Originally Published MDDI April 2001

R&D Horizons

Approaching concurrent engineering as a mind-set enables design and manufacturing teams to bring products to market sooner.

Ellen Pauli

Many who attempt to implement concurrent engineering across an organization and partner network meet with resistance and frustration, because they are too busy trying to adopt the principles—not the thinking behind them. At its core, concurrent engineering is the application of proactive thinking; the typical principles of forming a cross-functional team, estimating a project's scope at its outset, using the latest technology, and performing design reviews at every stage simply support this premise. Therefore, if all participants understand that they can help bring a product to market faster and less expensively by applying concurrent engineering at each project phase, the challenge is well on the way to being met. For Proxima Therapeutics Inc. (Alpharetta, GA), a designer and developer of cancer treatment products, and its silicone device manufacturing partner, Vesta Inc. (Franklin, WI), for example, embracing concurrent engineering with this mind-set has helped them reap its time- and cost-saving advantages.

When concurrent engineering is practiced in a partnership, "it is essential for the partner to be involved early and to understand the big picture," says Rance Winkler, vice president of research and development at Proxima. This helps to foster proactive thinking because the partner can be looking down the road at ways to reduce the cycle time. If a company limits its partner's involvement to only one aspect, the full benefit of the partner's expertise is not realized and the OEM is not likely to gain any efficiencies the partner can lend. "In our experience with Vesta, getting them involved in all aspects meant they were committed to our ultimate goal and to working proactively to meet it," Winkler says.

A CASE IN POINT

Proxima and Vesta recently put their concurrent engineering philosophy to work on a new technology, conceived and developed by Proxima, for a radiation therapy product for treating breast cancer. The patented device, called the MammoSite Radiation Therapy System (RTS), is a balloon catheter designed for temporary implantation to deliver radiation to a resected tumor cavity. The catheter and balloon subassembly, manufactured by Vesta, consists of a silicone applicator shaft (catheter), a balloon, a silicone tip assembly, and a polycarbonate stiffener with end cap (see Figure 1). A central lumen in the catheter serves as the pathway for placement of a radioactive seed, while a smaller lumen is used for inflation of the balloon. The product is currently in clinical trials. (An investigational device, the MammoSite RTS is limited by federal law to investigational use.)

Figure 1. The catheter's central lumen is used in placing a radioactive seed; a smaller lumen is used for balloon inflation.

ASSEMBLING A TEAM

The first concurrent engineering step in this project was to form a cross-functional team with representatives from research and development, engineering, manufacturing, regulatory affairs, quality, marketing and sales, purchasing, scientific affairs (to deal with radiation issues), and clinical affairs. Having a team "allowed everyone to be involved in the project at all times," Winkler states. "At any time, when any issue came up, we could all pull together and make decisions quickly—addressing challenges in minutes instead of the days or weeks it might take otherwise."

SEEING THE WHOLE PICTURE

It was important for the cross-functional team to be in place in order to execute the next concurrent engineering step, which was to calculate the project's scope. Together, the team determined timelines, cost estimates, and all of the product life-cycle activities that would be involved at each phase. An important step was constructing a Gantt chart, which permitted everyone to see what would be happening at every moment and helped determine which tasks could be performed simultaneously by team members.

Team members consulted the chart daily, with a special focus on critical development path items. "At weekly team meetings, as well as spontaneous meetings, we asked, 'Is there any reason we won't be able to meet the timeline?'" Winkler explains. "If there was, we resolved it."

At this stage, Proxima began working with Vesta—whose services include silicone extrusion, molding, bonding, and assembly—on identifying ways to shorten the development path. For example, it was determined that, during the initial concept phase, Vesta could begin evaluating materials and preparing for tooling.

ON TO DESIGN

With team assembly and project scope estimations behind them, the team was ready to move on to design. (The device design would be based on a similar balloon-catheter concept that had been developed for brain cancer radiation treatment.) The balloon catheter is inserted into a tumor cavity, following breast tumor removal, to deliver radiation homogeneously to the target tissue. Compared with conventional interstitial brachytherapy—which delivers radiation to a tumor site through a complex, multicatheter system—the device places a single radioactive source in the center of a silicone balloon. This causes the radiation to propagate outward in a homogeneous manner to a uniform and controlled depth around the balloon to the target tissue.

To determine optimal balloon sizes and shapes for accommodating the various sizes of tumor cavities, Proxima interviewed surgeons, held focus groups, observed lumpectomies, and studied MRI images and CT scans of tumors and cavities. "Based on surgeons' findings, we decided to develop the product in both spherical and ellipsoidal shapes," states Winkler. "The balloon size and shape being used in our clinical trial has a 4-cm spherical diameter, while the ellipsoidal balloons, currently being developed, will be available in multiple sizes."

Achieving the exact balloon shapes and sizes was critical for ensuring proper conformance to the resected tumor cavities. Symmetry was important as well, says Winkler, for maintaining a homogeneous distribution of the radiation dose. "We needed the catheter shaft to be positioned at the balloon's exact center, so that in practice, when the radioactive seed is introduced, it irradiates evenly."

To meet these criteria, "it was very valuable to have an experienced partner working with us from the start," Winkler explains, "one with knowledge and understanding of silicone material properties along with experience in balloon production. This helped us establish a practical set of design parameters."

Concurrently, Vesta began testing an array of silicone elastomers to assist with material specification, including the bonding material for attaching the balloon to the catheter. The device components are made from molded and extruded silicone elastomers to ensure the highest possible biocompatibility. Silicone, being a radiolucent material, does not inhibit the delivery of radiation to the tumor site.

