November 22, 2021 PAO-11-21-CL-13
BG: Yes, because nobody wants to be the first one through the wall. The FDA can continue to be more forward-leaning, but not at the sake of safety. However, in analogous industries, they look at data, prevalence, and history to make calculated safe bets, which seems to be the direction that the agency is headed with some of the pilot programs it is running.
BG: I think there will always be space for a variety of approaches. Oral solid delivery is king, because it’s relatively easy to manufacture, offers tremendous yields, and has a much lower cost of development. With more complex systems like injectables, even sterile filling, once you have the facility, it’s a very predictable process. However, in addition to undoubtedly being the least favored dosage form, parenterals present refrigeration challenges that become especially exacerbated when dealing with worldwide distribution.
The pandemic has reignited interest in niche delivery systems like the microneedle. While the microneedle has an over 30-year history, it’s often batch-oriented instead of being mass produced, which has made it cost-prohibitive. Despite this, it is a viable option for bypassing cold-chain issues.
We have a development partner on the leading edge of roll-to-roll or taking a rolled good in raw material form and manufacturing that to a microneedle array at scale. It can be used as a dermis preparation, in which the dermis is first abraded, then the patch is applied, and, because the skin has been prepped a bit, more API can cross the barrier. Of course, the body eventually heals and closes the abrasion as interstitial fluid comes up and blocks the active.
Our development partner 10X Technology will likely take the next step forward, which will be reliably producing a hollow microneedle system at a much lower cost than ever seen before and at scale. This will be a massive gamechanger that eliminates expense issues and can be taken to parts of the world that haven’t been able to accommodate most vaccines. This is part of our MacroDerm brand in partnership with 10X.
BG: I’m biased in that I believe the real work that needs to be done is in the scale-up and controlled replication toward commercialization of the concepts. Though it’s possible to produce an innovation either in handmade parts or small batch quantities, being able to develop it into a repeatable and controllable process for a reasonable cost is the real limitation — not being a commercially viable concept is often a cause of failure.
BG: It’s compound-dependent; although it won’t replace everything, it will open up new options for treatments and vaccines that the developing world has historically lacked compared with developed countries. There’s a need for drugs to be more portable and stable so they can be distributed, stored, and ultimately administered in harsh, remote, and/or hot environments. Alternative delivery systems like transdermals could be leveraged as a solution and as a key tool for the military, hospitals, and remote communities.
Especially with pediatrics: it’s a fact that kids do not like needles. Abrading the skin and then applying a transdermal, particularly if you’re a parent administering a drug at home, is a better, more patient-centric choice than an injectable. I’m confident that, in the next 5–10 years, there will be innovations to come out of this space that will solve the inherent problems that both temperature control and injections have presented for many patient populations.
BG: MacroDerm is our alliance with 10X Technology. MicroPerm is another strategic partnership with Biotts, a Polish-based R&D company that specializes in various permeation-enhanced delivery systems. Biotts’ patented delivery system can potentially deliver compounds as large as 26,000 daltons. To put that in perspective, that’s nearly 8–10 times larger than most small molecule compounds that can penetrate the dermis in a meaningfully bioavailable way. Outside of working with us, they have several different programs that are in development. If those prove effective, it’s another major disrupter, as it will allow previously non-viable compounds to permeate through an enhanced system.
This technology is highly proprietary, but an advantage of our strategic partnership is that our clients are given access to it. This is the primary reason we have been selectively looking to add partnerships in our portfolio with other companies that have patent-protected technology that lends well to transdermals or thin films, enabling us to offer our clients more tools and options.
BG: Depending on the compound, the mucosal lining of the mouth can be 4,000 times more permeable than the skin. This means that, on average, targeting the mouth will lead to more success. Despite this, transdermal activity has prevailed over thin film due to deep IP protection put in place by companies that entered into film early.
Those patents are just now falling, which has resulted in a surge of interest in thin film products, whereas four years ago the focus was on transdermal. I predict that the film world will explode in the next three to five years, particularly via 505(b)(2). Like transdermals, film can solve problems related to adherence, as it’s a lot more palatable than swallowing an oral solid for many patients, young and old.
BG: Polymers and various substances can be used to generate a slower release in thin film. One of the pressing problems in oral solid drug development is a spike in the therapeutic window where the amount of drug rises — which increases side effects — and then relatively quickly efficacy wanes on the back end. If the therapeutic curve can be made both flatter and wider, then you’ll typically reduce side effects and improve the safety profile, which is always the first thing the FDA looks at in any drug program. Transdermals lend well to making drugs more efficacious and safer for the patient.
