The advent and proliferation of targeted modalities represent an evolutionary leap forward in drug development. By binding specifically to receptors or biological targets, such therapies ensure a more direct and effective treatment while reducing systemic exposure and unintended side effects – a clear and marked improvement that distinguishes targeted modalities from conventional small molecule and biologic formulations. 

Two prominent targeted modalities, antibody-drug conjugates (ADCs) and targeted protein degraders (TPDs), are poised for profound near-future growth. The ADC market, for instance, is projected to triple in size in the course of just a decade, from $3.5 billion in 2020 to $13.1 billion by 2030 – a compound annual growth rate (CAGR) eclipsing 17%. Similarly, the global TPD landscape was valued at $541.98 million in 2024, and is expected to reach $3.55 billion by 2034 while achieving a CAGR of 20.7%. Part of this outsized growth can be attributed to application expansion; while targeted modalities are typically associated with oncology, their usefulness is showing promise for diseases where specific pathways can be leveraged for therapeutic intervention. 

Regardless of their application, the rapid rise of targeted modalities is the result of medical science breakthroughs, both large and small. For one, advancements in genetic research have deepened researchers’ understanding of how individual genetic makeup influences both disease susceptibility and optimal treatment response. By tailoring therapies to address specific genetic markers, drug developers are forging paths toward precision medicines that provide highly effective solutions for distinct patient populations.

Second, improvements in drug discovery methodologies have enhanced the pharma sector’s ability to design treatments that deliver active pharmaceutical ingredients (APIs) directly to their intended targets. Unlike traditional therapies that distribute broadly within the body, targeted modalities minimize unnecessary exposure, reducing toxicity while bolstering therapeutic efficacy. 

Encouraging progress in areas like molecular engineering and computational drug design also have helped yield highly specific therapies. For many, such strides have been lifesaving, with ADCs and other precision-based approaches drastically improving outcomes for patients with conditions previously deemed untreatable.

Despite their promise, though, targeted therapies present unique development and manufacturing challenges. This article explores several such obstacles and suggests strategies for overcoming them.

Target Practices: Overcoming Heightened Development Challenges

Unsurprisingly given the “guided missile” approach that targeted modalities represent, many compounds utilized in such therapies are highly potent. Frequently, many also are especially sensitive to environmental factors like heat, light and oxygen, and necessitate specialized solubility and/or stability enhancement technologies to ensure efficacy over extended periods. For those reasons, lyophilization is commonly employed to safeguard the shelf life and stability of targeted modality therapies delivered via parenteral administration.

The high potency of most targeted modality compounds also demands stringent containment protocols during manufacturing. In addition to protecting operators from exposure, such measures are necessary to maintain drug product integrity, particularly for parenteral formulations administered intravenously, intramuscularly or subcutaneously. 

Targeted modalities also rely upon advanced and highly sensitive analytical techniques. Given their concentrations – often at the nanogram level or lower – highly sensitive assays are necessary to accurately detect and quantify the active compounds utilized in targeted modalities. Exceptionally keen analytical techniques must be developed to ensure quality and efficacy. For example, with complex molecules like ADCs, analytical methods must assess not only the presence of the therapeutic agent but also its biological activity. This underscores the necessity of rigorous bioassays and functional testing, above and beyond standard chemical characterization.

Increasingly, regulatory agencies are placing emphasis on incorporating quality elements from a product’s conception and initial development, rather than relying on post-development testing. Analytical methods serve as the foundation for maintaining quality throughout the drug development process, ensuring formulations remain stable and biologically active from manufacturing to patient administration. With targeted therapies, this from-inception approach to quality control becomes even more crucial given the formulation’s overall complexity. 

Scalability presents another high hurdle. Supporting targeted therapies through preclinical and early clinical trials, then translating these processes to larger scale batches, is often exceedingly complex. Ensuring reproducibility and maintaining the same level of precision at larger scales requires meticulous planning and robust quality control guardrails.

