What are the key hurdles to overcome in adopting single-use processing?
Dr. Jenkins: Managing bag inventories can be challenging. A greater focus is needed throughout our supply chain. Sourcing and quality need to re-align to handle the change in manufacturing strategy. Auditing and partnership with our suppliers is a crucial function in ensuring quality and supply. Hence, supplier selection becomes significant in the overall single-use strategy. Vendors have satisfactorily addressed such issues as leakage, extractables, and leachables.
Matthews: The major hurdles are the investment cost in existing infrastructure, and the characterization of extractables and leachables. Also important are status quo (general fear of change) and supply chain security.
Manufacturers are concerned whether disposables are truly capable of replicating validated processes in disposable format. This relates to material of construction changes, and the ability to reproduce process control inside of the customer’s characterized and validated operating limits, especially pertaining to critical process parameters.
Munk: We believe the regulatory concerns to be the dominant hurdle industry-wide. The lack of experience by the regulators makes it difficult to address the most important risks, both real and perceived.
Furthermore, suppliers must realize that the end-users are actually outsourcing part of their quality system to them. Thus, the suppliers have to prepare for more audits, for which they must demonstrate GMP-compliant quality systems, including CAPA systems, change control, etc.
Additionally, how suppliers control their raw materials is of great concern, as changes in raw materials might lead to changes in extractables and leachables, which could affect process performance (for example cell growth) or the patient risk profile.
Dr. Runser: Routine use of today’s available disposable solutions still requires a lot of manual handling by well-trained operators, which limits single-use equipment in high-throughput facilities.
The risk of failure, caused either by material deficiency or by operator errors, is still higher compared to standard stainless steel systems. Therefore, the use of disposable systems in a large-scale facility is still preferred for process-supporting activities such as buffer and media storage, rather than for usage of product-containing solutions.
Dedicated disposable solutions still require a long lead time before first use in a GMP environment. In addition, dedicated bag configurations can show more deficiencies than off-the-shelf products. Novartis and its partners have worked to improve inspection and handling procedures to assure a smooth use of disposables in our large-scale manufacturing facility.
Dr. Schlatter: Second supplier concepts are one key challenge: the systems of different manufacturers need to become interchangeable. Regulatory acceptance and experience with the equipment are additional hurdles.
VonEsch: The biggest hurdle to overcome is legacy equipment, and the fact that drug and equipment manufacturers tend to push and develop what they know. Once vendors and manufacturers adopt these technologies and offer simpler implementations, they will grow.
There are five key components to adopting single-use equipment: educated drug companies, educated equipment vendors, educated disposable manufacturers, educated building design/engineer firms, and lastly regulatory oversight buy-in.
Today we have a mix of these components. But wider adoption of single-use will require that stakeholders understand the favorable applications in all aspects of drug manufacturing.
I would say that the smaller drug manufacturers are driving most of these efforts currently, companies that understand the costs, benefits, and flexibility of not just the systems but the manufacturing plants as a whole once these systems are in use.
Dr. Witcher: The reliability of single-use systems is of concern. The possibility of leaks and broken bags are perceived to be a problem. In addition, the ability to get special single-use items from vendors is also a concern.