Working with CDMOs allows manufacturers to focus their time and effort on research and development and commercialising their product portfolio. Yet, despite the critical role of innovative technologies in developing medical devices, medtech manufacturers have long shied away from contracting out their manufacturing operations.
Unlike consumer goods or food products, in industries where contract manufacturing is well established, medical devices have considerably longer development timelines. Other barriers include the complicated regulatory environment and highly specialised and often product-specific manufacturing needs of medical devices. Moreover, these restrictions can make it hard for medical device OEMs to change their CDMO partners between different development stages, leading to more apprehension in collaborating in the first place.
Nonetheless, in recent years, manufacturing advances have made CDMOs an attractive bargain for many medtech companies, such as those working on diagnostic imaging and cardiovascular devices. “For most medtech companies, the expertise lies in the products that they build, and not in processes [involved in manufacturing them],” says Sean Gilligan, now COO of Amplitude Vascular Systems, who spent almost three decades at Boston Scientific, including 15 years as vice-president program management, R&D.
By partnering with CDMOs, medical device companies can gain time and insights that they can channel towards what they do best: making innovative medical devices for different conditions.
The number of CDMOs serving the specialised needs of medical device developers is growing. “New doors are being opened every day via technological advances,” says Gilligan. One of the most impactful among them is continuous manufacturing.
Benefits of continuous manufacturing
Medical device companies typically manufacture their products in small batches to closely monitor quality and leave room for iterations. The downside is that raw materials cost more, and the manufacturing processes can be inefficient. Batch manufacturing involves a lot of stop-starts between and during the production of each batch. A lot of product testing happens at virtually every stop. In contrast, continuous manufacturing tests fewer products as a proportion of total units made. By eliminating the stop-starts, it increases production speed and lowers per-unit costs.
For growing companies, it provides access to technical labour and skills that they might not have. It also makes them innovatively flexible. Instead of committing resources to a particular product or variants, they can work on multiple product lines. Conventionally, manufacturers adopted continuous manufacturing for these reasons. But the world is shifting. “Now, it’s also about how you add the highest-level value for the amount of labour you put into a particular process,” says Gilligan.
“When you get to the higher volume and have a good line of sight for what you’re going to do for an extended period of time, continuous manufacturing really comes into its own.”
Sean Gilligan
For example, continuous manufacturing with CDMOs streamlines supply chain management. Unlike a single manufacturer buying small quantities of raw materials from one or a few suppliers, CDMOs can get price discounts. This not only lowers the price of manufacturing but also makes them, and, in turn, medical device companies, more immune to shocks in the raw material supply chain. The manufacturers also gain flexibility on the demand side and can adjust production in response to shifts in consumer needs.
Deploying continuous manufacturing, either in-house or in collaboration with CDMOs, can also ease the burden of stringent quality control requirements. “It streamlines quality management because changes in process parameters and trends can be detected early,” says Professor Anne Vanhoestenberghe, director of Manufacture of Active Implants and Surgical Instruments (MAISI), a national facility housed at St Thomas’ Hospital in London. In continuous manufacturing workflows, quality monitoring is often integral to manufacturing. “With continuous data assessments, you can spot trends early before they lead to something detectable in the final piece,” adds Vanhoestenberghe.
Together, these benefits make medical device companies more agile. Presently, advanced medical devices often have timelines of commonly three to seven years; for high-risk or highly novel devices, timelines can exceed a decade from the initial idea to commercialisation. By making production more efficient and coupling it with real-time quality control, continuous manufacturing accelerates time to market, bringing more medical devices to patients.
The benefits of continuous manufacturing are most evident in end-to-end production. “When you get to the higher volume and have a good line of sight for what you’re going to do for an extended period of time, continuous manufacturing really comes into its own,” says Gilligan. However, implementing it only partially or for devices produced at smaller volumes could help, too. Moving a few key subprocesses to a manufacturing mode could deliver substantial gains in operational efficiency.
Enabling manufacturing technologies
Whether end-to-end or for a few key processes, continuous manufacturing is heavily reliant on enabling technologies such as additive manufacturing and scalable microfluidics. While they lower the labour requirement, they are expensive to set up. “You can get the benefit over time, but you need to make that kind of investment,” says Gilligan. For it to make sense, Gilligan adds, “You want to make sure that your equipment and your processes are going to be well utilised.” If not, working with CDMOs is often a more favourable alternative to setting up in-house continuous manufacturing operations.
