Bringing life-saving medical devices to market takes innovation, courage, and technical expertise.
Biotech startup Lumicell knows commercialization also takes an immense amount of work carried out in a rigorously controlled quality system that meets strict FDA regulatory requirements. Based in Massachusetts, Lumicell has been working for over ten years to solve a potentially life-threatening problem for breast cancer patients: residual cancer left behind during lumpectomy procedures.
Med-tech startups focus their early efforts and investment on designing technologies and conducting the research necessary to demonstrate that their novel products can be safe and clinically effective for humans.
Winning FDA approval and the right to sell the new product, however, requires much more. Approval takes appropriate manufacturing and packaging facilities, robust quality systems and demonstration of rigorous manufacturing and testing processes in accordance with international and domestic standards.
“Not only are these manufacturing skills and resources often unavailable to med-tech startups, they are difficult to justify investing in prior to the product being approved for sale,” says Sean Madden, senior vice president of R&D at Lumicell.
Lumicell’s innovative combination medical device and imaging agent system remain in development and have not yet been approved by the U.S. Food and Drug Administration. Thankfully, some ideas are too powerful to be deterred by the challenge.
A landscape-altering breakthrough in cancer surgery
Women in the U.S. have a 1 in 8 lifetime risk of being diagnosed with breast cancer. Every two minutes, one new case is diagnosed. Breast cancer is the most common cancer in women around the world, with an estimated US incidence of 342,000 new cases in 2022 [1].
A lumpectomy, also known as breast conserving surgery (BCS), is the standard of care in treating non-invasive and early-stage breast cancer. During a lumpectomy procedure, the tumor and some surrounding tissue are removed. Pathologists process the excised tissue after the surgery and examine the tissue’s outer edge to infer whether cancer may remain in a patient’s body.
A “negative margin” (no cancer cells at the outer edge) infers all the cancer has been removed. A “positive margin” (cancerous cells at the edge) infers that cancer cells may have been left behind and the patient should undergo a second surgery.
Studies have shown that between 20-40% of procedures result in positive margins, indicating residual cancer that requires a second surgery to remove [2, 3, 4].
Cancer treatment evolves constantly but slowly, and rates of lumpectomies with positive margins have been trending downward over the last 5-10 years [5]. But that reduction has been gradual, and it seems that a reliable process for achieving negative margins requires a game-changing innovation.
Also, studies have shown that ~14% of patients with negative margins still have residual cancer left behind that is currently not addressed by any available surgical procedure [6]. In this more challenging scenario the unmet need can have serious consequences down the road.
But these are not numbers we need to live with.
To address these clinical needs, Lumicell is developing a novel imaging system consisting of a proprietary optical imaging agent, a hand-held imaging device, and patient-calibrated tumor detection software Together, they comprise the Lumicell Direct Visualization System (DVS), designed to illuminate cancer cells in real time and enable surgeons to see and remove residual cancer during the initial lumpectomy surgery. The proprietary optical imaging agent is also being tested in multiple solid tumor cancer types. The Lumicell DVS combines cutting edge drug design, advanced optics, and sophisticated algorithms to help solve one of surgical oncology’s most pressing issues.
A feasibility study in 230 breast cancer patients showed the potential of the Lumicell DVS to not only reduce positive margins during the initial procedure, but also guide the removal of residual cancer in negative margin patients, for whom there would otherwise be no surgical treatment [7]. Revolutionary breakthroughs in development like the Lumicell DVS require expensive and time-consuming clinical trials to prove safety and effectiveness, so they are rare and slow in arriving to market.
The manufacturing hurdle
Medical device development occurs in a number of stages. What someone might call “early-stage” could extend from R&D all the way to feasibility trials. From there, the device still needs to be tested in large human clinical trials and pass design validation and process qualification to produce a reviewable submission for FDA approval.
The full skillset a team needs to develop a medical device is rarely found under one roof. Lumicell has crucial core-competencies in-house:
- Top development talent to turn ideas and concepts into manufacturable products
- An in-house Clinical Operations team for designing and carrying out clinical trials and analyzing the results
- A management team with a solid understanding of the short- and long-term milestones they need to achieve and what practical steps need to be taken to get there
But they recognize when it is time to look outside of their organization when more specialized expertise is needed. Like many medical device startups, the Lumicell team excels at innovation. But they sought a strong partner for manufacturing a significant volume of the device and validating a scalable process.