THE CAD ADVANTAGE

The use of CAD simulations with 3-D modeling was another concurrent engineering component that accelerated the development cycle and saved costs. The development of design reviews was facilitated by this strategy because the process allowed the companies involved to evaluate the design in 3-D and make modifications in a timely manner. Redesigns downstream were minimized as well. In addition, CAD modeling minimized tooling changes, enabling the analysis and evaluation of design changes before metal was cut.

ENSURING MANUFACTURABILITY

As a result of its early involvement, Vesta was able to recommend a change in the balloon's wall thickness. "The initial design called for thinner walls," explains Bill Woinowski, research and development manager at Vesta, "but with that specification, we would have been unable to ensure consistent wall thicknesses. Making the walls slightly thicker allowed us to obtain the consistency needed for proper balloon inflation and radiation distribution. It was an example of refining design specifications to optimize the product's manufacturability, while ensuring best quality."

RAPID PROTOTYPING

A proprietary rapid prototyping process was employed to accelerate prototype modeling and assembly. The process is based on the molding of liquid silicone rubber in low volumes with rapid setup, using liquid injection molding presses and pumps designed in-house. The prototypes are molded using the same material specified for full production units. This allows engineers to evaluate devices in their final form, which yields more accurate test results and may help to shorten the approval process. All research and development projects using the process offer full traceability.

TESTING AND SECONDARY OPERATIONS

In-process testing was conducted for burst strength, leakage, and symmetry. These tests included 100% testing on all of the balloons to ensure that specifications were met.

Additional secondary operations included use of a low-profile tipping and marking technology to produce radiopaque markings that extend continuously around the diameter of the catheter. This permits the catheter's position to be viewed from any angle with conventional imaging.

CONCLUSION

Through the use of concurrent engineering, the device manufacturer and its principal supplier met their deadline by completing the product design approximately nine months earlier than would have been possible without such cooperation. In terms of cost, the project was within 5% of the original estimate. As Winkler states, "This was truly an example of engineering and manufacturing working together, with an eye on the next phase at all times, to solve a design challenge."

The MammoSite Radiation Therapy System (RTS)*, conceived and developed by Proxima (Alpharetta, GA) with the manufacturing assistance of Vesta Inc. (Franklin, WI), is a novel approach to radiation therapy for breast cancer treatment. Unlike conventional radiation therapies, it delivers radiation to tumor cavities from the inside out. According to the companies, this focuses the radiation dose on the area of the breast that is at the highest risk for a recurring tumor, while significantly reducing both the duration and complexity of the therapy.

The MammoSite incorporates a balloon catheter intended for temporary implantation into a resected tumor cavity to deliver radiation directly to the tumor site. The device permits radiation therapy to be administered over a period of 5 days—an 85% reduction compared with the 7 weeks required by conventional external-beam radiation therapy. Furthermore, the device's balloon catheter design is intended to offer simplified treatment planning for the delivery of radiation to the target tissue. Traditional interstitial brachytherapy requires numerous catheters for radiation delivery.

The catheter may be inserted into the tumor cavity during a lumpectomy, or during an outpatient procedure at a later date. After the balloon portion of the catheter is placed within the cavity—with the catheter's applicator shaft extending outside the breast—the balloon is inflated (filled) with a sterile saline solution. The catheter exit site is dressed, and the patient is sent home. Once the patient has recovered from surgery, radiation therapy is administered on an outpatient basis in brief daily sessions. During these sessions, computer-controlled equipment delivers the radiation using a tiny radioactive seed attached to a wire. The wire travels through the catheter and into the balloon, where the radiation propagates outward to all points surrounding the tumor cavity (Figure 1). The balloon catheter is removed after the last therapy session.

Figure 1. Placed within the breast via balloon catheter, the radioactive seed delivers homogeneous radiation to the target tissues.

"The device makes local radiation delivery quick, simple, and reproducible," says Robert R. Kuske, MD, radiation oncologist at Ochsner Clinic (New Orleans), one of the clinical trial sites where patients have completed treatment. Kuske, the principal investigator of the clinical trial, hopes that shortening the therapy duration will give more women access to a breast-conserving treatment—a lumpectomy followed by radiation therapy—rather than the traditional mastectomy.

COMPARISON WITH CONVENTIONAL INTERSTITIAL BRACHYTHERAPY

"The concept behind brachytherapy is to place radioactive sources as close as possible to the area being treated (i.e., a tumor site), which can require as many as 20 to 25 catheters in conventional interstitial brachytherapy," says Proxima's research and development vice president Rance Winkler (Figure 2). "By contrast, with the MammoSite, only one catheter is used to place a single radioactive source in the center of its balloon. When the radiation source is located within the balloon, the radiation behaves in much the same way that light behaves when it radiates outwardly from its source within a light bulb. In a spherical balloon, this would mean the radiation is delivered in a 360° (spherical) radius, reaching areas that conventional interstitial brachytherapy misses." Moreover, the time-consuming and tedious effort needed for dose mapping that conventional interstitial brachytherapy requires at the front end is apparently eliminated. Treatment is also administered without painstaking implantation of multiple catheters, and without leaving scars from multiple catheter incisions. "Only one entry point is required, and this implantation is often done at the time of tumor removal," Winkler notes.

Figure 2. Performing conventional interstitial brachytherapy can require the application of 20–25 catheters to position radioactive sources near the tissue to be treated.

A NEW OPTION

Currently, only 40% of eligible breast cancer patients choose a lumpectomy over a mastectomy. It is the hope of the device developers that the MammoSite RTS will increase that figure, giving patients a new and less-traumatic option.

*Caution: Investigational device. Limited by federal law to investigational use.

Ellen Pauli is the senior technical writer for Tritech, a Chicago area-based firm providing business-to-business consulting to the medical device manufacturing industry and other manufacturing industries nationwide.

Copyright ©2001 Medical Device & Diagnostic Industry