To fast-track time to market and gain a competitive edge, pharmaceutical and medtech development companies are increasingly implementing single-use technologies (SUTs). SUTs also serve to improve patient care by decreasing the potential for healthcare-associated infections (HAIs).
The U.S. Food and Drug Administration defines a single-use device as follows: A single-use device, also referred to as a disposable device, intended for use on one patient during a single procedure. It is not intended to be reprocessed (cleaned, disinfected/sterilized) and used on another patient. The labeling may or may not identify the device as single use or disposable and does not include instructions for reprocessing.
SUTs are built using an array of components, including sampling bottles, tubing, filters, clamps, check valves, sterile connectors, Luer locks and fittings, seals and gaskets, and dispensing tips/nozzles. The technology can be as simple as a single assembly, or an entire system made up of multiple complex assemblies that are utilized across the entire manufacturing process including formulation, upstream/downstream processing, and final product filling.
SUTs offer many benefits compared to traditional stainless-steel systems. When a product is developed for single use, it eliminates the need for clean-in-place or steam-in-place (CIP/SIP) requirements, it enables faster changeovers between batches resulting in reduced production time, and it provides for a more flexible infrastructure and a decreased risk of cross-contamination.
Although standard, off-the-shelf SUT assemblies are currently available, most are narrowly focused on upstream processes using kit components like bottles, tubing, connectors, and filters likely supporting research applications. There are, however, a few companies leading the innovation of single-use systems for fill/finish. In addition, novel biologics and synthetic compounds often have unique manufacturing processes that require custom assemblies that are more advanced than standard off-the-shelf options.
Given the increasing adoption of single-use technology for both small and large molecule drug development, outsourcing the design, development, production, and validation of the SUT assemblies and systems can help speed time to market.
Invest up Front and Focus on the Science
Outsourcing enables companies can keep its scientists and engineers focused solely on new product development. As product development progresses, scientists should not be spending their time designing and putting together bottles, caps, and tubing system, but instead maintain focus on the product itself. Unfortunately, off-the-shelf components may not meet the requirements because single-use systems are comprised of various components. These components can quickly become a complex system that requires expertise in choice of materials, biocompatibility, connection strength and integrity. An expert partner can integrate phase appropriate manufacturing solutions to enables medtech companies to focus on the science and new product development.
Develop SUT in Parallel with Drug Product
As a product moves out of R&D into clinical trials and then into commercial manufacturing, the requirements become more stringent and the SUT development should build concurrently. This type of approach focuses on specific requirements at each phase rather than a one-size-fits-all approach.
Phase appropriate implementation of SUT into the manufacturing process can be integral to accelerating the speed to market. When small batches of product are being manufactured at the bench, the focus is on consistency and repeatability to increase the likelihood of successful scale-up.
As a product progresses from the bench into clinical trials, the next phase of SUT development entails conducting validation studies and providing documentation that can support the customer's investigational new drug application or 510(k) as required by the FDA. Good manufacturing practices (GMPs) ensure proper design, monitoring, and control of manufacturing processes and facilities. This includes establishing quality management systems, obtaining appropriate quality raw materials, detecting product quality deviations, and collaborating with third party, accredited testing laboratories for method feasibility and validation studies.
Rather than investing the time required for the design and management of validation studies, an SUT supplier can aid in risk-based solutions and manage the project directly with the lab. Because SUT assemblies are typically custom designs with unique components, the validation process is considerably more complex than in the past.
SUTs require identifying components, qualifying suppliers, and developing or modifying methods of assembly with leak testing, as required. They often require complex tubing sets spanning formulation to fill in pharmaceutical packaging facilities. Custom single-use assemblies can include automated biopharma product transfer, sampling, fill/finish, and other biopharma-grade tubing and hose assembly requirements.
To facilitate the transition from R&D to commercial manufacturing and increase speed to market, OEMs or their outsourcing partner must ensure that they have an established supply chain of research and GMP compliant components and a design library of proven, leak proof connection. It is also essential to have validated manufacturing, assembly, testing and packaging processes, as well as a registered quality management system.
Additionally, if a component is not commercially available, it may be necessary to design and print 3D parts that are compliant with the customer quality and regulatory requirements such as bio-compatibility and non-animal origin. SUT design and development must align and grow with the customer's product development based on phase appropriate requirements, manufacturing strategy, and risk-assessment.
According to Brian Neuman, a principal engineer at BPI Labs, the company has approximately 50 injectables in various phases from early R&D to commercial manufacturing and packaging. With so many products in development, single-use technology is particularly suited to their operation.
“There are companies that just manufacture a product nonstop and never have to make a change,” says Neuman. “But that is not the goal of our company. We are always trying to expand what we produce here, and that just inherently means we will have different requirements along the way.”
Given their unique and constantly changing requirements, BPI Labs decided to outsource the nonproprietary SUT assemblies and systems to an experienced company that could provide more flexibility. Neuman says it was imperative that the partner consult and provide expertise throughout the process.
“We were able to have meetings with them to bring up all the specific requirements we have for our facility and our process,” says Neuman. “When we did, the general response was ‘Yes, we can do that,’ as opposed to ‘That is not in our standard offering.’"
This article was written by Meghan Elizabeth, Manufacturing Operations Manager for IntelliTech, Inc., Saint Petersburg, FL. She directs the standard and custom single-use-technologies (SUT) manufacturing operations and oversees SUT product development strategy and tech transfer of products from development to production. For more information, visit here .