User Viewpoints on Disposables Implementation

The industry is in transition. There is a renewed focus on cost and efficiency, and as a resilt, we are seeing a major uptake in the use of disposables technologies. The opportunities provided by disposable technologies also come with risks, however, and single-use technologies are not a homogenous toolkit that provide a simple fix. Rather, the market offers a mixture of technologies at different states of maturity from a wide variety of suppliers. This variability poses challenges in terms of supply chain and technical risk. In this article, we present the end-user perspective. Since the last column, we have visited Interphex in New York, and talked to a number of industry leaders from the manufacturing and contracting manufacturing sectors for their perspectives on the real concerns arising from the adoption of disposable technologies for the commercial manufacture of biotech products.

Miriam Monge

CHALLENGES AND OPPORTUNITIES

When we discussed the challenges and opportunities posed by disposable technologies, we asked a number of questions. Do disposables really change the way end users look at and manage operations? Do disposables technologies change the way they view and operate the factory? How can the opportunities be maximized, and the downsides be minimized?

Challenges. From these conversations, several key challenges emerged.

Cost. There are significant differences in the announced pricing from one supplier to another. Many suppliers try to play on the fact that they have a unique technology and accordingly charge a significant premium, whereas others take a pragmatic approach, thinking about long-term relationships. One interviewee said that cost does indeed matter. "The end-user may appreciate a new disposable technology for the benefits it brings in terms of simplifying equipment preparation, cleaning, etc., but will not adopt this technology if it actually works out [to be] more expensive than the technology the end-user was working with previously," he said.

Andrew Sinclair

Quality and reliability. By moving to disposables, the end user is effectively outsourcing a major part of manufacturing and quality management. As a result, the user must work very closely with the supplier to ensure that robust quality throughout the manufacturing process is maintained.

Supply chain. Supply chain risk is a common sourse of complaints related to dual sourcing and consistency of supply. One user commented that his (her) company's zero change policy requires careful planning. "We ask our disposable suppliers contractually for a guarantee of supply without change for a 5–10 year period," he (she) said. Such a policy means that the user has to consider the supply chain in most minute detail in terms of component and film suppliers and ensure that all the necessary contracts are in place.

Ergonomics. One user noted the operator's role in terms of handling of large-scale containers and the manipulation of tubing sets. "When working with disposables, there is a much greater dependence on the operators themselves. If they make a manipulation error, this could contaminate the whole process," he said. "We work with our suppliers in designing disposable systems that are as intuitive as possible, are idiot-proof, and so minimize the risk of operator error."

Opportunities. The opportunities presented by single-use technologies for manufacturing tend to relate to flexibility of operation, ease of product changeover, and the removal of wasted activities in terms of preparation and cleaning. "The great opportunity with disposables is that we can spend more time concentrating on manufacturing steps, the productive steps, and get rid of preparation work," said one interviewee. Users also see significant benefit from disposables when applied to process development, where fast turnaround in pilot and clinical supply facilities are extremely important.

DISPOSABLE TECHNOLOGY EVALUATION FACTORS TO CONSIDER

The preceding section on challenges and opportunities leads us to the evaluation process. All users have to evaluate new technologies, and disposables are no different. So what are the specific considerations? As expected, this is not a simple process and many factors must be considered. It is also important to develop a close collaboration with the supplier during the evaluation process.

Quality. The goal is to to ensure a supply of material with totally reproducible, consistent quality. How can this be achieved? End users indicated that there is still a way to go before such reproducibility is achieved. One end user indicated that during audits, his team looks carefully at the training programs put in place for the staff that manufacture the disposables systems. The level of staff turnover is also noted. "The manufacturing and assembly of disposable systems is rarely highly automated, so consistent quality can only be obtained by highly experienced manufacturing operators at the disposables manufacturing end," he (she) also explained. Of course, quality controls, over incoming raw materials and in-process, and on finished products plays an important role in ensuring reproducible quality.

Economic evaluation. Are there savings to be had at the time of implementation and over the whole product lifecycle? A business case and comparison with existing systems typically will be made. Many companies assess the total cost of ownership, and some use net present value models that integrate costs from each process step. According to one user, when looking at costs, "we integrate waste costs but we don't integrate the relative waste costs for traditional manufacturing technologies." In this instance, although the user is evaluating the increase in the solid waste costs of disposables, they do not evaluate the reductions seen in liquid wastes when moving from disposables.

Technology assessment. What is the level of maturity of the technology and the potential of risk to product?

Supply chain. As discussed above, companies place enormous emphasis on the robustness of the disposables supply chain. One interviewee from a major vaccine manufacturing company reinforced this point. "We consider [that] we are taking considerable risk [when] outsourcing many activities for our manufacturing requirements that we would have previously carried out internally," he said. As a result, his team asks many questions, such as: Is this an experienced mature supplier who has been supplying disposable technologies to the market for several years, or a total newcomer? Is there an alternative supplier for a given technology? "Certainly, our aim is to have dual sourcing for all our disposable technologies," he continues. "For existing applications, this is not always the case, because validating a second supplier represents a lot of work, so the resources need to be made available to carry out the necessary validation work." If there is only one supplier of a technology, then the end user clearly needs to carry out a very detailed supply chain evaluation.

As with any supplier, there must be regular audits and controls, and strong relationships must be built up to create trust. In terms of risk, the fact that there has been considerable consolidation among the filter and bag suppliers limits choice. Ideally, for every technology there would be the option to work with material from an alternative vendor, but that may not be possible.

