Demand for nanoparticles in the biopharmaceutical industry is on the rise. Production of these tiny particles, which can protect and deliver medicines and vaccines where they need to go in the body, has been increasing since 1989. Over the last two decades, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved nearly 80 products involving nanoparticles, according to a 2022 report in Pharmaceutics. BCC research estimates that the global market for nanoparticles in biotechnology, drug development and drug delivery will reach $123.6 billion by 2025, up from $83.4 billion in 2020.
Daniel Callahan, Lead Scientist, Drug Product Development at Emergent, says he’s seen that surge first-hand. “We’ve seen increased demand for development and manufacturing support for nanoparticle products in the past two years,” he says, pointing to examples such as therapeutics or vaccines that include RNA or DNA and enhance the immune response by incorporating the antigen in nanoparticle form.
Callahan attributes the recent increase, in part, to advances in the science, technology and application of nanoparticles. “What once sounded like a pie-in-the-sky idea decades ago—bringing a nanoparticle product to market—now is reality,” he says. “Because it’s been done before.”
And, of course, since 2020, nanoparticles have achieved a sort of celebrity status, thanks to the role they’ve played in Covid-19 vaccines, including those made by Pfizer and BioNtech, Moderna and Novavax. “For people working on nanoparticle technologies or trying to make the case to their management, those were very public, salient examples of how nanoparticles can be a big benefit,” says Callahan.
As more biopharmaceutical organizations consider using nano-based systems in therapeutic formulations, there are pros and cons to consider, says Callahan. He shared insights on the benefits and challenges of working with nanoparticles and emphasized the importance of collaborating with a trusted partner who can provide equipment and expertise.
The benefits of nanoparticles in drug formulation
When Callahan considers the potential of nanoparticles, it thrills him as a scientist. “Not only can we work on developing new drugs and new vaccines, but we can also develop new materials to control how those drugs and vaccines are trafficked through and interact with the body,” he says. “It opens up a whole field of possibilities.”
Nano-based systems are attractive for a number of reasons, says Callahan. First, he says, is the ability of nanoparticles to protect active pharmaceutical ingredients from degrading both in storage and while being transported in the body. Second, there’s the “biodistribution” component: nanoparticles manage where the drug accumulates in the body and how long it circulates before it’s eliminated. And third, he adds, nanoparticles can change how the drug interacts with the cells at the target site.
To illustrate some of those benefits, he shares the example of an RNA or DNA vaccine: The RNA or DNA typically needs to be delivered inside of the target cell, or in the nucleus of the target cell. Nanoparticles protect and deliver. “Nanoparticles are really important for providing protection of the genetic payload from enzymatic or other degradation in the body before it can reach the target site,” he says. “And then the nanoparticles are also typically engineered to facilitate entry into the cell, followed by a release of the genetic payload inside the target cell.”
Challenges in nanoparticle production
Because of its highly specialized nature, nanoparticle production is complex. A variety of technologies and techniques are required to design the different types of nanoparticle “vehicles,” for example. Specialized equipment, such as microfluidic mixers and extruders might be needed, says Callahan. And expertise is critical. “In nanoparticle manufacturing, we are mixing multiple components and they have to be mixed under tightly controlled conditions in order to obtain the desired nanoparticles,” he says. Controlling the encapsulation process, for example, as well as the size of the nanoparticle, is crucial in achieving the sought-after biological effect. And it’s also a regulatory concern: “Regulators want to see a well-controlled size distribution,” says Callahan.
Further, it’s important to design a mixing process that can be performed at scale to deliver nanoparticles with those same consistent characteristics such as size and encapsulation. Because nanoparticle production steps may take long periods of time, Callahan says the stability of both the feedstocks and the nanoparticle is critical. The stability profile of the final product can also present challenges: not all nanoparticles exhibit sufficient stability in liquid form, but the formulation must be carefully developed to maintain the target particle size during stabilization by freezing or lyophilization.
And, of course, it’s essential to add that every formulation is temperamental—and different from the next. “The conditions that affect nanoparticle formation are highly sensitive to the exact molecules that are being mixed,” says Callahan. “There's a lot of variables and you need to go through the development process to understand how to set those variables in the right place each time.”
The importance of partnering with a CDMO
Collaborating with an experienced partner, such as a Contract Development & Manufacturing Organization (CDMO), could prove to be invaluable in developing nano-based systems, says Callahan. “Those experts can foresee and address the potential pitfalls,” he says. “A CDMO with experience in this area will be able to assist with selecting appropriate manufacturing equipment for the nanoparticle under development and consider how to convert that into a process that can be executed under Good Manufacturing Process (GMP) conditions.”
He adds that a CDMO should be able to explore and develop the process parameters that control the nanoparticle formation and ensure that those parameters are under sufficient control, so that each batch of nanoparticles meets the same product quality criteria. A CDMO also can help select the product presentation to address any stability concerns, whether through a liquid formulation, frozen storage, or lyophilization.
The bottom line is this: experience matters.
“You really want to be working with a partner who has done this before, because implementing a nanoparticle manufacturing process is not trivial,” says Callahan. “People who have done it before will have learned a lot of lessons and can apply that to your project. A CDMO should be able to foresee those common pitfalls and challenges and address them proactively.”
To learn more about nanoparticle capabilities, visit Emergent CDMO.