Estimated at a value of $270 billion in 2023, the global drug delivery devices market is expected to grow at a compound annual growth rate (CAGR) of 5.83%, reaching about $403 billion by 2030, according to Grand View Research. “Increasing adoption of advanced technology for effectively delivering drugs on the target site is expected to drive the overall market growth,” according to the report.¹

Major categories for drug delivery include cardiovascular, oncology, neurology, infectious diseases, respiratory, diabetes, and autoimmune diseases. Oncology holds a significant share of the market; so do central nervous system disorders, which are estimated to grow at a CAGR of 6.6% over the forecast period, due mostly to the increase in neurological disorders such as Parkinson’s, Alzheimer’s disease, and other central nervous system conditions.¹

With these various segments all hoping to score the next breakthrough, the drug delivery industry is a highly competitive market, “with pharmaceutical companies vying for an edge in delivery methodologies to align with patient preferences and yield billion-dollar outcomes,” said Ned Burnett, strategy and innovation manager for Saint-Gobain Medical, a Solon, Ohio-based manufacturer of high-performance polymer solutions and components for the medical device industry. “Similarly, for device manufacturers, being included in a patient’s preferred route of administration holds immense volume prospects, making the industry highly competitive from both angles.”

“Numerous companies are striving to develop novel products that address unmet medical needs and improve patient outcomes,” added Rory O’Keeffe, commercial director for Europlaz Technologies, an Essex, U.K.-based provider of engineering and manufacturing services for the medical device industry. “Collaboration between pharmaceutical and medical device companies is becoming increasingly common as they work together to create integrated solutions for healthcare delivery—especially combination products.”

To leverage each other’s specialties and markets, pharma companies and contract development and manufacturing organizations (CDMOs) have undergone consolidation in recent years, such as Novo Nordisk’s pending acquisition of Catalent, a major CDMO—in part to ensure sufficient future manufacturing capacity for two major diabetes and weight loss products, Ozempic and Wegovy.

“Industry cycles follow the R&D budgets of big pharma and venture capital investments in earlier-stage pharma companies,” said James Arps, director of pharma services for ProMed Pharma, a Plymouth, Minn.-based provider of injection molding and hot melt extrusion of drug-loaded silicones and thermoplastics for delivery systems and combination devices. “Companies that specialize in relatively unique offerings such as long-acting dosage forms and implantable combination products may see relatively less competition.”

Latest Trends

Many drug delivery manufacturers are focused on finding solutions for unmet needs, in part because it is easier to become a leader in a market segment that has less competition. These companies are focused on making the patient experience a top priority with novel drug delivery systems that are more precise and efficient as well as easier and more comfortable to use. For example, “right now there is significant emphasis on precise delivery—targeting different areas of the body than we have in the past, such as new and more accurate inhalation devices,” said Katlin Lumme, director of engineering for life sciences for Porex Filtration Group, a Fairburn, Ga.-based provider of high-value solutions for drug delivery systems, including absorption, application, diffusion, filtration, venting, and wicking.

Drug delivery manufacturers are also expanding the variety of delivery methods to satisfy a wider range of patient preferences, including ease of use and less pain. “Possessing a drug asset that has multiple administration routes can significantly enhance the value proposition for pharmaceutical companies and patients alike,” said Burnett. “Consequently, we observe a movement toward utilizing previously underexplored administration routes within specific product categories. For instance, there’s a notable shift towards administering oncology assets subcutaneously and incorporating wearable injectors into immunology treatments.”

Not only do combination products require optimized formulations for therapeutic efficacy, they also need new-generation injections that utilize high-precision delivery technologies, clean container closure systems, and sustainable, patient-centric methods of delivery.

“For a combination product, it is imperative that the delivery of the drug is optimized for consistent pharmacokinetics thus resulting in successful clinical outcomes,” said Asmita Khanolkar, senior director for SMC Pharmaceutical Services, a Somerset, Wis.-based contract development and manufacturing organization (CDMO) with expertise in drug delivery devices and combination products. “SMC has developed methodology to characterize the formulation, injection site, and tissue response and optimize for therapeutic efficacy. Patient experience and rapid manufacturing scale-up are two other critical considerations while developing novel combination products.”

