Like our determined hippopotamus in “The Hippo-Not-Amus”, biotherapeutics are steadily finding mash-ups with medical devices to find creative medical solutions. Novel combination products are being developed and gaining approval in the USA and Europe. In fact, over 30% of biotherapeutics in development are combination products. Novel biodegradable materials, bioelectronic sensors, improved biocompatibility, miniaturization to the nanometer and micrometer scale and other innovations have driven a wave of products. But are these products devices or drugs, or something in between? Is the development path faster as a device or pharmaceutical? Or does the industry and regulators need to consider a new way to develop, review and approve biotherapeutic devices?

    The FDA has an Office of Combination Products (OCP), but it does not regulate combination products, rather it is responsible for designating an FDA Center (Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, or Center for Devices and Radiological Health) to provide premarket review and postmarket regulation. A product’s primary mode of action is used as the basis for that decision. The agency determines a product’s PMA, but manufacturers have the option of submitting a Request for Designation, providing information to support their products’ designation as a drug (CDER), biologic (CBER), or device (CDRH). Once a company knows the jurisdiction of its product, it can establish a cGMP program for manufacturing. https://bioprocessintl.com/manufacturing/formulation/combination-products-for-biotherapeutics-309329/

    BioTether Sciences is developing novel biopharmaceuticals and medical devices that incorporate proteins to exploit ligand-receptor or antigen-antibody binding. We also provide consultation and testing services to help others develop novel therapies for unmet medical needs. Here are a few examples of drug-device mash ups that are exciting and informative to us.

    A great, recent advance is the artificial pancreas. In an NIDDK sponsored study the artificial pancreas, also known as closed-loop control, is an “all-in-one” diabetes management system that tracks blood glucose levels using a continuous glucose monitor (CGM) and automatically delivers the hormone insulin when needed using an insulin pump. In a recent clinical trial, results showed that the artificial pancreas system was more effective at controlling blood glucose levels associated with type 1 diabetes.https://www.nih.gov/news-events/news-releases/artificial-pancreas-system-better-controls-blood-glucose-levels-current-technology

    What about the artificial lymph node? In a proof-of-concept study in mice, scientists used a specialized hyrdrogel that acts like a lymph node to successfully activate immune cells to fight cancer. This strategy could be used recruit immune effector cells to target tumors or to dampen the immune response to self antigens, or become more effective at warding off infection. https://www.sciencedaily.com/releases/2019/04/190418141559.htm

Hydrogels or other natural or artificial polymers can be used to deliver drugs, cells, or just provide favorable conditions for wound healing or prevention of infection.  These products show great promise. In some regulatory jurisdictions they are treated as medical devices, in others, they may be considered a drug.Ventrix, a University of California San Diego spin-off, successfully conducted a first-in-human trial of an injectable hydrogel, designed to repair damage and restore cardiac function in heart failure patients who previously suffered a heart attack.https://physicsworld.com/a/hydrogel-to-repair-heart-proves-safe-to-inject-in-humans/

    Nanomedicine combines the promise of nanotechnology with pharmaceutical intervention to open up entirely new avenues for treatments. A recent surge in the development and application of nanoparticles for biomedical uses includes engineering magnetic particles for magnetic resonance imaging, magnetic hyperthermia and targeted drug delivery.swarms of nanoparticles that deliver vital drugs to the brain, offering new hope to patients in the early stages of a stroke or with glioblastoma. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773933/

Implantable devices have come a long way from the days of faulty stainless steal hip replacements. Improved materials, better more thorough biocompatibility studies, and miniaturization have improved products greatly. Implantable sensors and electrodes that take advantage of new materials, device designs and fabrication strategies enable new and improved biomedical applications. Electronics are used to treat health conditions and injuries, but often they have to be surgically implanted, so when they malfunction or their batteries die, patients have to go back under the knife. Many materials are safe for use in the body, but some leach chemicals when they break down releasing toxic compounds. New materials are being used to design medical devices, for instance, a biodegradable disc-shaped wireless device about the size of a nickel, stimulates peripheral nerves with weak electric shocks. When the nerve is healed, the body naturally breaks down the device and safely removes the waste.https://www.mccormick.northwestern.edu/news/articles/2018/10/researchers-demonstrate-first-example-of-a-bioresorbable-electronic-medicine.html

    The biopharmaceutical-device mash-up is sure to achieve great things. Just like the hippo-not-amus, we need to focus on making the most out of what we have. The incredible properties of biopharmaceuticals (safe, potent, specific) with the precision of medical devices (targeted, timely delivery and  control) is sure to impress.