In this first blog of our four-part series, Dr Erika Kovacs, Senior Director of Bioassay, details how phase-appropriate bioassays and functional assessments deliver decision-ready, regulatory-aligned data from discovery through commercial manufacturing.
Streamlining Drug Development Through Strategic, Stage-Specific Bioassays and Functional Assessments
Bioassays and functional assessments are indispensable tools in the drug development process, offering critical insights into therapeutic candidates’ potency, safety, and mechanisms of action. By precisely measuring biological activity using a range of methods, from simple biochemical assays through to complex spheroid and co-culture assays, these tests guide pivotal decisions across early discovery, lead optimization, preclinical (pre-IND) evaluation, and clinical trials, as well as into commercial manufacturing. However, their true value is unlocked when the right assay is employed at the right stage of development. This strategic timing not only streamlines the development process by preventing costly setbacks but also ensures the safety and efficacy profiles of the new drug fit expectations to drive therapeutic success.
Importance of Functional Assessments
Bioassays are analytical methods used to determine the biological activity or potency of therapeutic compounds by measuring their effects on living cells, tissues, or organisms. Functional assessments evaluate how a candidate interacts with biological targets to confirm mechanism of action (MoA) and therapeutic potential. From initial high-throughput screening, which rapidly identify promising candidates, to detailed preclinical characterization and ultimately potency assessment for lot release to support commercial manufacturing, these assays critically inform decisions at every stage.
By incorporating a phase-appropriate approach that increases the level of rigor and relevance at each milestone, starting from initial proof of concept studies through to clinical trials and commercial lot-release, developers can align assay complexity with regulatory demands. Furthermore, when used as part of Abzena’s broader approach to developability (which assesses candidate molecules for manufacturability & immunogenicity as well as functional performance), we aim to enhance the likelihood of clinical success by ensuring that only the best-characterized and most promising candidates advance through the drug development pipeline.
Selecting the Right Assay
Choosing the right assay at the right development stage is critical to the success and efficiency of drug development. Early in discovery, high-throughput screening assays are essential to quickly and efficiently identify candidates with desired biological activities while eliminating those with undesirable properties. Material availability is often limited so at this stage, speed, sensitivity, and reproducibility using simple assays are prioritized to effectively narrow down the pool of candidates.
As development advances into lead characterization and IND-enabling studies, assays must become increasingly sophisticated, reflecting the candidate’s precise MoA and with a focus on bridging the translational gap between the early studies and clinical efficacy. Here, Abzena uses advanced methodologies such as primary cell-based assays, kinetic assays, co-cultures, and 3D cellular models to provide biologically relevant and predictive insights. These assays enhance confidence in candidate performance, informing critical go/no-go decisions and preparing candidates for preclinical evaluation.
In preclinical development, clinical trials, and lot release, assays must meet stringent regulatory standards, demanding accuracy, precision, sensitivity, robustness, and reproducibility. There’s a critical trade-off between assay complexity and suitability as a lot release assay. Abzena expertly manages this balance, strategically selecting assays that provide the right level of biological relevance without compromising efficiency, ultimately ensuring candidates progress smoothly toward commercialization.
Tailoring Assay Selection to Modality and Mode of Action
Selecting the right bioassay strategy requires careful consideration of therapeutic modalities and mechanisms of action (MoAs). Given that each therapeutic class has unique biological attributes, it is critical to choose assays aligned explicitly with the modality and development stage to ensure that the chosen assays are fit for purpose and enable selecting the best candidate to progress into the clinic.
Antibody-Drug Conjugates (ADCs)
ADCs involve complex, multi-step MoAs, including targeted payload delivery, internalization, payload release, and often bystander effects. Initial screening assays typically assess internalization efficiency and basic endpoint viability. During lead characterization, assays become more advanced, including detailed evaluations of trafficking, real-time cytotoxicity monitoring, sophisticated 3D cytotoxicity models, and specialized bystander assays designed to replicate the complexities of tumor microenvironments. Lot release assays utilize robust yet simple endpoint viability assessments that align with regulatory standards.
