LANGER is president and managing partner at BioPlan Associates, Inc., a biotechnology and life sciences marketing research and publishing firm in Rockville, MD, elanger@bioplanassociates.com

REFERENCES

1. BioPlan Associates, 10th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production (Rockville, MD, April 2013).

2. BioPlan Associates, BioPlan Associates' 2013 Biotechnology Industry Council Trends Analysis Study, (Rockville, MD, December 2012).