BG: As Tapemark’s brand equity has continued to grow along with the strength of our reputation, the more our prospects have increased, which equates to greater quality programs signed as a result of our thorough vetting process. As soon as a lead comes in, we question if we’re the best organization for that client — we reject business if it’s not the right fit for both parties. Although we’re not the largest CDMO, we’re the most premium, hands-on, and accessible company in the space.
We take our time to ensure that the relationship will succeed from the start by asking, do we have the competency to accomplish the goal, and is the concept right for our delivery systems? We also consider the client and their track record of success, experience, and overall business plan, finding out if they want to go to market through their own sales force or license or sell the asset? If that’s the case, we find out if they have already identified a future partner, as well as a lot of other key items related to their plan.
BG: Our scientists want to take on interesting and complex challenges they haven’t before — as long as they’re feasible. There are many instances in which a great idea lacks commercial viability. When we see unique assets, we can arrange to waive or discount the fee-for-service in exchange for part ownership, which can be an ideal arrangement for some prospects. Of course, we also offer traditional fee-for-service relationships.
We’re constantly on the lookout for the former. It can help ease the client’s need for capital and create an ideal synergy when a CDMO has a vested interest in the asset. Though these clients don’t receive more attention than our fee-for-service partners, it adds a different element to the relationship. They realize we aren’t making money on the platform in development — we want to find technology that works, even if it may not pay off for another three to five years.
BG: Our customers range from the largest pharmaceutical companies and generic manufacturers to virtual organizations consisting of two employees. The common element between our clients is the desire for premium service and accessibility. I share my personal phone number with clients, which is unheard of at other CDMOs but demonstrative of how Tapemark operates. Above all, trust is a key factor in a great partnership, too.
BG: Iontophoresis has been around for a long time — it’s typically referred to as “box and wires.” A patient will be hooked up to a device that plugs into a wall outlet with leads placed on various body parts to apply iontophoretic stimulation. This is a very low-level voltage that typically drives a compound across the dermis into the body, usually for local delivery.
IontoPatch is a completely self-contained Iontophoresis system, where you have a patch and a very thin lithium battery connected to positive and negative leads; all the circuitry is contained within the patch. It has almost no feel and can be placed anywhere on the body, so the wearability is also discreet for the patient. It’s traditionally been used to deliver things like dexamethasone, which is a type of steroid, or diclofenac, a nonsteroidal anti-inflammatory drug, although their use is not predicated nor required by our product label.
The IontoPatch is a 510(k), meaning it’s a type II medical device and not a drug combination. If a patient has a prescription from their healthcare provider, they can prescribe the active along with the recommendation for IontoPatch as the delivery system. There’s a new area of interest, particularly with IontoPatch in NAD, for its use in skin clinics to reduce the effects of aging. This technology is also attractive for the micronization of CBD. IontoPatch opens up a host of possibilities to deliver products in an entirely new way, which also extends to non-opioid and non-addictive pain relief options for the patient.
BG: Particularly with microneedles, there will be smarter systems that feature an integrated digital element. That digital technology may not necessarily have anything to do with delivering the drug, but everything to do with interacting with the patient and monitoring their systems, including how the transdermal is performing. Before long, it will be clear how much drug has penetrated the skin versus how much remains in the patch.
This will be integrated with devices that interface with the patient to check symptomology. In certain chronic diseases like respiratory illness and cardiovascular diseases, there is often a warning sign that a patient is worsening and is likely to end up in the ER, because they have an event like an exacerbation in COPD (chronic obstructive pulmonary disease) or a TIA (transient ischemic attack) in patients with ischemic disease, which is obviously very costly to the patient, employer, Medicare, and/or health system. These warning signs of a patient’s disease worsening could be preventable through a real-time smart system that’s funneled into the cloud and can be accessed by the caregiver, enabling a potentially lifesaving intervention. I’m confident this will be available in the next 10–15 years. Transdermals fit perfectly into this future reality, as they are a physical medium that supports a range of circuitry without an exorbitant cost.
As Sr. Vice President & Chief Operating Officer at Tapemark™, Beau Garrett has nearly 20 years of pharmaceutical expertise and thoroughly understands the needs of the pharmaceutical maker. He understands the value and innovation created by pharmaceutical therapies administered by the United States’ most complex integrated healthcare systems. Beau has experience with more than two- dozen therapeutic areas, has sold and marketed 14 branded therapies, and has launched 6 NDAs of which 4 became blockbuster products. Beau received his undergraduate degree in economics from The Colorado College and completed his MBA while attending The Carlson School of Management and The Gore School of Business.