Aligning value proposition: From Preclinical to Market for Medical Devices

Tim Pelura, CEO, Surpass Preclinical CRO talked on how medical device companies can align their strategy, from preclinical to market, with a focus on the value proposition, at www.bio2devicegroup.org event.

We are operating under a new reality now where power has shifted to the payers and the providers, said Pelura.  Medical device companies are evaluated based on safety and procedural efficacy as well as cost and value.  Increasingly heightened regulatory scrutiny and tightening FDA regulations have led to increase in audits (which were up 40% in the last year) and warning letters are (which were up 24% over the last 2 years).  Due to regulatory and reimbursement challenges, medical device companies are focusing their R&D efforts on improving already approved devices, rather than developing innovative new products.  Meanwhile startups are finding the landscape challenging due to funding challenges and increasing costs of bringing new products to market.

Healthcare Infostep (Photo credit: Wikipedia)

Inkeeping with the reality of pressures on payers that are transmitted down, new healthcare delivery models are emerging, and therefore, patient pathways are being modified to obtain to obtain better outcomes, with less cost.  Medical device companies will need to work with new business models, that solve significant problems and reduce overall costs.  Companies seeking growth will need to expand their offerings to target underserved populations and lower socioeconomic classes.

In essence, it is about the value proposition offered by the new product or service, “what benefit you provide for who and how you do it uniquely well”, said Pelura.  He advised, these “must-haves” in a business pitch, “describe your target buyer, the problem you are seeking to solve, and why you do it better than the alternative”.

Pelura walked the audience through the process of arriving at the value proposition.  First, companies must define the problem they are seeking to solve and identify correctly the need to solve the problem.  Next, they should try to go after obvious problems, rather than aspirational or “good to solve” problems.  And finally, they should try to address acute or critical problems.

In defining a solution, they should try to generate many ideas and then measure the viability of customer adoption of each idea using gain/pain ratio; what the customer stands to gain versus the cost of adoption of the new solution.  The best solutions are those that offer game-changing benefits, with minimal modifications to the existing process or environments, said Pelura.  Go for “Disruptive Innovations, that are Non-Disruptive to Adopt”, advised Pelura.   Medical device companies must visualize the entire process or patient pathway to ensure that the new solution would cause minimal disruptions, in the whole process.

While new technologies often emerge with a focus on engineering and progress to bench testing and then plan preclinical, and clinical strategies and only then consider navigating regulatory, market, and reimbursement challenges; in actuality, they should invert the process.  They should begin with considering reimbursement challenges, analyze the competitive landscape, study the market opportunity, give thoughtful consideration to the regulatory challenges, then consider clinical and preclinical strategy, before embarking on prototype and bench testing.  Because if the value proposition is wrong then a company can end up with a product that no one wants or needs, resulting in considerable waste of precious innovation dollars and time, said Pelura.

Speaking of Surpass, Pelura shared that preclinical Contract Research Organization, Surpass is doing things differently.  While having deep expertise as a preclinical CRO in helping medical device companies with their preclinical in vivo and human cadaveric studies, Surpass also seeks to impact the system, by probing and assisting their clients with questions that go to the value proposition.  Surpass assists the clients in designing the most translatable preclinical study by understanding issues of clinical end points, product’s desired features and characteristics, all the while keeping in mind who would be operating the device, studies and activities that might need to be completed to demonstrate the products, performance, safety, and efficacy, as well as data that would be required to drive reimbursement and more.  This novel process ensures that any preclinical testing performed is aligned to the new product’s value proposition, hence helping save valuable healthcare innovation dollars.  

The session was followed by Q&A.

 

Do’s and Don’ts of Pre-clinical Medical Device Development – talk by Jim Swick

Jim Swick, Chief Scientific Officer at LifeSciencePLUS http://www.lifescienceplus.com, gave a talk on Pre-clinical Medical Device Development at http://www.bio2devicegroup.org. He advised that it is important to ask some questions before taking the first step. These include, what is procedure or application for the device, who are the potential end users, and what might be anatomical challenges. Also market aspects should be considered like will the device reduce cost, significantly improve medical care, and would it satisfy or further complicate the existing mode of therapy. Study should begin with in-vitro testing to examine mechanical and ergonomic aspects of the device including if the device does what it is supposed to do, inside the blood or tissue. In-vivo testing should focus very strongly on satisfying safety requirements and examining anatomical compatibility.

