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Reduced carryover risk and close attention to particulate control result in greater patient safety through the use of single-use systems.
What started off more than a decade ago as a cutting-edge technology has now become mainstream; the arguments in favor of biopharmaceutical production using single-use equipment have largely been proven. There is an understanding that financial considerations are no longer a deterrent for adopting disposables, but more importantly, there is another realization concerning the use of single-use technologies. The industry has started to look beyond the immediate manufacturing implications and into how these technologies benefit end users (i.e., patients) through increased product visibility, better product quality, and patient safety.
Patient safety is the most important topic of discussion in the biopharmaceutical industry today, and rightly so. Manufacturing companies are focused on finding ways to ensure that any accompanying risks are reduced to save patients from unnecessary risks to their health. Secondarily, manufacturers want to ensure that they are not losing batches because of contamination, which means lost money.
But what does all of this really mean? Here we look into how single-use technology continues to offer new levels of performance to the industry and how it can benefit the patient.
Although the economic model for using single-use technologies includes various benefits, the intangible benefit of increased patient safety has emerged and started a trend in the vast majority of multiproduct facilities. Many manufacturers are finding ways to implement single-use technologies into their process because patient safety, by way of avoiding cross-contamination, should trump cost savings.
While the adoption of single-use technology has made great strides, it is often true that a single-use-only facility may not meet all the needs of drug manufacturers, nor is it always feasible. Mixed needs, therefore, have spurred a trend towards multi-use hybrid or flexible facilities, which combine the proven benefits of traditional stainless-steel and glass equipment with the promise of single-use equipment. The key is finding the right balance to fully maximize the potential of the facility by reducing validations, water use, and operator risk, and increasing productivity. The most attention should be paid to how to introduce these flexible facilities in a way that greatly reduces (with the ultimate goal of eliminating) cross-contamination potential between successive product batches.
The increasing potency of new medicines has further exacerbated the need to know what contamination risks are present. There are many new products that require only minuscule amounts of contaminants to cause a strong pharmacological reaction in patients. This potency is advantageous in dosing terms—maybe the dose will be one pill instead of three, or a biologic might need to be injected once a month rather than once a week. However, on the manufacturing side, it presents a new cause for concern. While a residual nanogram of aspirin may have no physiological effect, a microgram of a monoclonal antibody very well might have an effect that could be extremely harmful to the patient.
For a manufacturer reliant on fixed stainless-steel vessels, there is always a risk that minute quantities of product will be left behind to contaminate the next batch, regardless of how carefully a vessel is cleaned. As drugs become more potent, the safe limits for residual product carryover become ever more challenging to achieve. Single-use equipment eliminates the potential for cross-contamination almost completely, because the process vessels are thrown away after use.
When introducing single-use equipment, users—to their credit—are keen to monitor all manner of parameters they would not necessarily contemplate studying for a stainless-steel system. Particulates, extractables, and leachables all come under examination with single-use systems.
The concern lies in making sure the product does not become adulterated during its manufacture. The vessels hosting production are made from plastic, so there is always the potential for extractables or leachables to find their way into the product from or through the film, or for gas permeation through the walls of the vessel. It's the same story in the final packaging because extractables, leachables, and gas permeation are all potential problems with plastic vials. And in general, particulates are a concern; they can either come from the equipment itself or from the atmosphere around the systems.
In the past, a final product was inspected for particulate contamination—first by eye and later, as automated systems became available, by machine. Often, any particulates found in traditional systems were not given much attention; they were either not large enough for concern or there was not the right technology to isolate their source. Single-use products change this level of scrutiny because there is suddenly better product visibility. Suppliers are expected, and are now able, to tell manufacturers what particles might be present and where they potentially came from.
This added material tracing and product-tracking capability brings an unexpected benefit of product quality and, thus, provides a patient safety benefit. Because the process is better studied, more traceable and more defined, the quality bar is automatically raised. The product-contact surfaces are better understood because they have been investigated in detail, and the validation process now generates more data than ever before.
Biopharma producers rely on their suppliers much more than they have in the past. For a single-use-only facility, the suppliers are the new product, and often process, experts. Moreover, they essentially control the factory; if the bag and vessel suppliers ever cannot deliver, production could cease. All this reliance has created demand for greater support, supply-chain contingencies, and documentation than ever before. Companies that take advantage of single-use technologies are doing so because of the various benefits they offer. Undoubtedly, single-use technologies have allowed these companies to identify new ways to ensure quality of end product for patients.
Single-use suppliers are working hard to characterize anything—particle or otherwise—that might be present, and identify if it originates from the bag, the tubing, or a fitting. The elimination of particulates has been a recent driver for the industry. Customers want to know whether the particles are native (i.e., originating from the single-use system) or foreign, such as from a piece of paper in the cleanroom. Ultimately, customers want suppliers to ensure that particles are eliminated.
Being able to detect and quantify particles is the first step, and the next step in improving product quality is to eliminate them. Each step brings us closer to the vision of better protecting patients and ensuring the drug products they ingest have the intended effect, with no adverse risk factors from preventable causes.
Eric Isberg is global product manager, Integrity single-use fluid technologies, at ATMI, firstname.lastname@example.org.