Here, it’s also worth noting that, from a production perspective, “large” can be a rather nebulous term. Unlike traditional pharmaceuticals produced in long-run batches, even “large” batches of targeted modality therapies often require shorter-run – and therefore more flexible – manufacturing processes. Facilities must be equipped to handle variable batch sizes while maintaining the necessary environmental controls to preserve drug stability and potency. 

Moreover, the manufacturing process must be adaptable to different formulation needs. Some targeted therapies may begin as parenteral formulations due to stability concerns but eventually transition to oral dosage forms. Such potentially platform- and delivery-shifting manufacturing scenarios favour entities with robust production capabilities and capacity, such as prominent contract development and manufacturing organizations (CDMOs). 

Outsourcing’s Outsized Role

Considering the various challenges – containment needs, analytical demands, scalability concerns and more – CDMOs will undoubtedly play increasingly vital roles in bringing targeted therapies to market. Many pharmaceutical companies, particularly small biotech firms, lack the specialized facilities and expertise required to develop and manufacture these complex treatments. In such scenarios, CDMOs provide mission-critical support by offering experience with highly potent compounds, advanced analytical capabilities, and flexible manufacturing solutions.

To serve as ideal partners for targeted modality projects, CDMOs must prioritize three key components: facility adaptability, cutting-edge equipment and, especially as this niche matures, expertise in the interconnected disciplines necessary for targeted drug development and production. To meet these lofty expectations, CDMOs will need to maintain a network of specialized partners to best address any gaps in capability, ensuring a streamlined pathway from drug discovery to commercialization. 

Notably, solutions as specialized as targeted modalities are best approached with technological agnosticism – an unbiased approach in which the manufacturing solution truly fits the molecule, rather than trying to shoehorn the molecule into legacy technology and equipment. Typically, this level of nimbleness is reserved for robust CDMOs with diversified, end-to-end drug development and production capabilities and infrastructure. 

CDMOs must also balance their expertise in both small-molecule and biologic drug production. As targeted modalities could involve hybrid approaches – ADCs, which combine a biologic (antibody) with a cytotoxic small-molecule drug, are a prime example here –integrated skillsets become invaluable.

Looking ahead, the coming decade promises significant and likely accelerated advancements in targeted modalities. While oncology remains the primary focus, emerging applications in neurology, autoimmune disorders, and rare diseases are gaining traction. Personalized therapies – perhaps even ones tailored to individual patients – represent the ultimate goal, with artificial intelligence (AI) playing an instrumental role in optimizing drug design and development.

Indeed, AI-driven insights are already accelerating drug discovery by identifying optimal targets and refining molecular structures. While AI’s role in drug product development is still in early stages, as more data becomes available its influence will grow exponentially, expediting formulation development and honing manufacturing processes.

Additionally, the regulatory landscape is evolving to accommodate the rapid advancements in targeted modalities. With many of these therapies classified as breakthrough treatments, agencies like the FDA and EMA are working to establish streamlined approval pathways that balance speed with safety.

Conclusion

Targeted modalities bring immense potential to transform patient care, but their success depends on leveraging the right expertise, technologies and partnerships. As the field evolves, CDMOs will continue to play crucial roles in enabling pharmaceutical companies to develop and deliver life-changing therapies with greater speed and precision.

Targeted modalities are, at present, the tip of the pharmacological spear: the industry’s most advanced tools to date in the fight against difficult-to-treat, often life-threatening diseases. In pushing the boundaries of medical science, such therapies require those developing and manufacturing them to be smarter, faster and more adaptable than ever before.

Anshul Gupte Ph.D., RAC Drugs is Vice President, Pharmaceutical Development for PCI Pharma Services, a CDMO providing integrated development, manufacturing and packaging services. Anshul has over 17 years of experience in concept, pharmaceutical development, and commercialization of drug product. He has experience in working on broad range of dosage forms – solid orals, liquids, sterile, topicals and has contributed to several branded and generic regulatory submissions for US and worldwide markets.