Manufacturing proof-of-concept with a streamlined process
Matthew Salame, senior product development engineer, leads product development of the single use sterile cover that drapes over the reusable handheld probe. The sterile cover is designed to establish the focal plane of the imaging probe when scanning the surgical cavity and minimize cavity exposure to the device.
“We need this subsystem in place,” Matt says. “And we sought for someone to both commercially manufacture and package our subsystem as well as help us with the product development stages — creating engineering builds, prototypes, samples — so that we can do design verification and validation testing as part of our submission package to the FDA.”
Shortly after he arrived at Lumicell, Matt visited J-Pac Medical’s contract manufacturing facility to talk through engineering builds and a product realization plan. While there, he saw commercialized devices in production at scale. He remembers feeling that the Lumicell system could reach that point and make a difference.
But it would require a strong partnership.
“There are a lot of nuances associated with the engineering builds and the sterilization, manufacturing, and packaging of this product. We’re able to lean on J-Pac for their experience,” Matt says.
Lumicell works with multiple vendors across the production of its full system. Relationship management is key but pulls on its experts’ time. Not having the right partner could put stress on the entire operation. J-Pac connected Lumicell with a sterilization team in its network that could assist while working towards taking sterilization of the subsystem in-house to simplify Lumicell’s process.
Matt says, “They have many of the capabilities that we need that, in summation, help to create a more streamlined workflow for us,” including manufacturing, sterilization, packaging, and supply chain management.
There are many device manufacturers and many packaging suppliers, but fewer partners who can do both. And even fewer that can handle sterilization, manage the project’s supply chain, and assist with product development on top of it all.
“We’re meeting our milestones and we believe we are on track to succeed,” Sean says. “And I don’t think we could have gotten to this point without J-Pac.”
“It absolutely limits the amount of work we need to do to create traceability between additional suppliers or qualifying different suppliers or ensuring that they are in tight communication when the product goes from one facility to the other. The parts come in at J-Pac and finished product leaves J-Pac in a simplified process flow,” Matt says.
Lumicell’s team has been built to ensure the development of the best product possible, and its internal structure has proven robust enough to manage late-stage development of a complex device. The company is now laser focused on FDA submission for marketing approval and building out its commercial infrastructure.
“Success will be measured by FDA approval and widespread adoption in order to improve the current standard of care. We’re meeting our milestones and we believe we are on track to succeed,” Sean says. “And I don’t think we could have gotten to this point without J-Pac.”
Get your device over the manufacturing hurdle and into the market
Lumicell can see the opportunity ahead for patients, once its DVS is approved. Getting to market is complicated, and the hurdles along the way can’t distract you from your goal: to develop a safe and effective device that helps people.
Sometimes the best way to do that is to align with a strong, strategic partner. Contact J-Pac to assist your company with product development, preparation for FDA approval, and production at scale.
References
- American Cancer Society. Cancer Facts and Figures 2022. Atlanta, Ga: American Cancer Society; 2022.
- Hotsinpiller, WJ, Everett, AS, Richman, JS, Parker, C, Boggs, DH. Rates of margin positive resection with breast conservation for invasive breast cancer using the NCDB. Breast. 2021;60:86-89.
- Brouwer de Koning SG, Vrancken Peeters M-JTFD, Jóźwiak K, Bhairosing PA, Ruers TJM. Tumor Resection Margin Definitions in Breast-Conserving Surgery: Systematic Review and Meta-analysis of the Current Literature. Clin Breast Cancer. 2018;18(4):e595-e600.
- Smith BL, Lanahan CR, Specht MC, et al. Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery. Ann Surg Oncol. 2020;27(6):1854-1861.
- Piper, M.L., Wong, J., Fahrner-Scott, K. et al. Success rates of re-excision after positive margins for invasive lobular carcinoma of the breast. NPJ Breast Cancer. 2019;5:29.
- Dupont E, Tsangaris T, Garcia-Cantu C, et al. Resection of Cavity Shave Margins in Stage 0-III Breast Cancer Patients Undergoing Breast Conserving Surgery: A Prospective Multicenter Randomized Controlled Trial. Ann Surg. 2021 May 1;273(5):876-881.
- Hwang ES, Beitsch P, Blumencranz P, et al. Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence–Guided System: A Nonrandomized Controlled Trial. JAMA Surg. Published online May 11, 2022. doi:10.1001/jamasurg.2022.1075