The landscape of biologics, including monoclonal antibodies (mAbs), recombinant proteins, and nucleic acid therapies, has significantly impacted disease treatment across various medical fields. However, the predominant reliance on parenteral administration, such as intravenous and subcutaneous injections, presents challenges related to patient compliance, safety, and accessibility. Consequently, there is a pressing need for non-parenteral alternatives, including oral, inhaled, transdermal, and intranasal delivery systems.
The exploration of these alternative delivery methods addresses the limitations posed by parenteral routes. Current research highlights the molecular and technical barriers to delivering biologics non-invasively, while also showcasing advancements in formulation technologies and collaborative efforts within the biopharmaceutical sector. Recent developments by contract manufacturers, biotechnology firms, and academic institutions signal progress in creating delivery systems that prioritize patient-centric approaches.
Evolution of Biologics Delivery
Despite the advancements in biologics such as mAbs and recombinant proteins, over 95% of these therapies are still administered via injections. This heavy reliance on injections is largely due to the complex physicochemical characteristics of biologics, which include large molecular sizes and structural fragility, making simple oral dosing unfeasible. The necessity for repeated injections can lead to decreased patient adherence, needle phobia, and increased strain on healthcare systems.
As a result, the industry is increasingly focusing on less invasive delivery options. Oral and inhaled biologics are garnering significant research and development investment due to their potential for improved patient acceptance, ease of home administration, and alignment with personalized medicine objectives. Market analyses indicate robust growth prospects for oral biologics, projected to expand at a fast pace, while inhalation contract development and manufacturing organizations are also expected to experience notable growth.
Challenges in Non-Parenteral Delivery
Biologics are inherently more complex than small-molecule drugs, presenting unique challenges due to their large molecular weights and sensitivity to environmental factors such as pH and temperature. The high cost of biologics manufacturing further emphasizes the need for efficient bioavailability, as even minimal losses during administration can render a product economically unfeasible.
Oral delivery faces specific obstacles, including rapid degradation in the gastrointestinal tract, barriers preventing the absorption of large molecules, and variability in patient responses. Successful clinical applications of oral biologics remain limited, although some products have shown potential. Inhalation delivery offers direct access to circulation, but has been hampered by past commercialization challenges, notably with inhaled insulins, which highlighted issues with device usability and cost.
Innovative Formulation Technologies
Recent advancements in particle engineering and inhalation platforms are paving the way for improved biologics delivery. For instance, companies like Lonza are enhancing pharmacokinetics and bioavailability through innovative spray-drying techniques and collaborations, such as those with Ethris to stabilize mRNA vaccines. Furthermore, CrystecPharma is utilizing modified supercritical anti-solvent technology to create stable dry particles for inhaled therapies.
In addition to inhalation methods, advancements in oral delivery systems are also underway. Lonza is developing smart capsules that target specific gastrointestinal sites, while Catalent Pharma Solutions is investigating lipid-based formulations to enhance the absorption of macromolecules. Other initiatives, such as US Specialty Formulations” QYNDR, a drinkable vaccine, seek to bypass the degradation barriers in the gastrointestinal tract by activating mucosal immunity directly.
Emerging delivery methods, including transdermal microneedle patches and jet injectors, are also being explored for smaller biologics, such as peptide vaccines, which could improve delivery in certain populations, particularly in resource-limited settings.
Market Dynamics and Future Perspectives
The COVID-19 pandemic has accelerated the development of non-parenteral biologics, particularly in inhaled and intranasal formats. The future holds promise for self-administered therapies that may offer localized treatment options while providing systemic benefits. Despite the progress, challenges remain in achieving effective oral or inhaled mAbs, with significant work needed to address issues of molecular integrity, absorption profiles, and long-term safety data.
The diverse range of biologics under development suggests that a variety of non-parenteral strategies will coexist, tailored to specific therapeutic needs. The overarching goal remains to enhance patient-centric care, providing convenient, non-invasive, and accessible treatment options that alleviate healthcare burdens and improve adherence to therapies.
