Biopharmaceutical Potency Testing: How Contract Labs Ensure Efficacy and Quality

Why Potency Testing Matters

Biopharmaceuticals, such as monoclonal antibodies, vaccines, recombinant proteins, and cell and gene therapies, represent one of the fastest-growing areas of modern medicine. Unlike small-molecule drugs, which can be fully characterized using chemical and physical methods, biopharmaceuticals are large, complex molecules produced in living systems. Their therapeutic activity is determined not just by chemical composition but by functional biological activity.

Potency testing provides the evidence that a biopharmaceutical does what it is intended to do. A well-designed potency assay confirms that the product exerts its expected biological effect at the right strength, ensuring that every dose administered to patients is both safe and effective.

For contract laboratories, potency testing has become an increasingly high-demand service. Pharmaceutical and biotechnology companies often outsource this critical testing to specialized labs that can provide validated, regulatory-compliant assays. By offering these services, contract labs play a vital role in bridging scientific innovation with regulatory and clinical expectations.

What Is Potency Testing?

In simple terms, potency is the quantitative measure of a drug’s biological activity. For biologics, this usually means measuring how effectively a product binds to a receptor, activates a signaling pathway, kills a target cell, or neutralizes a virus.

Unlike identity or purity testing, which confirm what a product is, potency testing focuses on what the product does.

Key applications of potency testing include:

• Preclinical development: Demonstrating mechanism of action (MoA) and supporting proof-of-concept studies.
• Clinical trials: Ensuring consistency of drug lots used across trial phases.
• Lot release testing: Verifying that each manufactured batch meets potency specifications before release.
• Stability studies: Confirming that potency remains intact throughout the product’s shelf life.
• Comparability and biosimilar testing: Establishing that a product maintains potency after manufacturing changes or when comparing to a reference biologic.

Because potency directly correlates with therapeutic effect, regulators consider it a critical quality attribute (CQA), placing it at the center of biopharmaceutical quality control.

Regulatory Framework

Global regulators are clear: potency testing is not optional. It is a legal requirement for biologics and must be performed using scientifically valid assays.

• United States (FDA):
  Per 21 CFR 610.10, each biologic must have an appropriate in vivo and/or in vitro assay, often biologically based, to measure potency.
• ICH Q6B:
  This harmonized guideline sets specifications for biotechnological products, including potency assays. It emphasizes that potency tests should reflect the product’s mechanism of action.
• WHO Technical Reports:
  Provide specific potency requirements for vaccines and blood-derived products, often including minimum acceptable potency values.
• Pharmacopoeias (USP, EP, JP):
  USP <1033>, <1034>, and <1044> outline bioassay validation, assay selection, and statistical analysis requirements.

For contract labs, staying current with these evolving standards is critical. Regulatory authorities often scrutinize potency assays during product approval, facility inspections, and post-market surveillance. A robust, validated potency test can be the deciding factor between approval and delay.

Potency Assay Types

No single assay suits every biopharmaceutical. Assay selection depends on the product’s mechanism of action, clinical indication, and regulatory expectations.

1. Cell-Based Bioassays

• Overview: Measure the drug’s functional activity in live cells.
• Applications: Common for monoclonal antibodies, cytokines, growth factors.
• Examples:
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) assays for cancer immunotherapies.
  • Proliferation assays for erythropoietin.
• Advantages: Directly link potency to MoA, providing strong regulatory confidence.
• Challenges: Variability in cell systems, longer assay times, need for strict quality control.

2. Binding Assays (ELISA, Surface Plasmon Resonance, Flow Cytometry)

• Overview: Measure how strongly a biopharmaceutical binds to its target.
• Applications: Monoclonal antibodies, receptor-binding proteins, vaccines.
• Advantages: Highly specific, reproducible, and faster than cell-based assays.
• Limitations: Do not always reflect downstream biological activity, so often used in combination with functional assays.

3. Animal-Based Assays

• Overview: Historically used when in vitro systems were unavailable.
• Applications: Some vaccines (e.g., potency testing of diphtheria/tetanus antitoxins).
• Limitations: Ethical concerns, variability, and high costs. Increasingly replaced by alternative assays, but still required in certain cases.

4. Emerging and Advanced Assays

• Reporter Gene Assays: Use engineered cells with a measurable genetic signal, improving sensitivity and throughput.
• High-Content Imaging Assays: Capture detailed cellular responses using microscopy and image analysis.
• Omics-Based Functional Readouts: Transcriptomics or proteomics to measure global functional changes.

Contract labs increasingly adopt these advanced approaches to provide clients with predictive, regulatory-acceptable data.

Challenges in Potency Testing

Despite its importance, potency testing is often one of the most complex aspects of biologic development.

• Assay Variability: Biological systems introduce variability. Rigorous assay validation and reference standards are required.
• Complex Mechanisms of Action: Some biologics act through multiple pathways, necessitating multiple orthogonal assays.
• Reference Standards: Potency is always measured relative to a standard, which must be carefully sourced, qualified, and maintained.
• Long Development Timelines: Potency assays can take months or years to develop and validate, delaying clinical programs.
• Biosimilars and Comparability Studies: Demonstrating equivalent potency to a reference product is a cornerstone of biosimilar approval.

For contract labs, offering solutions to these challenges—such as assay development services, advanced statistical analysis, and access to diverse platforms—creates a competitive advantage.

Latest Trends in Potency Testing

The field is evolving rapidly. Several trends are shaping the way contract labs deliver potency testing:

1. Automation & Digitalization
   Robotics, high-throughput plate readers, and AI-based image analysis reduce assay variability and accelerate turnaround times.
2. Use of Physiologically Relevant Cell Models
   Labs are shifting from immortalized cell lines to primary cells, induced pluripotent stem cells (iPSCs), and organoids, which more closely replicate in vivo responses.
3. Multi-Attribute Methods (MAMs)
   Integration of functional potency with structural and physicochemical characterization, providing a more holistic quality assessment.
4. Advanced Therapies
   Cell and gene therapies pose new challenges—how do you measure the potency of a therapy designed to alter genetic function? Labs are adopting vector copy number, transduction efficiency, and gene expression readouts as potency endpoints.
5. Regulatory Push for Alternatives to Animal Testing
   The FDA and EMA actively encourage reduction of animal-based potency tests, driving innovation in in vitro and computational models.

Outsource Potency Testing to Contract Labs

For many drug developers, outsourcing potency testing is not just a convenience but a necessity. Contract labs offer:

• Specialized Infrastructure: Maintaining validated potency assays, bioassay suites, and GMP-compliant systems is resource-intensive.
• Regulatory Experience: Contract labs are familiar with FDA and EMA expectations, helping sponsors navigate inspections and filings.
• Scalability: Labs can support testing from early R&D through global lot release, adjusting capacity as programs scale.
• Independent Validation: A third-party potency test adds credibility, particularly for biosimilars or outsourced manufacturing.
• Faster Timelines: Many labs already have platform assays in place, accelerating method development.

For biopharma companies, partnering with a contract lab reduces risk, speeds regulatory submissions, and ensures global compliance.

For contract laboratories, it represents both a challenge and a major growth opportunity. The ability to design, validate, and execute robust potency assays positions labs as indispensable partners in the biopharmaceutical ecosystem. As biologics and advanced therapies continue to expand, demand for innovative, reliable, and compliant potency testing will only increase—making it one of the most strategically important services for contract testing labs today.

This content includes text that has been generated with the assistance of AI. Contract Laboratory encourages the use of new tools and technologies that enhance our editorial process. Our full editorial policy can be found here.