One of the best ways to improve patient quality of life is through the use of implantable drug delivery devices that provide sustained release of medications over extended periods, improving patient compliance and treatment outcomes. “These products, including drug-eluting implants, which can be made from biodegradable and bioresorbable materials, reduce the need for additional surgeries for removal,” said O’Keeffe.

Other trends that simplify and personalize medical care include less-invasive microneedle patches and inhalable drugs, which enhance patient comfort and convenience, and smart drug delivery systems, which integrate sensors and microprocessors into drug delivery devices, enabling real-time monitoring and personalized dosing programs. Specialty smart injectors and wearable drug delivery systems in particular are attracting plenty of attention. “We’re seeing a number of innovative drug delivery systems in the ophthalmology space,” said Arps. “For example, intravitreal injections for treatment of retinal diseases are gaining acceptance; however, the sheer number of potential patients seeking this treatment could overwhelm ophthalmologist practices—thus creating a real need for longer-acting drug delivery solutions that would reduce the frequency of office visits.”

What MDMs Want

Medical device manufacturers (MDM) are intent on developing user-friendly drug delivery devices that are easy for healthcare providers and patients to use, thereby promoting adherence to treatment regimens and improving patient outcomes. They also want quality and innovation at a lower cost, all while improving the patient experience and health outcomes. This can be accomplished through innovative product design, choice of materials, and streamlining the regulatory process.

For example, a regulatory challenge that many MDMs face is the growing emphasis on PFAS-free (per- or poly-fluoroalkyl substances) materials. As concerns grow about the environmental and health impacts of PFAS, regulatory bodies around the world are increasingly scrutinizing the use of these substances in medical devices, including drug delivery products.

“Consequently, Porex is investing heavily in research and development to produce alternative materials that comply with these regulatory requirements, while ensuring the safety and efficacy in drug delivery applications,” said Lumme. “This shift toward PFAS-free materials—especially as related to hydrophobic membranes—reflects the broader industry shift toward safer and more environmentally friendly drug-delivery alternatives.”

Sometimes the design changes simply improve patient and provider convenience—such as reducing the number of steps in a delivery process of injectables by removing the need for an accredited medical professional to deliver the drugs, “ultimately making it more user-friendly for both healthcare professionals and patients,” Lumme added.

For extrusion-related components, MDMs are focused on dose accuracy and material inertness when exposed to the active ingredients. “Stringent adherence to tight tolerances and concentricity in tubing manufacturing is required to ensure precise dosing,” said Burnett. “Additionally, a diverse array of material options and extensive expertise is also essential for customizing solutions to meet the specific compatibility requirements of different drug classes.”

Ultimately, MDMs want drug delivery systems that offer precise control over dosage and administration, ensuring accurate delivery of medications to targeted areas within the body. They also seek drug delivery platforms that can be tailored to specific therapeutic applications and patient needs, allowing for customization of dosing regimens and delivery mechanisms. “It is even better if these drug delivery systems seamlessly integrate with existing medical devices and technologies, enabling compatibility with healthcare infrastructure and workflows,” said O’Keeffe. “Scalability and efficient manufacturing processes are also critical for MDMs that require drug delivery products that can be produced cost-effectively at scale to meet market demand while maintaining the highest standards of quality.”

Manufacturing Methods and Technologies

The science behind drug delivery has advanced rapidly in recent years. New drug device systems are much more functional and effective when compared to legacy systems. New systems utilize nanomaterials and/or miniaturized devices with multifunctional components “that are biocompatible, biodegradable, and have high viscoelasticity with an extended circulating half-life,” said Ezike et al. “Microelectromechanical systems [MEMS] have vast applications for drug delivery. Devices produced with MEMS incorporate microfabrication techniques to produce micro/nano-sized electromechanical and mechanical devices or implants.”²

For example, the reservoir is a key part of a drug delivery device. Most single-reservoir systems have a relatively large port that can contain a single drug. “It is thus able to contain a relatively larger amount of drug and is also suited for long-term usage as it can be refilled,” said Ezike et al. “On the other hand, multi-reservoirs that comprise different ports [within the same substrate] that separately store drugs can be incorporated into these devices.”²

To maximize the efficient use of high-cost drugs, “there is also a growing need to enhance drug release efficiency to minimize waste and maximize therapeutic efficacy,” said Lumme. “This includes incorporating high-efficiency media in reservoir systems in devices such as nebulizers or topical applicators, which allow for precise drug delivery with minimal residual drug left in the device, ultimately reducing costs and optimizing patient outcomes.”

