Understanding the evolving trends in the complex biologics landscape
Complex biologics such as antibody-drug conjugates (ADCs), innovative vaccines, and gene and cell therapies (GCTs) are increasingly entering the development pipeline, demanding a comprehensive understanding of various scientific disciplines for their production. Harnessing the power of these revolutionary products will require an in-depth understanding of the interplay between biology and chemistry to advance drug design, development and manufacturing.
Tom Wilson, Contract Manufacturing Lead at Pfizer CentreOne shares his unique insights into what’s driving biotechs working with the next era of complex biologics to rely on expert contract development and manufacturing organizations (CDMOs).
Navigating the emergence of increasingly complex biologics
The rapid expansion of the pharmaceutical industry is largely attributed to the introduction of innovative biologic modalities like vaccines, antibody-drug conjugates (ADCs), and gene cell therapies (GCTs). These new modalities go beyond traditional monoclonal antibody therapies and small-molecule drugs, offering enhanced specificity, reduced off-target interactions, and longer-lasting therapeutic effects.
However, despite their immense potential, these products are inherently complex. Their development and manufacturing require expertise in various scientific disciplines, including organic, medicinal, and analytical chemistry, as well as molecular and cellular biology, pharmacology, and immunology. This complexity presents challenges that require close collaboration among specialists to ensure the successful navigation of the relatively new therapeutic compounds.
Addressing challenges in ADC production
Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of cytotoxic drugs, offering targeted treatment for cancer. These therapies have shown greater efficacy than conventional chemotherapies due to their unique combination of biological and chemical components. As a result, the U.S. FDA has approved 13 ADCs for treating various hematological and solid organ cancers, demonstrating their potential in cancer therapy [4].
As ADCs continue to advance, developers and manufacturers face various challenges during production. One significant aspect is the increasing complexity of conjugation reactions. These reactions often involve multiple steps and may necessitate purification processes between each stage, contributing to the intricacies of ADC development and manufacturing.
Effective cytotoxin manufacturing also necessitates biological and chemical expertise, including conjugation support and controlled substance handling. Close collaboration among project teams, with a comprehensive understanding of project components, is crucial for seamlessly integrating biological and chemical elements.
Promoting the future of GCTs
The GCT space is undergoing rapid expansion, revolutionizing the field of medicine by offering tailored treatments for patients with genetic diseases. With over 2,100 gene therapies in the development pipeline, GCTs are poised to address a wide range of indications, from cancers to rare diseases and neurological disorders. The ability to personalize GCTs to the individual patient’s genetic makeup, disease characteristics, and response to therapy is transforming the healthcare paradigm.
However, the complexity of manufacturing these therapies presents significant challenges. The precise execution of the intricate steps involved in cell culture, fermentation, purification, and quality control is crucial for guaranteeing the safety, efficacy, and consistency of the final product. GCTs also have distinct requirements throughout the manufacturing process, including the need to separate full viral vector capsids. Scaling up these products introduces additional challenges, particularly in triple transfection steps. A solid grasp of fluid dynamics is essential to enhance the probability of an effective and successful transfection process during scale-up.
Revolutionizing drug delivery
For successful therapeutic outcomes, efficient drug delivery is essential, particularly for introducing new vaccines that often rely on fragile biologic drug substances that are prone to degradation by bodily enzymes.
Advancements in chemistry and biologics have produced innovative drug delivery systems (DDSs) like lipid nanoparticles that improve bioavailability, prolong drug release, and enhance therapeutic outcomes. Consequently, biotech companies increasingly rely on DDS platforms to enhance their biologics’ selectivity, effectiveness, and safety. Common DDSs for biologics include liposomes, microspheres, albumin nanoparticles, and micelles, besides LNPs.
However, utilizing the potential of these delivery systems requires extensive expertise since DDS platforms add complexity to drug development and manufacturing. This complexity necessitates segregation strategies, specialized processing equipment, and advanced analytical technologies. More advanced analytical techniques are often required for therapies using DDSs to evaluate the drug product’s physicochemical properties and define the advantages provided by the delivery system. These techniques can evaluate the carrier’s impact on the drug product’s extended release, bioavailability, potency, and target specificity.
Partnerships propelling future complex biologic success
With ongoing advancements in the biologics space, we can expect a continuous stream of innovative therapies that offer improved outcomes for patients across a range of diseases and a future of medicine promises that are more precise, effective, and patient-centric than ever before.
But for biotechs to unlock the potential of their complex biologics in the future, they must overcome the challenges that stem from their complexity. By relying on contract development and manufacturing organizations (CDMOs) at the forefront of innovation that offer the expertise, capabilities, and facilities needed to effectively deliver the project to market, these developers can simplify their product’s journey to market and to patients. This includes leveraging decades of experience supporting a broad range of complex therapeutics, including ADCs, vaccines, and GCTs, as well as broad capabilities to support liquid formulation and lyophilization, pre-filled syringes, vials, and cartridges.
Discover more about how we can help you skillfully maneuver through the complexities of biologics development and manufacturing in our sterile injectable application note: