Delivering Success — The Importance of Considering Drug Delivery Early
As chronic diseases rise globally, the bio/pharma industry is pivoting toward increasingly complex molecules that demand more sophisticated delivery strategies, which must be considered early on in development.
In order to respond to the rising prevalence of chronic diseases worldwide, it has been necessary for the bio/pharmaceutical industry to innovate across the whole development lifecycle — from discovery through to formulation and manufacturing. As more complex molecules are investigated for their therapeutic benefits, industry has been pivoting to the challenges these present by employing new strategies and making use of advanced technologies.
A key area that has required attention and innovation from industry has been the delivery of these therapies. According to market research, innovation is central to the drug delivery market, with companies focusing on patient-centric, precise, and minimally invasive drug delivery solutions (1).
However, many innovator companies do not have the expertise, capacity, or capabilities in-house to be able to manage the delivery of their valuable drug products effectively and, therefore, need to lean on service-providers for these increasingly intricate tasks.
Click above to watch a video interview with multiple subject matter experts or read on for more…
Focus on Topical and Transdermal Delivery
A Shift to More Integrated Partnerships
“Historically, there were CMOs, that were focused on later-stage scale-up and manufacturing, whereas the CROs handled the kind of more early-stage formulation design and any in vitro/ex vivo models,” remarks Charles Evans, Senior Vice President of Pharmaceutical Development at MedPharm. “There has been a growing trend where that model has shifted to more integrated partnerships which keep things at ling of a one-stop-shop in-house, and that reduces tech transfer risks and can help accelerate timelines.”
Additionally, Evans adds, when molecular complexity of the drug product increases being able to work with a singular provider, in a one-stop-shop, that can take the product all the way through the development lifecycle can help reduce risk. “However, I think it’s very important to point out that this solution only really works when CDMOs truly have development experience, and not just manufacturing, especially when you’re looking at the more complex routes,” he says.
Traditionally, CMOs have focused on the manufacture rather than optimization of the drug product for delivery, so, there are some key questions that innovators need to ask to ensure that their prospective partner really understands early-stage development, Evans stresses.
“Skipping the formulation development phase is definitely a false economy,” Evans cautions. “You can run into issues later on in the development cycle because with these more complex delivery routes, the formulation plays a critical role in delivering the drug.”
Adding to Evans’ comments, Jon Lenn, Chief Scientific Officer, MedPharm, highlights the apparent underappreciation of how complex topical formulations are, specifying that there is a temptation to skip the formulation development phase in order to accelerate timelines and cut costs. “When you shortcut the process and skip out on that pre-formulation step, you don’t really have that foundation or that baseline information on your formulation,” he says.
“There’s this false sense that you can potentially get to the clinic faster, which, maybe you can,” Lenn adds. “But we’ve seen a lot of clients start to fail on the formulation side, even in the clinic, which is not the phase of development that you want to start seeing these issues.”
If the critical early phase has been skipped, then the basic understanding of the physical and chemical stability of the compound within the complex formulations is missing, and there is no data to refer to when things go wrong, Lenn asserts. “So, you’re troubleshooting and backfilling at the same time, which then can lead into additional studies on the safety side, and then you have to get into this complex discussion of how you bridge it, and how you don’t bridge it,” he states.
Unfortunately, these sorts of “rescue programs” are not uncommon and have led to investment hesitancy within the topical space as a result of the potential for failure simply from skipping basic science, Lenn comments. “So, I couldn’t stress enough really, just spend the extra time [early on], your overall timeline will be shorter when you do it, and troubleshooting will be easier,” he says. “The majority of your problems are going to be from the formulation side, so, you’ve got to spend that upfront time in understanding the compound and its interaction with these different excipients.”
Balancing Performance with Usability
“Patient compliance has always been a pretty big issue, and if you think about it, there is an interaction with the product that occurs, especially when it’s more of a chronic condition, where you’re having to potentially do something daily over long periods of time,” Lenn remarks. “This is where ‘cosmetic elegance’ needs to come into play.”
It is critical to consider the patient in addition to considering the drug, delivery route, regulatory risk, and later-stage commercial aspects, Evans asserts. “So, it’s important to outline your target product profile (TPP) early,” he notes.
During the design process, it is possible to gain an understanding of how easy it might be to match all the aspects set out in the TPP, Evans continues. Performance models can also be leveraged early on to gain an understanding of what excipients may be required to not only achieve cosmetic appeal, but to also be able to deliver the drug effectively, he adds.
“The other thing to consider is that the skin is one thing, but if you’re applying topically to the eye, or anything like that, you need to consider the packaging and how that’s going to be used,” Evans specifies. “Then you’re looking at patient usability as well as cosmetic appeal. So, I think everything kind of comes together and you need to consider all aspect, not just cosmetic appeal.”
De-Risking Development
When looking at topical and transdermal formulations, developers are at an advantage in that they can potentially have direct access to the organ they are trying to target, Lenn points out. However, it is critical to understand the nuances of in vitro and ex vivo models to ensure you optimize results.
According to Lenn, these models can be broken down into three main categories: early models where the release of the compound is assessed; later stage models to evaluate product quality; and then delivery models that allow insight into penetration and permeation. “I think, it’s really key to stay away from animal tissue and frozen tissue,” he states.
“There are some animal models that claim they are closer to humans, but just think of it as a general species, that they are close but not the same. So, I would avoid those unless you have some sort of safety question to answer,” Lenn adds. “Stick with human tissue but avoid frozen and thawed skin or tissue as much as you can [as] what ends up happening is when you go through that freeze-thaw cycle, you can damage those tight junctions, and the tissue effectively becomes leaky.”
While these models are useful, they are also not without limitations, Lenn warns. “There’s no perfect model out there that will answer pre-clinically what you’re going to see in the clinic,” he says. “What you want to do is de-risk that formulation from a release, from a delivery, and then from an activity standpoint.”
However, these models are beneficial for “de-risking your wallet,” exclaims Evans. The models can help with costs as they enable developers to understand the role of the excipient and how it can deliver the drug in greater detail, which in turn can then be used to support the generation of intellectual property (IP), he adds. “So, the models are multifaceted,” Evans specifies, “they are helping to de-risk going to the clinic but also helping to support in terms of IP generation.”
Focus on Drug Delivery Systems
Initial Design Strategy
When approaching the route of delivery for a drug product, the first consideration needs to be the properties of the drug. “Whether the drug will be destroyed in the gut, so cannot be an oral tablet, whether it is targeting the lungs, so may be inhaled, or whether it requires systemic delivery, so might be injected,” comments Iain Simpson, Director, Commercial Pharma Segment Team at Phillips Medisize.
After that, when looking at an administration route that requires a delivery device, the conversation moves to the requirements of the device, Simpson continues. Considerations for the device could be the volume of the drug to be delivered, the required speed of the delivery, whether or not the delivery needs to be continuous, and so on, he remarks.
“These considerations will then start to drive the choice of device type, which then takes you into the point about patient centricity,” Simpson remarks. “You obviously want to consider, you know, what works for the patient. Is that something they can use with relatively low burden in a home environment? Are they going to administer themselves, or is a caregiver going to give that for them?”
The last point to think about for drug delivery relates to the business case, Simpson asserts. For this, companies need to evaluate whether or not the delivery of the drug will be affordable or whether it will allow them to be differentiated from their competitors, and so forth.
“In reality, all the aforementioned things are intertwined,” Simpson notes. “A key thing that the pharma industry has learned is to think about drug delivery systems early. So, don’t develop your drug and then decide how you’re going to deliver it and what device you need to have, start thinking early about delivery options and the business requirements around that.”
Benefits of Pre-Vetted Platforms
When developing a new drug delivery device, companies are faced with risks, both in terms of time and cost from a technical and regulatory perspective, Simpson reveals. “So, there's no doubt, from a risk perspective, the use of a platform that's already been developed and approved for other medicines, is advantageous,” he says.
