A stage-by-stage guide to potency strategy in biologics development

Potency testing is a cornerstone of biologics development, serving as a critical quality attribute that links a product’s mechanism of action to its intended therapeutic effect. It provides a quantitative measure of a drug’s biological activity and ensures that it performs its intended function consistently and safely. In this article, we will explore the role potency testing plays in each stage of a biological treatment's development and lifecycle. 

Potency evidence forms is a key part of the evidence that regulatory bodies require when evaluating market authorization, as indicated by the international specifications for biotechnological and biological products (ICH Q6B).

But its role goes far beyond simply being a regulatory requirement. Through potency assays, developers generate the biologically relevant data needed to inform strategic decisions across the product lifecycle – from candidate selection and process development to manufacturing and quality control and subsequent commercialization. 

As biologics and advanced therapeutic modalities grow increasingly sophisticated and complex, potency testing strategies and technologies must evolve in parallel. Assays must be scientifically relevant, fit for purpose, and capable of supporting both product development and regulatory requirements throughout the product lifecycle.

To meet these demands, developers are increasingly turning to function-reflective approaches, such as cell-based assays, that measure biological activity in biological relevant systems. These advanced methods provide a more comprehensive understanding of therapeutic function and offer deeper insights into a product’s clinical potential.

Why is potency testing different in biologics?

Biologic therapies are revolutionizing medicine and helping to develop innovative treatment that address unmet medical needs. Biologics are medicines derived from living organisms or produced using biotechnology that target specific molecular pathways to elicit a desired therapeutic effect. Biologics are designed to act on particular biological structures and functions (molecules, cells, or receptors) involved in disease processes. This makes them particularly valuable treatment options for autoimmune diseases, inflammatory disorders, cancers, genetic disorders and more. Major types of biologic therapies include engineered antibodies, recombinant proteins, vaccines, and advanced therapies including cell and gene therapies.

As biologics and advanced therapeutic modalities grow increasingly sophisticated and complex, potency testing strategies and technologies must evolve in parallel. Assays must be scientifically relevant, fit for purpose, and capable of supporting both product development and regulatory requirements throughout the product lifecycle.

To meet these demands, developers are increasingly turning to function-reflective approaches, such as cell-based assays, that measure biological activity in biological relevant systems. These advanced methods provide a more comprehensive understanding of therapeutic function and offer deeper insights into a product’s clinical potential.

How to develop a successful potency strategy 

A successful potency strategy for biologics starts with selecting the right assay approach as early as possible in development. Early assay design helps build a deep understanding of the therapeutic candidate’s mechanism of action (MoA), establish reproducibility, and generate the data needed to guide product and process decisions.

Choosing robust and scalable assays that can be qualified, validated and transfered later creates a consistent framework for monitoring biological activity throughout development and manufacturing. Ultimately, defining the potency testing early in the discovery and development process helps lay the foundation for efficient development, long-term quality control, and a smoother path to regulatory approval.

By understanding the role potency testing plays throughout and beyond drug development, you can better identify and design the right strategy for your development program, ensuring that the evidence built can stand the test of product development, regulatory scrutiny, and lifecycle management.

Pre-clinical research

During pre-clinical studies it is crucial to balance speed with long-term scalability by employing a potency strategy that can support rapid decision-making today while remaining suitable for later-stage development and commercialization. At this point, potency assays are primarily used to demonstrate proof of concept by confirming that a therapeutic candidate exhibits the intended biological activity.

As the program evolves and testing strategies crystallize, potency testing builds on the evidence generated during discovery, providing deeper insights into product biology and supporting characterization and safety and efficacy assessments. The resulting data helps strengthen understanding of the candidate while informing key development decisions.

Potency assessment also begins to play an increasingly important role in establishing the analytical foundation for Chemistry, Manufacturing and Controls (CMC). By generating reliable measures of biological activity, potency assays help support the transition from exploratory research to the development of a scalable, controlled, and regulatory-compliant product.

