In order to gain more insights about the trends and challenges affecting the diverse drug delivery and combination products markets, I spoke to James Arps, Ph.D., director of pharma services at ProMed Pharma LLC, a Minneapolis, Minn.-based contract manufacturer of polymer-based drug releasing molded dosage forms and combination device components. A portion of his input was included in the November/December issue feature article “Delivering the Goods: The Evolving World of Combination Products.” The entirety of our interview is featured here.
Sam Brusco: What were the trends that drove the biopharma and drug delivery/combination product markets in 2019?
James Arps, Ph.D.: We focus on sustained release complex dosage forms and drug/device combination products, essentially, we’re looking at ways to keep from forcing patients to take a daily pill or visit the clinic for a weekly or monthly injection. Patients simply don’t want to do these things, which impacts how well the therapy works.
The industry has been focusing more on sustained release applications due to the rise of some innovative technologies. For example, a company has developed a novel once-a-month pill that utilizes an interesting polymer drug release technology for a number of applications.
We also notice significant interest in pain management alternatives due to the opioid crisis. We’ve seen neurostimulation devices that mask the pain by stimulating the spinal cord, as well as sustained release, non-opioid drug-eluting implants that deliver locally to the region of the pain. These technologies have been used for applications like treating post-knee-surgery pain and sciatic nerve-based lower back pain.
Brusco: Which latest developments and/or innovations in drug delivery technology/combination products have captured your attention?
Dr. Arps: A particular class of drug delivery technologies involves sustained release, long-acting implants implanted underneath the skin. These have a long history, particularly in the area of contraception. Most of these are composed of durable polymers like silicones or ethylene vinyl acetate.
The preferred approach to using these devices is a low-effort one: implant it, have it release the drug, then it will slowly dissolve away so you never have to worry about taking it out. And if you want a new one implanted after a year or two, that can be done. Unfortunately, the number of resorbable polymers on the market has been limited, and these polymers don’t always have the best properties for the application.
We’re working with a couple of companies with new polymer technologies that are much more effective for sustained release. These polymers maintain mechanical integrity over a longer period of time and slowly dissolve away like a bar of soap while the drug is released. For example, we have a public strategic partnership with DSM Biomedical, who has developed a polymer called polyester amide (PEA) that has some novel resorption properties.
Brusco: What effect is the convergence of pharma and medtech having on the medical device industry?
Dr. Arps: From a regulatory standpoint, the medtech-pharma convergence is evident simply because it’s a combination product. In the U.S., the FDA’s Office of Combination Products regulates these technologies. This office pulls in people from both the pharma and medical device regulatory groups. Because of that convergence, pharma has recruited quality personnel associated with the medical device industry. It is important to have this perspective because the pharma industry hasn’t previously had to deal with medical device regulatory constraints like design master files.
The medical device side has to engage higher levels of pharma requirements like data integrity. When testing combination products, how data is managed, maintained, and protected for both development and the commercial manufacture is crucial. FDA is also paying more attention to how we manage and approve suppliers to ensure components going into drug-device combination products are high-quality and appropriately controlled.
Brusco: How does the approach to designing, manufacturing, and/or testing a drug delivery device/combination product (or components that go into these devices) differ from other medtech products?
Dr. Arps: Quality by design is a huge buzzword in the pharma world, and that is starting to migrate more into the medical device world. It’s important to lay out the target product profile andthe critical quality attributes of the product we’re developing with our partners. Trying to draft process FMEAs early on, and anticipate where the potential bottlenecks and challenges will be.
The other piece with a combination product is a lot of analytical testing to characterize how the drug comes out of it, and if any of the processing of the drug into the device can degrade the drug at all. We have an in-house analytical lab with a lot of experience specific to some of these long-acting implants and combination products, so we can very quickly develop and test new formulations. We have a good efficiency backloop on that.
Brusco: What are the challenges and opportunities for drug delivery and combination products in the next few years?
Dr. Arps: Everyone has their own particular “mousetrap” and a way of doing things. We want to be able to tailor our solutions to the particular customer’s needs and to come up with an efficient development and manufacturing timeline for them. Speed to market is still a huge consideration, and part of that is speed to clinical trial. Once a decision is made that you’re happy with this formulation, you must move as quickly as possible to get into clinical studies with the appropriate safety profile, and have all the details worked out at the appropriate time.
Brusco: Is there anything else you’d like to say regarding the manufacturing of drug delivery/combination products or components?
Dr. Arps: When trying to establish a partnership with a company in this field, look at their background and experience. We have a history of manufacturing these products—to our knowledge we were the first contract manufacturer to make drug-device combination component like steroid-eluting leadss for cardiac pacing. We were the first one in the U.S. to really establish that—before, it was all the final device manufacturer. Being the first contract manufacturer with the quality systems and manufacturing processes in place to handle these was key.
We’ve also embraced having experience with a wide range of polymers and active pharmaceutical ingredients for drug delivery because the various drugs interact differently with each polymer. That background experience has been helpful to moving development forward as quickly as possible.