There are benefits for pharma companies to assess the device technologies early on using a platform solution, Simpson adds. “So, the companies will do some testing before they actually think about putting a molecule in there to build confidence that they have the right drug delivery tool in their box,” he states.
“I think the challenge is that the requirements for drug delivery are changing all the time, there’s uncertainties there around the volume or the viscosity of the drug,” Simpson continues. “So, you want to try and do some pre-work so you don’t have a problem suddenly that you find that the devices are no longer suitable for the way your formulations ended up.”
Increasing Dose Size
As complex biologics become more prevalent and demand for lower treatment burden continues to rise, the boundaries of volume and viscosities of doses are being pushed. This, points out Simpson, is very pertinent for the self-administration market over the coming years.
“Doses are getting less frequent and, therefore, bigger in size,” Simpson says. “This trend produces a dilemma: in order to increase a dose, you either have to increase the volume or increase the concentration of the dose.”
If the choice is to increase the volume, then there will be a point where an auto-injector cannot be used, leading to the larger volume devices, such as wearable pump technologies, Simpson explains. “However, if you want to stay within the autoinjector space — a well-trodden and well-proven market — then you’re obviously going up in concentration, which typically means going up in viscosity,” he notes.
“Going up in viscosity will mean two challenges in terms of drug delivery,” Simpson continues. “The delivery will require higher delivery forces, requiring technology that is able to support those higher injection forces such as electromechanical technology, and then there are challenges around processing and filling of the syringes that will go into the devices.”
Therefore, pretty radical adjustments are required for both the preparation and delivery of such drugs, Simpson remarks. However, the benefit of persisting with these necessary changes for auto-injectors is that the device format is well-established, he specifies.
Connecting Devices into a Digital Service
All the efforts in ensuring the delivery of the drug product is optimized are wasted, however, if the patient does not adhere to the treatment regime. To find a way to better support the patient and improve non-adherence rates, connected devices are being investigated, Simpson reveals.
“So, the idea of connecting a device into a digital service can do a number of things: it can provide the patient with direct feedback, training and support, and guidance; it can motivate them to take their medicine when they're struggling with that for whatever reason; and it can also share that information with other people, whether that's a caregiver or a healthcare professional,” Simpson says. Through these actions, it is possible to provide a more supportive environment for the patient to take their medicine correctly and, ultimately, manage their disease, he asserts.
While there are many benefits, there are also challenges with connected devices, Simpson iterates. One challenge relates to the patient’s behavioral change, leading to non-adherence, he notes.
“Sometimes people just don’t have the information to support their treatment, but other times they may be in denial about the disease, or they may be worried about the side effects of the drug,” Simpson adds. “So, the point is, if you have a connected device, you know when the person has taken their medicine or not, and then you can provide more tailored services to support that.”
Another potential challenge with connected and digital services for drug delivery relates to regulations. Companies developing a connected drug delivery device can face regulatory scrutiny over the drug itself, the delivery device, and then the digital service as well, he emphasizes.
“So, the challenge for pharma companies is yet more regulatory burden when they’re trying to get medicines to market,” Simpson stresses. “And, while there’s reasonable evidence that digital services can work and provide positive feedback, it is quite difficult to show that at scale.”
Looking a little more broadly too, the arrival of the MDR in Europe has also created further complexity and uncertainty for drug delivery devices. However, it isn’t all doom and gloom, there is a lot that can be done at the industry level to try to understand the regulatory landscape better, lower the potential burden, and establish the benefit of companion digital services, Simpson adds.
“There is some great work being done by industry collaborative groups that are exploring what the barriers are and how they can be best addressed at an industry level to make it easier than on an individual product level to get new devices developed and approved,” he affirmed.
Reference
Precedence Research. Pharmaceutical Drug Delivery Market Size, Share, and Trends 2025 to 2034. Market Research Report, Nov. 10, 2025.
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