For selecting the appropriate animal model, it is important to do review to identify precedents. Pitfalls of animal testing should be carefully considered. Translating data from animal to human is challenging. Despite many anatomical similarities, there are also many anatomical differences. There is no animal model that very closely mimics human anatomy and physiology completely. But certain animal models are good for certain regions of the anatomy. For instance, sheep is often a better animal model for spine devices. For challenging devices, it is absolutely important to also work on human cadavers. It is also important to remember that while some device work well in animals, these animals are often young and healthy, whereas, humans who might get these devices may be very sick or old. There are examples where some devices worked very well in young, healthy animals but failed in humans in first clinical trials. FDA’s primary concern in pre-clinical studies is with safety of the devices and that these devices would not kill an animal. Efficacy becomes a greater focus during human clinical trials. Swick discussed the importance of selecting a good SAB (scientific advisory board). Some advisory boards exclusively are formed with clinicians and that would be a problem. He suggested that SAB have a good mix of clinicians as well as scientists.

Dr. John Bashkin, VP of Bus Dev (www.zymera.com) presented on Next Gen Bioluminescent Probes: Ultrasensitive Biomarker Detection In Vivo and In Vitro Assays (www.bio2devicegroup.org)

Dr. Bashkin gave a background of bioluminescence and limitations of existing imaging modalities and then discussed the next generation probes being developed at Zymera. Bioluminescence imaging (BLI) technology improved tools for biological detection and imaging through nanotechnology allowing for noninvasive study of ongoing biological processes. Bioluminescence imaging utilizes native light emission from one of several organisms which bioluminesce. The three main sources are the North American firefly, the sea pansy (and related marine organisms), and certain bacteria. The DNA encoding the luminescent protein is incorporated into the laboratory animal either via a viral vector or by creating a transgenic animal. Many of the existing imaging modalities like MRI, Ultra Sound, and CT Scan used for imaging, show high resolution but low sensitivity. Bioluminescence gives good sensitivity which can be expanded but there are several limitations in the existing bioluminescence imaging technology. Cell transfection is not possible with certain cell types, short luciferase enzymes have half life in serum, emission wavelengths limit in-vivo sensitivity, there is limited color multiplexing, low in-vivo ATP concentrations, and limited spatial resolution.

Zymera technology overcomes most of these limitations, with injectible probes, mutated luciferase, energy transfer, quantum dots, and renilla luciferase, said Bashkin, and further expanded on each of these.  Attributes of the improved luciferase are that they are smaller and lighter with long serum half life.  Luc8 (renilla luciferase) is a form of luciferase that exhibits improved light output and serum stability over traditional versions of the enzyme.  Dr. Gambhir at Stanford has come up with 8 mutations that increase serum sensitivity 200 times and there is 4 fold increase in light output, as shown by Luc 8 data.  Zymera’s Bioluminescent Resonance Energy Transfer (BRET) probes, developed by Dr. Rao at Stanford, combine this recombinant form of renilla luciferase (Luc8) with quantum dots, enabling non radiative energy transfer from Donor to Acceptor.  The BRET Qdot probes can be targeted; conjugated with biomolecular recognition molecules (antibodies and peptides), or activity-based.  Quantum Dots from Life Technologies are made of semiconductor material with a polymer coating.  The BRET-Qdot probes allow tumor xenograft to be made from just 100 cells rather than 20,000 and enable the visualization of early stage metastasis in-vivo.  Zymera probes are active in serum and blood, can be multiplexed for in vivo imaging, and are designed as proximity and activity based biosensors. They do not require external illumination source, thus eliminating tissue autofluorescence and facilitate deep tissue imaging.  Currently in technology pipeline, there is non toxic version of Qdot, for use in humans, for diagnostic purposes.  Zymera is establishing collaborations with pharmaceutical and biotechnology companies for BRET-Qdot probe development and applications, and has active collaborations with OncoHealth, Genentech, and Amgen, said Bashkin.