Advancing Pharma and Medical Device Development with Novel Biomaterials

The poly(glycerol sebacate urethane) (PGSU) polymer platform Hydralese™ is a biodegradable drug delivery marvel that outperforms all commercially available equivalents. Secant Group is focused on implementing this new technology across indications, from ocular micro-implants that treat ophthalmologic disorders to orally administered gastroretentive rings that deliver antivirals to subcutaneous implants and injectables that treat neurological disorders, prevent HIV, and deliver contraception but its potential does not stop there. Stephanie Reed, Ph.D., Director of Translational Product Development, spoke with Pharma’s Almanac regarding Secant’s legacy as an aerospace textile provider to its expansion into pharma and medical device, as well as the future applications of this impressive biomaterial.

DAVID ALVARO (DA): Can you give me a primer on the history of Secant, including the original vision, focus, and technology upon which the company was founded, and how it has expanded from there?

STEPHANIE REED (SR): Secant is an 80-year-old company that has been evolving for many decades. We originally began working in the aerospace industry in the production of textiles for astronaut spacesuits and satellite antenna meshes — and we continue to support the aerospace business today. In the 1980s and throughout the 1990s, Secant expanded into the medical device world. We have very deep roots and a lot of maturity and penetration with our current medical device customers, and we continue to supply high-quality, lifesaving implantable textile components to these original equipment manufacturers (OEMs).

Within the last few years, Secant moved toward diversifying beyond textiles into fields that would complement our textile capabilities and healthcare focus, which prompted our parent organization, Solesis, to acquire Charter Medical. Charter Medical focuses on single-use technologies for the production of cell and gene therapies as well as for bioprocessing and blood management. That intersects well with what we do in textiles and biomaterials — there’s a lot of room for innovation to bring all of these facets together, like different points on a triangle.

When the novel biomaterial that we’re developing — poly(glycerol sebacate) (PGS) — is layered on top of that, it highlights the cross-functional nature of all these applications and the potential that arises from combining our proficiencies in device architectures, cell interactions, and polymer properties. Secant Group is unique because we play in all these major fields, and we’re not afraid to cross boundaries to tie concepts together to bring better solutions to market.

DA: Can you explain the fundamental science and what’s unique about PGS?

SR: PGS itself has been around for a long time, but it originally gained popularity in the early 2000s at MIT for tissue engineering in medicine. Even now, when you look in the academic literature, most of the PGS work is in the tissue engineering space. Secant, being a medical device company with a textile legacy, identified PGS about 10 years ago when scouting polymers to bring in-house because of its bioregenerative potential and synergies with medical products.

At that time, PGS was coined as “bio-rubber” because it’s a flexible elastomer that is bio-friendly and biodegrades; it’s soft, stretchy, and compliant and can mimic the mechanical properties of native tissues. There are advantages at the cellular level, in terms of mechanotransduction and biocompatibility, to a flexible material that can match the compliance of native tissues as opposed to the hard plastic common polymers currently in use.

Since then, Secant developed a variation on PGS with enhanced properties for improved processing and shelf-life storage called PGS urethane (PGSU), which comprises our Hydralese™ platform today.

Aside from having optimal and tunable mechanical properties, Hydralese is a biodegradable polymer that can slowly degrade in the body over the course of two months to two years — there simply aren’t viable options on the market that are both flexible and biodegradable like PGSU. Hydralese degrades through surface erosion as opposed to bulk degradation. Bulk degradation is the common breakdown process of commercialized biodegradable polymers. Other polymers don’t degrade at all and either reside as a permanent implant inside the body or require removal from the body at the end of treatment.

To paint a better picture, imagine bulk degradation as cereal sitting in milk; the material swells up and gets soggy before eventually falling apart into multiple pieces or a pulpy mass. Hydralese is more like a cough drop that slowly diminishes in size over time. It erodes primarily through the interaction with water, as well as with exposure to enzymes, cells, and biological fluids. This main mechanism of hydrolysis is very controllable and predictable.