On the device side of combination products, as drug delivery devices and pharmaceutical manufacturing processes become more complex, pharmaceutical-grade, high-performance polyetheretherketone (PEEK) is a popular material among design engineers. PEEK can be micro-molded at shot sizes below 0.1 g to create miniature functional parts with wall thicknesses of 50 µm. It can be used to make microneedles for drug delivery with a tip radius of 30 µm. “The strength and stiffness of PEEK are being used in devices where the forces required would typically require the properties of metals,” explained Marcus Jarman-Smith and Yann Treguier of Victrex in an ONdrugDelivery article. “For example, on-body delivery systems and large-volume injection have seen increases in volume (e.g., from 1.5 mL to 3 mL) or a more-viscous rheology of the formulation (>50 cP), which can require pressures of 600 psi for 2.5 mL volumes. In respiratory devices, PEEK has been selected for inhalers using mechanical power to generate an aerosol, such as soft mist inhalers.”³

“In other industry sectors,” noted the authors, “PEEK has decades of use-case experience in highly demanding applications that could translate well to the pharmaceutical and drug delivery device sectors.”

Another production improvement is the marked increase in high-volume automation in manufacturing processes. In cases where materials are too fragile for automated assembly, such as membranes, “we can replace them with innovative 3D filtration media that fit the device precisely and will not break in assembly,” said Lumme. “Within these high-volume automated assembly processes, visually inspected parts can still cause problems if there are variations that are not obvious to the naked eye. Innovations in quality inspection equipment have enabled component manufacturers to perform 100% inspection across a custom defined set of specifications, ensuring that every component meets stringent quality standards.”

O’Keeffe concurred that quality inspection is crucial for ensuring the quality, safety, and efficacy of drug delivery products. Various techniques, including optical inspection, dimensional measurement, and functional testing, can be employed to verify product quality and compliance with regulatory standards.

“Automated inspection systems help detect defects and deviations from specifications, ensuring that only high-quality products reach the market,” added O’Keeffe. “Additionally, advancements in artificial intelligence and machine learning are being utilized to enhance the efficiency and accuracy of quality inspection processes in the pharmaceutical and medical device industries.”

Proprietary systems and methods developed in-house by CDMOs for specific needs often win them the job with an MDM.

For example, MDMs often ask their CDMOs to demonstrate the feasibility of delivering a novel active pharmaceutical ingredient (API), where the MDM may have only a single gram of the high-cost material to work with. “We have developed some clever approaches that allow us to manufacture drug-eluting micro implants using as little as 100 mg of API and make sufficient samples for preclinical studies,” said Arps. “For size, we are making drug-eluting implants less than 100 microns in diameter that can weigh less than 100 micrograms; in some cases, we’re controlling critical dimensions of implants to as little as five microns.”

Advances in additive manufacturing (AM) enable the rapid prototyping of custom geometries and components, allowing for faster iteration and testing of designs. AM is often a helpful tool in prototyping combination products such as new injectors. A big challenge is the limited availability of biocompatible materials suitable for AM processes. Although there are materials approved for medical use, such as certain biocompatible polymers and metals, not all materials are suitable for drug delivery applications due to concerns about compatibility, degradation, surface quality, and leaching of substances into the drug product.

“AM processes can result in surfaces that are rough or porous, which may impact the performance of drug delivery devices,” said O’Keeffe. “Surface roughness can affect drug release kinetics, while porosity may lead to issues such as drug degradation or microbial contamination.”

Despite these challenges, AM continues to be an area of active research and development in the field of drug delivery. “Advances in materials science, process optimization, and quality assurance techniques are helping to address some of these challenges and expand the capabilities of AM for producing drug delivery/combination products,” said O’Keeffe.

Moving Forward

Technology, materials, and designs continue to evolve rapidly for drug delivery/combination products, with a focus on ease of use and reliability. For example, long-acting injectables (LAIs) provide patients with a better compliance solution for chronic diseases. LAIs are typically formulated in a delivery matrix that provides extended release over a specific period. Steady progress is being made on developing needle-free vaccines—for example, Vaxxas is testing a novel vaccine delivery system that uses a patch covered with an ultra-high-density array of vaccine-coated microprojections—invisible to the human eye—that, when activated by a trigger, efficiently delivers the vaccine dose to the immune cells immediately below the skin surface.⁴ Advancements are also being made in gene therapy delivery systems, including viral vectors and lipid nanoparticles. These systems enable targeted delivery of genetic material to specific cells or tissues, opening up new possibilities for treating genetic disorders, cancer, and other diseases at the molecular level.

Nanofabrication technologies will continue to advance and develop a wider range of nanoformulations for drug delivery, including solid lipid nanoparticles, polymeric nanoparticles, nanostructured lipid carriers, and microemulsions. “Nanofabrication techniques will also be adopted to improve a compound’s loading, encapsulation, yield, and stability compared to other methods,” stated Pingale et al. “We anticipate many more nanofabrication techniques will emerge for developing novel drug delivery systems.”⁵

The constant challenge in drug delivery is getting the release of a customer’s drug “just right”—not too fast and not too slow. For a bioresorbable implant, it is critical to have the right polymer or polymer blend so it fully resorbs as quickly as possible after releasing the drug. Increasingly, there is an unmet need for enabling patient-centric autoinjector solutions that meet the challenging requirements of today’s novel bio-therapies. The complexity of the formulations and delivery needs of biologics have brought to light some of the limitations of existing device technologies to handle higher concentrations, doses, and viscosities. SMC’s Bios platform provides an enabling solution to deliver large volumes (up to 5 ml) and high viscosities (of 1,000+ cP). Bios provides a platform solution for a wide operational window using ISO standard staked-needle syringes (glass and plastic) and an ergonomic design for patient benefits.

O’Keeffe points out that many MDMs underestimate how advanced technologies and novel approaches can be integrated into drug delivery/combination products to address unmet medical needs. Examples of capabilities that MDMs may not fully consider are:

• Targeted drug delivery—MDMs often underestimate the potential for targeted drug delivery systems to precisely deliver medications to specific tissues or cells within the body. “Advances in nanotechnology, biomaterials, and microfluidics have enabled the development of sophisticated drug delivery devices capable of targeting diseased tissues while minimizing systemic side effects,” said O’Keeffe.
• Personalized medicine—Treatments can be tailored to individual patient needs based on their genetic makeup, physiology, and lifestyle factors. Advancements in genomics, biomarkers, and data analytics have made personalized drug delivery solutions increasingly feasible, allowing for optimized dosing regimens and improved patient outcomes.
• Implantable devices for chronic conditions—Implantable drug delivery devices have the potential to manage chronic conditions such as diabetes, cardiovascular disease, and chronic pain. These devices can sustain the release of medications over extended periods, reducing the need for frequent dosing and improving patient compliance and quality of life.
• Remote monitoring and control—MDMs may not fully appreciate the capabilities of remote monitoring and control technologies in drug delivery devices. These technologies enable real-time monitoring of patient adherence and treatment response, allowing for timely adjustments to dosing regimens and improved clinical outcomes.

Expanding on these possibilities in drug delivery/combination products requires education, collaboration, and exposure to cutting-edge research and development in the field. “By fostering dialogue and partnerships between OEMs, academic researchers, healthcare providers, contract manufacturers, and regulatory agencies, the industry can work together to unlock the full potential of drug delivery technologies and improve patient care,” said O’Keeffe.

To speed up the discovery and development of life-saving/life-extending therapies, MDMs that have deep expertise in medical component design and engineering often collaborate with pharma manufacturers to expedite the customization process to swiftly launch tailored products. “With customization,” said Lumme, “manufacturers can unlock new possibilities and drive innovation in their drug delivery products to further differentiate them in the market.”

“Custom is the new normal,” said Khanolkar. “There is need for more customizable solutions for the patients. Platform solutions help address the need of a flexible design solution to cover requirements from different patient groups and dosage regimens.” 

References

1. tinyurl.com/mpo240621
2. tinyurl.com/mpo240622
3. tinyurl.com/mpo240623
4. tinyurl.com/mpo240624
5. tinyurl.com/mpo240625

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Mark Crawford is a full-time freelance business and marketing/communications writer based in Corrales, N.M. His clients range from startups to global manufacturing leaders. He has written for MPO and ODT magazines for more than 15 years and is the author of five books.