On several occasions, I was asked during a panel session that included discussions about disposable versus stainless steel technology, “Which technology is best for today’s drug product manufacturing.” In answering this question, I am reminded of the quote by the American ambassador and diplomat Chester Bowles who rightly said, “When you approach a problem, strip yourself of preconceived opinions and prejudice, assemble and learn the facts of the situation, make the decision which seems to you to be the most honest, and then stick to it.”

The choice of disposable technology versus stainless steel is such a decision, and one that has become even more common over the last few years within the (bio)pharmaceutical industry given the rapid increase in use of disposable equipment. And, though we do not see disposable equipment replacing traditional multi-use stainless steel in the fill and finish industry, there are a few distinct areas within the manufacturing workflow where this technology can be seen as a promising alternative. This is why a number of process steps in pharmaceutical manufacturing are increasingly moving toward disposable technology approaches; to enhance operational flexibility and to reduce capital investments in equipment.

The reasons for both technologies are many, and therefore, well worth the time to consider the merits of each, examining how they compare and differ, before making any final decision. But before going too far in our comparison of technologies, let us agree on the one guideline that has broad consensus in its application to disposable technology: it is especially suitable when drug substances come into direct contact with equipment. This includes API and excipient weighing, material preparation, compounding and filtration, as well as the core area, meaning the filling process itself, among others. Looking at two of these central examples, disposable equipment for compounding needs often can be sourced and processed in a straightforward manner. However, the situation with disposable filling equipment is more complex due to the high cleanroom requirements to avoid microbiological contamination. In such cases, more complex equipment sterilization procedures are necessary for bringing the material into the cleanroom. 

Let us now turn to some of the key parameters to consider in making a decision between these two very different, but commonly used technologies.

Time is money
This adage well applies to the choice of technology. To demonstrate, we need to look at how parameters such as procurement time or possibly needed cleaning validation time can differ between stainless steel and disposable equipment.

With stainless steel the timeframe needed before filling begins with purchasing time and initial equipment qualification. These times can vary anywhere from four to twelve months. Additionally, the aspect of cleaning validation time, which can also vary from one to three months, must be factored in as well. Combined, this brings the time needed before initial batch filling anywhere from five to fifteen months. Additionally, we must take into consideration the requalification of cleaning equipment, including its procedure. This can add an additional one to three months.

By contrast, disposable equipment, in the best case scenario, requires a purchase time of only a few weeks. However, production and delivery cycles for pre-manufactured and pre-sterilized equipment may also take several months and can be quite complex, the same as with the supplier processes themselves. And there can be a dependence on single suppliers due to a lack of alternative sourcing options.

Overall, the time differences between these two technologies can at times result in real savings. We can, of course, only approximate what those figures are as based on internal calculations with various sample projects. The individual schedule will, of course, depend on the drug itself, the complexity of the necessary equipment, and other key criteria.

Costs and yield can vary significantly
We can also compare these two technologies by looking at the investment costs associated between them. Today’s price for stainless steel fill and finish equipment such as tanks and needles, often range from $100,000 up to $500,000 for more complex systems. These figures depend on the drug, the complexity of the equipment and other factors. Such costs are challenging, particularly for smaller companies in the early drug development process that often have very tight budgets and significant uncertainties about their overall drug program. By comparison costs for disposable equipment range from approximately $5,000 per 1,000 unit batch, with costs increasing as batch size increases. Additionally, the acquisition costs for disposables can vary substantially depending on the kind of components used and the manufacturers. Also, the used disposables generate high destruction costs as they are considered hazardous waste. We cannot forget other areas that have to be taken into consideration in detail such as supply chain management subjects like time-limited and cost-intensive storage possibilities as well as the challenges associated with defining minimum stock numbers.

API, the very drug substance itself, is clearly the most valuable asset of a company. It is not uncommon for an amount of API as little as 500ml to have a value of $500,000 dollars or more. Thus, it is critical to efficiently use as much API as possible. Any non-output delivering processes that utilize valuable API, such as for cleaning validation studies, are unfavorable to sponsor companies. In the early development phase when using stainless steel equipment, we find that the API necessary for performing the cleaning study in some cases can be nearly the full amount created in this phase. This is difficult to communicate to drug companies who obviously want to use their valuable API for the clinical study itself, not for equipment validation studies.

However, we must remember that the quality of delivered disposables equipment can also vary, sometimes significantly. In the worst case scenario it can create the risk of API loss due to poor equipment quality. Therefore, it is crucial that the equipment meets with appropriate pharmaceutical quality as it pertains to the product itself and its accompanying processes.

Flexibility is another key
Early in the drug development process, flexibility is one of, or perhaps the primary success factor. In times when information about the final drug product itself is limited, and there is a need to make quick decisions regarding processes and other adjustments, the use of stainless steel often falls short of being the ideal option, especially when taking into consideration the high fixed costs and relatively long delivery time. In the worst case scenario, by the time of the first use of stainless steel equipment, major manufacturing parameters may have changed, resulting in the equipment to be either outdated or unnecessary.

A drug’s characteristics can significantly affect technology
Additional main influencers in selecting the right technology are the individual project and product characteristics, as well as process requirements.
On the project side it begins with parameters such as batch size and compounding volume, the number of needed batches in project phase as well as the batches expected in commercial phase.

Selected influencing factors resulting from the product and process side include choosing the right equipment to meet with the products’ light and oxygen sensitivity and the products cooling needs in compounding stage, as well as any special requirements for its mixing and stirring.

Additional risks exist regarding extractables and leachables, arising from the components of disposable systems, and owing to potential effects on final quality and safety of the drug product. This impact has to be fully verified in a detailed manner before applying disposable technology.

At the end of the day, having options should never be thought of as a negative situation for sponsors. Both technologies have their pros and cons. And, from the point of view as a manufacturer, we appreciate the fact that these options exist for us to offer our customers. As with other businesses, there rarely exists a “one size fits all” solution. That is why every sponsor, together with its suppliers throughout the supply chain, has to look for the best solution in their particular situation in order to achieve a safe, flexible, and fast manufacturing process.

This pragmatic and insightful approach is not unlike like that suggested by Chester Bowles, and a method that makes decision making simpler and far more effective. 

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Dr. Claus Feussner is senior vice president of Vetter Development Service, responsible for the company’s development centers in both Ravensburg and Chicago. Dr. Feussner’s responsibilities encompass the divisions of manufacturing sciences and process development, technology and process transfer, project and service analytics, drug delivery systems, as well as the newly created department of innovation management.