To ensure continuity throughout development, potency assays should be selected with future qualification, validation, and technology transfer requirements in mind. Choosing robust, scalable, and transferable methods early can facilitate smoother progression through subsequent phases, support interactions with external partners and quality-control laboratories, and reduce the risk of delays associated with assay changes later in development.

Clinical development

Clinical development represents the critical test in a therapeutic product’s development, as it is at this stage that safety and efficacy are evaluated in human subjects. Understandably, as the programs advance into the clinics, regulatory requirements for potency assays become much more defined and stringent, reflecting the growing importance of  consistent product performance and quality.

At this stage, potency assays play a central role in generating the evidence needed to support market authorization. In addition to confirming therapeutic activity, they help demonstrate product safety, efficacy, stability, and consistency throughout development. Potency testing also becomes essential for establishing comparability between batches and ensuring a product is suitable for lot release and large-scale manufacturing.

As assays transition from development tools to regulatory-critical methods, validation requirements become more rigorous. While phase-appropriate validation requirements during discovery and early development are more permissive, clinical development requires fully validated and well-characterized assays. Ultimately, validated potency assays provide evidence that a product's biological activity remains consistent over time and that its mechanism of action, stability, and quality meets the standards required for commercialization.

Regulatory filing

Regulatory submission is the moment of truth and the culmination of years of development, where the generated body of evidence is put under the severe scrutiny of regulatory bodies.
Potency data become a central component of the regulatory package, forming a comprehensive picture of the therapeutic product performance and clinical relevance rooted in a clear link between the therapeutic MoA and the observed clinical benefits.

Potency testing plays a critical role in building confidence that the product consistently delivers the biological function underlying its intended clinical benefit. These data support key elements of the Chemistry, Manufacturing and Controls (CMC) section, helping justify product specifications, release criteria, and manufacturing controls. Potency evidence is also used to demonstrate comparability across changes in manufacturing, formulation, process or site, while confirming that all batches consistently meet predefined quality standards and deliver comparable biological activity.

In addition, potency assays support lot release and stability programs by providing validated methods to monitor a product’s performance throughout its shelf life. Together, these data demonstrate that the commercial product remains consistent with the one evaluated during development and clinical testing.

Because potency testing sits at the intersection of product quality, manufacturing consistency, and clinical relevance, it is often a focal point of regulatory review. Insufficient or poorly justified potency data can lead to regulatory questions, approval delays, or even failure to obtain marketing authorization. Conversely, a robust potency data package strengthens confidence in the product's safety, efficacy, and quality, making it a cornerstone of successful regulatory approval and lifecycle management.

Post approval

Potency remains essential long after a product receives marketing authorization. Once the product is commercially available, the focus of potency testing shifts from proving that a therapy works to ensuring that every batch continues to perform as intended throughout a product’s entire commercial lifecycle.

As production scales up, potency helps ensure that the product remains comparable regardless of changes in process, equipment, scale, formulation, raw materials or manufacturing site.

Manufacturers also use potency measures to ensure that each lot meets predefined acceptance criteria and that manufacturing processes continue to produce products with the same biological activity observed during development and clinical testing.

Potency therefore becomes a necessary tool for monitoring the product’s stability, and to demonstrate the that the safety, efficacy, and quality profile established during clinical development is retained throughout the product’s shelf life.

Beyond routine quality control, potency testing plays a central role in lifecycle management. It provides the analytical foundation needed to support manufacturing optimization, process improvements, post-approval changes, and production expansion, enabling companies to maintain consistent product quality while meeting evolving commercial and regulatory requirements.

How Svar supports you

At Svar Life Science, we support biopharma companies by translating complex biology into robust, regulatory-ready assay solutions that help you navigate the evolving complexities of modern biologic therapeutics.

We know that the path of innovative life-changing treatments starts in the lab, years before they reach the patients, with future-proofed testing strategies and robust evidence that build confidence throughout the development continuum.

Robust and scalable potency assays help you create a consistent framework for generating the data needed to guide product and process decisions and lay the foundation for efficient development, long-term quality control and a smoother path to regulatory approval.