When it breaks down, PGS is degraded back into its starting components — glycerol and sebacate — which then are metabolized by and even act as nutrients for cells. Hydralese fully bioerodes within the body through metabolism and excretion pathways. PGSU degradation does not exhibit the same acidity in the local tissue microenvironment as other biodegradable polymers. We’ve completed a lot of animal testing and comprehensive biocompatibility tests per ISO 10993 guidelines, which show that it’s a largely inert material and is thus very innocuous and safe. These same traits make Hydralese attractive from a drug product formulation standpoint, as it has a sustained drug release rate and allows a larger amount of drug to be delivered over a longer period, with greater linearity and control.  

DA: What can you share about the end-use applications that exist for Hydralese and any future uses that you anticipate?

SR: There’s a push to move away from animal-derived products in medical devices and to replace collagen or gelatin with a substitute material that is preferably synthetic. Our PGSU-based platform, Hydralese, has ideal elastic properties for devices that may require transcatheter deployment or may experience pulsatile or other mechanical forces at the anatomical site. In addition, Hydralese offers predictable and controllable degradation and the ability for ambient shelf-life storage, bypassing the need for fixatives and cold-chain storage and transport. This means a device could be stable at room temperature and humidity without requiring any formaldehydes or refrigeration, like animal products do to maintain their shelf-life.

Hydralese is a water-impermeable polymer, which enables it to surface erode — water can’t access the interior. This lends itself to application as a coating on medical devices and to make previously porous textiles water- or blood-tight. We’re working on many projects in the vascular device space using Hydralese as a blood-tight coating. The material itself is very hemocompatible, making it suitable for heart valve leaflets and vascular stent grafts.

We’re also highly focused on controlled release of pharmaceuticals using Hydralese implants, microspheres, coatings, films, and gastroretentive devices. One therapy area of interest is ocular drug delivery. In this end-use application, materials are either implanted or injected into the eye, so patient comfort and tolerability are paramount. Hydralese can deliver more drug over a longer period such that an injection could be spaced out from weekly to twice annually, which would be a tremendous advantage for patients. Secant is working to create solutions for retinal diseases, glaucoma, and other sorts of inflammatory issues in the eye to help realize this goal and advance these programs.

We’re also highly active in HIV prevention and treatment, as well as the co-delivery of HIV prophylactic agents alongside contraceptive agents. These dual-delivery strategies that simultaneously prevent the spread of infectious disease and prevent unwanted pregnancy using a single product are called “multipurpose prevention technologies.” There is understandably significant interest by non-profit and humanitarian organizations due to the enormous potential to impact global health, especially in areas that are challenged by access to healthcare.

Lastly, we’re working on sustained delivery solutions for neurodegenerative and neurological disorders, where patient non-compliance to their medication regimen is inherent to the disease, creating target end applications for diseases like Alzheimer’s, Parkinson’s, and schizophrenia. Compliance is one of our strongest drivers. Many studies report that, in the United States, non-adherence to medication is a $100 billion problem annually and a huge burden on the healthcare system, which ends up falling on the payers. Having solutions that can advance and promote greater public health overall is incredibly meaningful.

DA: What disciplines have to converge to facilitate development and manufacturing of such advanced biomaterials, and how challenging is it to assemble a team with the expertise needed to handle and advance these materials?

SR: Considering that the work we do is highly focused on biomaterial-tissue interactions, our people largely have deep expertise in polymer chemistry — but we need experts across disciplines, including expertise in analytical chemistry, formulation, pharmaceutics, process scale-up, immunology, biocompatibility, and hemodynamics. We’re seeking to onboard as much experience as possible within our strategic sectors and have been bringing on individuals with a diverse acumen, allowing us to take on a wider variety of projects.

DA: Beyond the evolving technology, have new offerings or services recently emerged at Secant?

SR: We’re moving fast here at Secant. We’ve recently brought in the capability to handle highly potent active pharmaceutical ingredients (HPAPIs), which require special safety equipment, such as the right glove boxes, a cleanroom environment, validated cleaning protocols, respiratory protection, and gowning.