Antibody Oligonucleotide Conjugates (AOCs)
AOCs occasionally function through gene or protein knockdown mechanisms. At the proof-of-concept stage, assays validate the effectiveness of target knockdown. Candidate screening typically involves internalization and initial knockdown efficiency assays to identify viable candidates swiftly. For lead selection and characterization, assays progress to assess trafficking, endosomal escape, and broader downstream functional impacts of the knockdown. For commercial applications, specific target-dependent assays ensure precise, reproducible potency measures to satisfy regulatory criteria.
Bispecific Immunomodulators (e.g., T-cell engagers)
Bispecific immunomodulators demand assays that evaluate dual-target interactions and immune activation. Proof-of-concept studies typically employ primary T-cell activation assays and cytotoxicity evaluations to validate therapeutic potential. Screening and optimization phases utilize binding assessments using e.g. Biacore, alongside T-cell activation reporter assays and stability studies. During lead characterization, a cell killing assay using primary T-cells can again be utilized, and cytokine release assays ensure comprehensive safety profiling. Lot release assays revert to robust and reproducible T-cell activation reporter assays to consistently meet stringent regulatory requirements.
Biologics with Fc-mediated Mechanisms of Action (e.g., via ADCC or complement activation.
Fc-mediated biologics require careful examination of effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Initial candidate screening typically uses high-throughput ADCC reporter assays, or binding to Fc gamma receptors using Biacore. Subsequent lead characterization stages escalate in complexity, using assays based on peripheral blood mononuclear cells (PBMCs) as effectors, and assessing mechanisms such as complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). At the lot release stage, simplified yet precise reporter assays offer the consistency and regulatory compliance required.
Through tailored assay selection that matches modality-specific and phase-appropriate needs, Abzena delivers streamlined progression, robust data, and regulatory compliance, ultimately enhancing the likelihood of clinical success and effective commercialization.
Relative Potency Assay Development
Abzena has recently launched a phase-appropriate GMP relative potency assay service which demonstrates our focus on delivering scientifically robust and regulatorily aligned solutions throughout the drug development process. Relative potency assays measure a drug candidate’s biological activity compared to a reference standard, serving as a critical indicator of product quality and consistency.
Abzena streamlines the development of these assays by integrating MoA-reflective methods tailored to each phase of drug development. For instance, in early development to support cell line development (CLD) and formulation activities, a more high-throughput relative potency assay might focus on evaluating key binding activities, while later-phase assays demand true functional cell-based assays with higher accuracy and tighter acceptance criteria to comply with regulatory guidelines. This staged approach ensures assays are fit-for-purpose at each phase of drug development, delivering fully regulatory-compliant data efficiently.
Collaboration and Expertise: The Abzena Advantage
Successful drug development requires more than scientific innovation, it demands strategic partnerships built on expertise and collaboration. At Abzena, we leverage extensive global experience in complex biologics, bioconjugates, antibody-drug conjugates (ADCs), antibody-oligo candidates (AOCs) and novel therapeutic modalities like bi/multi-specifics. With state-of-the-art facilities across the US and UK, our multidisciplinary teams ensure seamless progression from discovery through commercialization.
Our team advises on phase-appropriate bioassay selection strategies to maintain a smooth transition through every development milestone, ensuring compliance with evolving regulatory requirements. By working closely with customers, we bring deep scientific knowledge, innovative assay strategies, and proven regulatory expertise to each project, positioning therapeutic candidates for success.
Selecting the right assay at the right time is crucial for streamlining development, demonstrating phase-appropriate rigor, enhancing safety, and maximizing therapeutic potential. We invite you to explore Abzena’s comprehensive assay services, including our newly launched, GMP relative potency assays, to accelerate your program, reduce risk, and confidently advance your therapies toward approval.
