Freudenberg Medical, a global contract design and manufacturing provider to the medical device industry, is expanding its manufacturing operations in Alajuela, Costa Rica. The expansion project adds 8,600 square feet to the existing facility which includes construction of an additional ISO Class 7 cleanroom for catheter manufacturing and assembly, molding, extrusion, and packaging, as well as added office space.  New technology includes an advanced thermoplastic extrusion line which can produce tubing from 4 inches to 170 inches long with capacity of up to 1 million parts per month, plus additional injection molding machines.

“Costa Rica has grown as an important medical device cluster in recent years and Freudenberg Medical is part of that story,” said Dr. Max Kley, CEO of Freudenberg Medical.  “Freudenberg’s FDA-registered cleanroom operation is located in the Coyol Free Zone, a business park that is a central hub for life science companies and medical device OEM manufacturing sites.  In order to keep pace with rapid business growth, Freudenberg Medical has decided to increase its capabilities and capacity for catheter manufacturing, assemblies, injection molding, and medical tubing.

Learn more about Freudenberg Medical Costa Rica operations.

Rice University engineers from five laboratories are part of a $33 million national effort to develop a wireless, fully implantable device that can control the body’s circadian clock, halving the time it takes to recover from jet lag and similar disruptions to the body's sleep/wake cycles.

Led by Northwestern University and funded by the Defense Advanced Research Projects Agency (DARPA), the project will blend bioelectronics, synthetic biology and traditional electronics to create a "living pharmacy" that produces the same peptide molecules the body naturally makes to regulate sleep cycles. The device could be a powerful tool for military personnel, who frequently travel across multiple time zones, as well as first responders and other shift workers who oscillate between overnight and daytime shifts.

© Northwestern University | https://cscb.northwestern.edu/

Faculty in Rice's Brown School of Engineering will lead the development of key components of the proposed technology. Omid Veiseh, assistant professor of bioengineering, will oversee the creation of engineered cells that produce the therapeutic biomolecules, and Jacob Robinson, associate professor of electrical and computer engineering, will oversee the development of the wireless bioelectronic implant that houses the engineered cells and regulates drug production.

Called NTRAIN (Normalizing Timing of Rhythms Across Internal Networks of Circadian Clocks), the project is part of DARPA's Advanced Acclimation and Protection Tool for Environmental Readiness (ADAPTER) program to help address the challenges of travel, including jet lag, fatigue and gastrointestinal issues.

"Sleep control is something we can track while we develop this implant, but the real innovation here is being able to produce drugs inside the patient," Veiseh said.

The NTRAIN team will engineer cells to produce peptides to regulate sleep cycles. The engineered cells will respond to light, which will be delivered via bioelectronic controls that adjust timing and dose. Veiseh, who's leading the effort, said pharmaceutical companies often make drugs using industrial scale bioengineering.

"If we can bring all of that manufacturing right into the patient and produce high-quality compounds on an as-needed basis, the possibilities are infinite," Veiseh said. For a start, the technology could be used to manage diabetes and other chronic diseases where people regularly inject themselves with drugs.

The implant's power and communications will be delivered by a weak magnetic field generated by a wearable device. In a pioneering demonstration in 2020, Robinson and colleagues showed "magnetoelectric" technology could provide both power and communications for neural stimulators no larger than a grain of rice.

Robinson said the technology will provide plenty of power while enhancing device security.

"We'll design the device so it can only communicate in the near field, meaning only over a couple of centimeters," he said. "So you'd essentially have to be in contact with the device in order to hack it."

Veiseh and Robinson said an additional safety feature will allow a user to deactivate the device permanently by sending a signal for the engineered cells to immediately kill themselves.

The first phase of the highly interdisciplinary program will focus on developing the implant. The second phase, contingent on the first, will validate the device. If that milestone is met, then researchers will test the device in human trials as part of the third phase. The full funding corresponds to $33 million over 4 1/2 years.

Rice electrical engineer Kaiyuan Yang will design an application-specific integrated circuit to handle back-end functions and integrate with the bioelectronic controls. Rice bioengineer Isaac Hilton will optimize the cells' drug-making abilities, and Rice neuroengineer Caleb Kemere will test implants in rodents in the leadup to human trials.

Circadian clock research will be led by sleep experts at Northwestern's Center for Sleep and Circadian Biology. Engineers from Northwestern, Carnegie Mellon University and Blackrock Microsystems will also develop bioelectronic components.

"This control system allows us to deliver a peptide of interest on demand, directly into the bloodstream," said NTRAIN principal investigator Jonathan Rivnay, an assistant professor of biomedical engineering in Northwestern's McCormick School of Engineering. "No need to carry drugs, no need to inject therapeutics and — depending on how long we can make the device last — no need to refill the device. It's like an implantable pharmacy on a chip that never runs out."

Robinson and Kemere are each associate professors of electrical and computer engineering and of bioengineering. Yang is an assistant professor of electrical and computer engineering, and Hilton is an assistant professor of bioengineering and of biosciences. Veiseh, Robinson, Kemere and Yang are members of the Rice Neuroengineering Initiative, and Veiseh and Hilton are CPRIT Scholars of the Cancer Prevention and Research Institute of Texas.