Similarly, we’ve implemented pilot-scale equipment to translate what we’ve been doing on the bench with small-scale tools to a higher throughput system that demonstrates line-of-site to clinical and commercial scale manufacture. Our reaction injection molding system allows us to formulate and then fabricate 100 implants from a single shot of formulated material. With a well-designed setup, we can make up to 10,000 implants an hour. The reaction injection molding equipment works with many kilograms of material. We also have different molds that we can hook up to it so we can mold different sizes and shapes of drug-loaded Hydralese components.

We are also doubling the footprint of our headquarters in Telford, Pennsylvania, and adding in more clean rooms for medical device customers, a larger-capability cell culture lab, and more suites for compounding drug delivery products for pharma customers.

DA: How strong is the awareness in the pharma industry of the applications of this kind of technology?

SRWe have very strong interest from pharma right now and have been fortunate to have been speaking with a high volume of customers. It’s important to us to spend time exploring partnership opportunities, sharing data, discussing potential collaborations, and trying to see where a customer’s pipeline of APIs might fit in with our PGSU platform. Pharma customers that we engage with run the gamut from ophthalmology to neurology, oncology to diabetes, HIV/contraception to malaria/tuberculosis, and animal health. The interest is there, and we’ve been working on this platform for a few years. Our next step is to make those connections and anticipate where the partnerships will happen.

There is a lot of curiosity about implants, especially micro-scale implants and microspheres, as well as gastroretention devices. Though we’ve been delivering a lot of different small molecules, we’re constantly asked if Hydralese can deliver proteins, monoclonal antibodies, or smaller payloads like peptides. That’s the future of growth for us, to show biologic delivery beyond what we’ve demonstrated with small molecule delivery.

DA: Is the work you do with clients structured around longer-term strategic partnerships?

SR: Yes, although we do work within a variety of frameworks with clients. At the most fundamental level, we’ll take a client’s API and formulate it within our Hydralese polymer. We create implants, micro-implants, microspheres, gastroretentive rings, coatings, standalone devices, and fiber prototypes. Our clients come to us with their desired target product profiles, which we design against to meet all requirements. We basically create a whole data package, inclusive of physiochemical characterization and dissolution release kinetics around a variety of formulations, and share drug-loaded Hydralese prototypes with our customers before moving on to animal studies. We do a lot of heavy lifting early on to prove feasibility and offer the possibility to ultimately transfer the tech to our customers for later-stage clinical development and commercialization. We also provide technical, regulatory, and CMO support as desired.

DA: How is Secant positioned within the biomaterials landscape, and what are the true differentiators both in technology and as a broader business?

SR: When you look across the market of commercialized products that use different biomaterials, they fall into two main buckets. The first category is called bio-durables, which are non-degradable materials, such as polyurethane, thermoplastic polyurethane, silicone, and EVA. In the biodegradable space at the other end of the spectrum, natural biomaterials such as fibrin, collagen, and gelatin don’t last long enough for most long-acting pharmaceutical formulations and suffer from animal sourcing issues that impact medical devices. Synthetic biodegradables like PLGA and PCL are widely used in tissue engineering, medical device, and pharma, but there has been no new polymer offering in a couple decades.

While we’re not naïve and we understand the legacy of these materials, our offering comes with unique advantages. Those other materials are best likened to generics because they’re all non-proprietary and have existed for decades. Our PGSU polymer can give our partners a competitive advantage, a compelling marketing angle, and a patent life-cycle extension strategy, especially by having a novel, proprietary material like ours in their product offering.

DA: What other areas is Secant likely to move into, and how do you predict customer needs changing?

SR: I believe the industry is at an inflection point in that there’s a lot of new therapy areas and indications in which a long-acting solution can be transformative for the end-use of the patient. There are a lot of innovations going on in oncology, immunoinflammation, and diabetes management that need a platform or a carrier that could provide better release kinetics.