Another interviewee from a major monoclonal antibody manufacturing company explained increased supply chain risk involved in disposables and how his company handled it. "In contrast to traditional reusable systems, where we have full control in terms of ongoing maintenance and so on, with disposables we are changing the scenario and have far less control," he (she) stated. "We have developed a full deviation and investigational methodology for identified defects in the disposables supply chain as this could potentially affect a large number of our products."

Evaluation process. The evaluation process typically involves a feasibility study, testing, and comparison to the traditional set-up. Depending on the complexity of the technology, the evaluation can last from a few months or up to two years. Generally, the technology will initially be implemented at pilot-scale, occasionally with the need to work with the supplier to fine-tune certain technology features and to ensure the robustness of the supplier's manufacturing, quality, and supply chain for the given technology.

There were several common issues that were experienced during this evaluation process.

First, end users often have technical questions relating to specific features of the technology (such as the agitator not working correctly, or difficulty with the aeration systems, filters, and other systems).

End users also often have questions about validation, and validation inevitably takes longer than anticipated. Users are often told that validating disposable systems is simpler than validating traditional systems, but this is not the experience of many of the end users we talked to. "The different studies that we need to carry out in terms of chemical resistance and interaction studies often take considerably longer than the equivalent studies required for traditional systems," commented one.

So what are the important criteria that must be met before any disposable technology can be adopted? They are performance, cost, and supply chain security.

WHAT'S MISSING?

Any discussion of what's missing has the implied assumption that we are trying to achieve a totally disposable process, but this is not the case. "I would not talk necessarily about gaps in the disposable technology offering—it is a more a case of where does it make sense to use disposables for a given process," said one user. "The suppliers think that they can solve everything with disposables!"

Products. There are a few gaps in component offerings, however, one common desire is for a mature disconnection system that can be used several times. Users recognize, however, that we are just at the beginning of the technology developments in this arena.

Another frequent request among end-users was a smaller-scale version of the single-use stirred tank bioreactor. End users asked that such systems be made available in the 10- and 20-L format.

Services. It is apparent from the feedback that there is some level of dissatisfaction on the service front, with some end-users demanding:

• Disposables suppliers guaranteeing a no-change policy for a 10-year period.

• More collaboration between suppliers, leading toward greater standardization of films, containers for bags, and components used in systems.

As the disposables market matures, there is also a requirement that the disposables suppliers think about the longer-term requirements of the industry rather than trying to impose single-source dependency.

Indeed, the way in which the disposables suppliers approach the market suggests that different companies and technologies are at different stages of maturity. The disposables suppliers who have been supplying the industry for many years have reached a level of maturity that allows them to approach the market thinking about the requirements for industrial implementation, whereas the suppliers who have arrived on the market more recently are still approaching the market from an innovators or early adopter point of view by considering only the technical issues without considering the users' requirements from a business perspective for things such as consistent quality and supply chain security.

If a larger number of disposables suppliers were able to reach the required level of maturity, the end-users we talked to believe that this would enable a far greater deployment of disposable systems because the risk the end users are taking would be diminished. As one user said, "Our company has quite frequently walked away from certain disposables implementations due to the lack of maturity of the supply chain and lack of availability of dual sourcing."

ENVIRONMENTAL MATTERS

It is apparent that many companies are concerned about environmental issues. This in part is being driven both by good stewardship and by legislation. Many of the companies we have talked to have internal initiatives to reduce their carbon footprint. However, there is always a question of the methodology used to determine where to start and where to finish when comparing stainless and disposables. Again, one user illustrates a fairly typical viewpoint. "We do have an internal initiative around environmental and operational sustainability," he said. "We also talk about the concept of green procurement ... the article, 'The Environmental Impact of Disposable Technologies: Can Disposables Reduce Your Facility's Environmental Footprint?' has been widely read in our organization and has generated considerable internal discussion."¹

SUMMARY

With increasing titers opening up, the opportunity to work with smaller-scale processes, the need for highly flexible facilities, and the need to drive out costs in biomanufacturing by a factor of ten, there is a huge potential in the future for much broader disposables implementation in biomanufacturing. The suppliers will have to listen and respond to industry requirements, however. If they don't, the uptake of disposables in commercial operations will be limited.

Discussions and interviews that the authors carried out with experienced industry end-users, however, highlight a number of these requirements in which end-users would like to see the disposables suppliers mature to build the level of confidence required for a much broader implementation of these technologies.

• Mature commercial positioning in relation to cost management

• Adoption of an industrial approach to disposables implementation as opposed to a niche approach. This links into the request by end users for technology standardization and more openness among the suppliers to work together to enable the requirement for dual sourcing.

• Better understanding of the relative costs of disposables versus traditional systems throughout the product lifecycle

• Reproducible quality

• Robust supply chain with no-change guarantees for a 10-year time frame

• Designing intuitive disposable systems that minimize the risk of operator error through clever design.

ACKNOWLEDGEMENTS

In preparation for this article, we talked to a wide range of users. We would like to thank all those individuals for giving up their time to talk to us. In particular, we would like to thank the two industry experts we interviewed who are actively leading teams carrying out disposable system evaluation and implementation. One is the head of enabling technology for a major monoclonal antibody manufacturer, and the other is the head of disposable technology implementation for a major vaccine manufacturer.

Andrew Sinclair is the managing director and Miriam Monge is the vice president of marketing and disposables implementation, both at Biopharm Services, Chesham, Bucks, UK, +44 1494 793 243, disposables@biopharmservices.com Monge is also the European chair of ISPE's Community of Practice for Disposable Technologies.

REFERENCES

1. Sinclair A, Leveen L, Monge M, Lim J, Cox S. The environmental impact of disposable technologies. Supp to BioPharm Int. 2008 Nov;4–15.