Other members of the NTRAIN team are Fred Turek, Martha Hotz Vitaterna, Josiah Hester, Guillermo Ameer, Peng Jiang and Phyllis Zee, all of Northwestern; Doug Weber, Tzahi Cohen-Karni, Darcy Griffin, Carl Olson and Matt Smith, all of Carnegie Mellon; Karrie Fitzpatrick of the University of Minnesota; Florian Solzbacher of the University of Utah; and Rob Franklin of Blackrock Microsystems.

The United States Food and Drug Administration (FDA), Medical Device Innovation Consortium (MDIC), ISACA, and medical device industry stakeholders developed the Case for Quality Voluntary Improvement Program (VIP) to shift the mindset of medical device manufacturers beyond regulatory compliance and toward continuous improvement. After a pilot launch in January 2018, the Case for Quality Collaborative Community has now transitioned the VIP from a pilot into a fully operational program.

The VIP leverages ISACA’s Medical Device Discovery Appraisal Program (MDDAP) which provides a model and method by which device makers can measure their capability to produce high-quality devices with the goal to improve patient outcomes. The MDDAP framework is a version of the ISACA Capability Maturity Model Integration (CMMI) that has been tailored specifically for this medical device industry program.

The VIP includes a multi-pronged approach: a combination of annual MDDAP appraisals against a set of best practices, quarterly check points with performance reports, and a supportive regulatory environment. Together, this approach empowers medical device manufacturers to design, build, and deliver safe and innovative products to market faster.

In the VIP, an experienced appraisal team evaluates an organization’s capabilities through conversations with individual contributors, systems demonstrations, and site tours. The results are then synthesized for the organization to easily identify areas of strength to reinforce and prioritize opportunities for improvement.

The VIP is a continuous improvement method designed to help the Collaborative Community understand how to develop better quality and outcomes, both within an organization and across industry. Information is collected during an appraisal to evaluate how work is actually performed, highlight capabilities and activities that add value, and drive discussions that align and prioritize opportunities with business performance objectives.

In the supportive regulatory environment, participants were able to accelerate device improvement and speed to market. Results reported by pilot participants include:

• Capacity increased by 4x due to improvements and changes resulting from the appraisal
• 65% increase in daily production
• 27% decrease in time to close complaints
• Greater than $15 million in product sales
• Shifting from tactical to strategic thinking
• Identifying potential issues earlier, taking action before negative impact
• Increasing rigor and predictability in new product development
• Improving risk mitigation of nonconforming products, process control, and supply chain

The fully operational program has formalized the collaborative oversight used through the pilot into an official Governing Committee which includes members of MDIC, FDA, and industry, with ISACA and relevant collaborators serving as advisors. Iterative improvements and enhancements for the program are proposed through facilitated VIP working groups. This governance structure engages all stakeholders in seeking beneficial solutions through the sharing of information and ideas.

“We are excited that the VIP, which utilizes ISACA’s MDDAP, is now transitioning to a fully operational program. This allows better medical devices to be innovated faster and at lower costs,” says Nader Qaimari, ISACA chief product officer. “ISACA is proud to have a hand in driving sustainable improvements for medical device quality, in turn offering better patient safety outcomes.”

A research team from Los Alamos National Laboratory and Purdue University have developed bio-inks for biosensors that could help localize critical regions in tissues and organs during surgical operations.

"The ink used in the biosensors is biocompatible and provides a user-friendly design with excellent workable time frames of more than one day," said Kwan-Soo Lee, of Los Alamos' Chemical Diagnostics and Engineering group.

The new biosensors allow for simultaneous recording and imaging of tissues and organs during surgical procedures.

"Simultaneous recording and imaging could be useful during heart surgery in localizing critical regions and guiding surgical interventions such as a procedure for restoring normal heart rhythms," said Chi Hwan Lee, the Leslie A. Geddes Assistant Professor of Biomedical Engineering and Assistant Professor of Mechanical Engineering and, by courtesy, of Materials Engineering at Purdue University.

Los Alamos was responsible for formulating and synthesizing the bio-inks, with the goal of creating create an ultra-soft, thin and stretchable material for biosensors that is capable of seamlessly interfacing with the surface of organs. They did this using 3D-printing techniques.

"Silicone materials are liquid and flow like honey, which is why it is very challenging to 3D-print without sagging and flowing issues during printing," Kwan-Soo Lee said. "It is very exciting to have found a way to create printed inks that do not have any shape deformation during the curing process."

The bio-inks are softer than tissue, stretch without experiencing sensor degradation, and have reliable natural adhesion to the wet surface of organs without needing additional adhesives.

Craig Goergen, the Leslie A. Geddes Associate Professor of Biomedical Engineering at Purdue University, aided with the in vivo assessment of the patch via testing in both mice and pigs. The results showed the biosensor was able to reliably measure electrical signal while not impairing cardiac function.

The research was published today in Nature Communications. It was funded by Science Campaign 2.