One of the key technologies is continuous digital light manufacturing (cDLM), which combines the flexibility of additive manufacturing with the speed of digital light processing. With CDMOs offering cDLM as a service, manufacturers can quickly iterate through prototypes and avail of scalable, fast and on-demand production of medical devices, or parts thereof. Beyond faster production cycles, it saves cost by eliminating material waste. Additive manufacturing is also unlocking new medical device designs. “3D printing achieves shapes that can have internal recesses or form factors that weren’t possible previously,” says Vanhoestenberghe.
Microfluidic technologies, a feature of many medical devices, are also shaping how medical devices are manufactured. Scalable microfluidics allows for continuous synthesis of nanoparticles, like plasmonic nanomaterials used in emerging diagnostics. Another prominent technology is the continuous production of nitinol tubes, a superelastic and shape-memory material.
Continuous draw methods provide an uninterrupted supply of these tubes, speeding up the production of a wide range of medical devices like stents and catheters. Automation and robotics are amplifying the speed of these technologies, yielding further efficiency gains for continuous manufacturing.
But not all medical devices can be made continually. The more steps involved in making a device, the harder it is to automate. “If you need to assemble a lot of parts, ultimately everything comes to a stop in the cleanroom where a manual operator has to handle the device,” says Vanhoestenberghe.
“Improvements in automated visual inspection for medical devices could potentially increase the range of products that can be manufactured using continuous manufacturing.”
Anne Vanhoestenberghe
With highly precise assembly machines, many medical devices can now be made with little or no human assembly. By reducing steps that need human intervention and ensuring that fewer parts are rejected by quality control, high-speed, highprecision assembly enhances the viability of continuous workflows. An important bottleneck, however, is testing the medical devices as they are manufactured.
“Improvements in automated visual inspection for medical devices could potentially increase the range of products that can be manufactured using continuous manufacturing,” says Vanhoestenberghe. In the other direction, continuous manufacturing of high-quality, precise parts speeds up assembly of medical devices.
Lessons from pharma manufacturing
While contract manufacturing has been mainstream in pharma for decades, continuous manufacturing processes are relatively recent in that industry as well. Pharma manufacturing is more amenable to continuous operation because manufacturing therapeutics typically doesn’t require discrete assembly or fabrication steps. “For radioisotopes, which have to be manufactured on demand or drugs that have to be patient-specific, batch production is the preferred mode,” says Vanhoestenberghe.
But even for therapeutic products that require some assembly or are made to order, the pharma industry has had some success with continuous manufacturing. These have been possible largely due to modular manufacturing platforms, flexible supply chains, and integrated development and manufacturing approaches. By adopting these trends, medical device companies too can achieve faster product iteration and development, and smoother regulatory approvals.
Lastly, medical devices with the greatest risk, such as surgical valves and defibrillators, require clinical trials before they are approved. Medical device companies can learn from how pharma clinical trials have made use of continuous manufacturing concepts like adaptive supply chains and flexible manufacturing methods. Additionally, unlike in pharma, iterative clinical trials are the norm in the medical device industry. Insights on how a device performs in clinical settings are brought back into the development of future iterations. Since continuous manufacturing allows medical device companies to develop product variants faster, it can speed up the iterative cycle and shorten clinical trial timelines.
Improved regulatory compliance
Regulatory compliance can feel like ever-shifting goal posts for medical device manufacturers. The regulations governing medical devices, particularly in Europe, keep changing with new trends in healthcare and sustainability, and other macro factors. Often, these shifts necessitate an adjustment in manufacturing processes, which can prove disruptively costly for smaller medtech companies.
Continuous manufacturing makes medical device companies more resilient to these shifts. By integrating real-time quality monitoring throughout manufacturing workflows, manufacturers can achieve continuous quality monitoring. Instead of testing a few samples per batch, this approach validates the safety and quality of devices as they are produced. This reduces operational risks, improves regulatory compliance, and delivers more value to the patients.
As more medical device manufacturers turn to continuous manufacturing workflows, the industry could benefit from improvements in sustainability, material efficiency and device safety. But, for the most impact, continuous manufacturing should be accessible to medical device manufacturers of all sizes. “What we need is a bridge between batchbased manufacturing and CDMOs that implement continuous manufacturing once the numbers justify [it],” says Vanhoestenberghe, “and different types of CDMOs suited for different scales.”