There aren’t any biodegradable long-acting implants on the market beyond micro-scale ocular products, so this appears to be a gap likely driven by current polymer choices being inadequate. We envision biodegradable Hydralese devices at a range of micro- to macro-sizes that can be administered through subcutaneous, intramuscular, intravascular, ocular, intravaginal, intrauterine, and gastrointestinal routes. Additionally, Hydralese broadens drug candidates considered for long-acting formulations beyond potent molecules into less potent molecules as well, by being able to load larger amounts of a drug into an implant yet still deliver the payload in a sustained manner. Another trend is the move from small to large molecules. There are new advances in orally bioavailable large molecule biologics, and gastrointestinal delivery using a gastroretentive Hydralese device is going to open a lot of doors.

DA: How do you think the market for these materials, both in devices and pharma, is going to change over the next decade? How do you envision Secant evolving, and what is the future vision for the company?

SR: Our goal is for the PGSU platform to be in human trials within the next few years and to be commercialized in 10 years. We know that the path to commercialization is long and that there’s a lot of attrition along the way, which is why we value the many partnerships in our pipeline. We’re hoping to move through clinical development with the intention that two or three winners will emerge. At present, we’re doing preclinical work, but we’re looking to support up through phase IIA clinical trials in the next several years. The market for long-acting offerings is growing into new therapy areas, and we want to be prepared to support it.

DA: Are there any regulatory challenges facing this technology?

SR: There are usable guidelines from the FDA and IPEC about novel excipients for the pharmaceutical industry. We are submitting a Type IV Drug Master File (DMF) for Hydralese as a novel excipient at the end of this year. Our DMF will be beneficial to reduce the regulatory hurdles our partners may face.

The typical approval pathway that we would most likely be seeking is the 505(b)(2) pathway, where a drug substance has already been commercialized in an oral solid dose and the safety and efficacy profiles are known. When the FDA reviews an IND submission or an NDA/BLA submission for a drug/biological product, they’re going to be looking at the drug-polymer interaction and referencing the polymer data package contained in the DMF, including the stability and toxicity. Similarly, for medical devices, the DMF can be referenced for its data contents regarding shelf-life and biocompatibility.

DA: When you look forward at the future of medicine, what do you think is going to be the next big thing?

SR: COVID-19 thrust mRNA vaccines into the limelight. Two big questions come into play. What else can mRNA medicines solve? And what polymer carriers can advance and accelerate those mRNA technologies? Beyond that, there’s a prevailing hope that allogenic and autologous cell therapy will gain traction and accelerate. While the cost and the manufacturing challenges associated with those cell therapies are quite big, I’m hoping that new advancements will reduce expenses and make those cell therapies more accessible to broader patient populations.

There are many techniques to make the processing of ex vivo cells more uniform, reliable, and efficient. Our research team is doing some work with PGS in that space to try to improve things like ex vivo cell selection, cell activation, and transfection, as steps in the CAR-T cell therapy process.

My background is in 3D printing. This technology raises a lot of curiosity about how it can be explored for a wide host of applications, given the geometric complexity and multi-material designs achievable using additive manufacturing. While I don’t believe the printer hardware and throughput is at the level needed to enact sweeping, cost-effective disruption yet, there is some great research and product development in the works to help remove those barriers.

Perhaps one of the most promising innovations for the industry is in dark data dives, in which AI is utilized to mine information on industry failures gathered by a plethora of companies over decades to see what can be learned.

In the same realm as data-driven approaches, patient-centric medicine and personalized medicine require greater focus. Diversity and representation are often lacking in clinical trials, as is having more of the patient’s own data driving the medicine and the doses that they receive. I think there’s a lot that can be done to achieve more inclusive and tailored public health approaches in that space.

Stephanie Reed, Ph.D.

Stephanie Reed, Ph.D., is the Director of Translational Product Development at Secant Group, a textiles and biomaterials company outside of Philadelphia. At Secant Group, Dr. Reed leads a team of scientists whose goal is to launch new biomaterial polymers for commercial use in controlled release drug products, biomedical devices, and tissue engineering applications. Dr. Reed garners 14-plus years of experience in drug delivery, biomaterials, 3D-printing technologies, regulatory submission, and product commercialization. Dr. Reed earned a BS in mechanical engineering at Massachusetts Institute of Technology, and an M.S. and Ph.D. in biomedical engineering at University of California Los Angeles.