The Importance of Good Manufacturing Practice (GMP)
Good Manufacturing Practice (GMP) ligand binding and potency assays are essential for ensuring the quality, safety, and regulatory compliance of biopharmaceutical products. These assays not only verify product integrity but also support regulatory submissions, lot release, and long-term stability programs. Below, we address some frequently asked questions (FAQs) related to their development and validation.
Over the years we have developed and validated many GMP assays to support our sponsors’ manufactured pharmaceuticals with GMP lot release testing and GMP stability testing in accordance with FDA, EMA and ICH standards.
GMP release/stability testing is critical to ensure the quality and safety of the products, confirming that they meet their specifications before drugs are released to the market and that shelf life is guaranteed under various storage conditions.
Developing a reliable and robust ligand binding assay requires an understanding of the context of use framework. In addition, determining biological activity is more complex than measuring concentration only. Bioassays often require live cells or other biological components that can be inherently variable, making reproducibility one of the major challenges. When designing assays, parameters such as optimal reagent concentrations, incubation times, temperature, and pH should be carefully investigated.
Standard Operating Procedures
The drafting of a standard operating procedure (SOP) for the method is an essential part of the assay development in a GMP-compliant quality system including controlled SOPs, trained analysts, qualified equipment/software, data integrity, controlled reference standards, system suitability, QC review, OOS/OOT-deviation investigation/CAPA and change control. Electronic systems for SOP management and data capture are increasingly recommended to align with regulatory expectations for data integrity (ALCOA+ principles).
The SOP should provide detailed instructions on the preparation of reagents, assay protocol and handling of the samples. It is also important to add quality control checks at various stages to monitor and ensure assay performance.
Validation of the GMP assay is the final step before it can be used for its purpose, demonstrating that the assay is accurate, precise, specific, and reproducible. Additional parameters such as linearity, range, and limits of detection/quantification should also be considered, depending on the assay’s intended use.
In conclusion, designing a biochemical assay using GMP grade reagents requires careful planning, thorough assay development, and rigorous validation in compliance with GMP guidelines.
Frequently Asked Questions
Here are a few FAQs which are often addressed during the development and validation of GMP grade assays:
Which applications are commonly used for GMP assays?
Lot release testing
Stability and comparability testing
What types of potency assays are commonly used?
Cell-based functional assays
Ligand binding assays
Enzymatic activity assays
Reporter gene assays
How do I choose the right potency assay for my drug product?
Selection depends on the product’s mechanism of action (MoA), intended therapeutic effect, and relevant biological endpoints. For example, antibody-based drugs often require cell-based assays for determining Fc-effector MoA (e.g., ADCC/CDC) or neutralisation/blocking MoA. A binding assay may also be acceptable if binding alone drives the clinical effect.
When do I need to have a validated GMP assay ready?
The typical lifecycle of GMP assays involves feasibility/optimisation (non-GMP) phases that require assay qualification (non-GMP) to support early clinical use. Full validation is needed for pivotal, marketing, or commercial release.
What regulatory guidelines govern potency assays under GMP?
ICH Q2 (Validation of Analytical Procedures)
ICH Q6B (Specifications for Biotechnological Products)
FDA and EMA guidance documents (e.g. Eudralex vol. 4)
How should acceptance criteria be set?
Set specifications using clinical lot performance, process capability, stability trends and method uncertainty. Engage cross-functional teams to ensure acceptance criteria are scientifically justified and aligned with regulatory expectations.
What parameters are typically validated for GMP assays?
Specificity and selectivity
Accuracy and precision
Robustness
System suitability
What is the role of reference standards in potency assays?
Reference standards ensure assay consistency and allow for relative potency comparisons between lots. Potency is often reported as relative potency versus a reference standard, assessed via parallel dose–response behavior.
How are reference standards qualified?
Through rigorous characterisation, stability studies, and traceability to a primary standard, if available.
Why can GMP assay results vary?
Biological variability in cell-based assays
Operator differences
Instrument performance variability
Reagent lot variability
How can variability be minimised?
Use of standardised protocols and trained personnel
Stringent reagent qualification
Ongoing assay performance monitoring
How is assay robustness maintained over time?
Through periodic system suitability checks, trending analysis of control results, and continued proficiency testing.
What are common pitfalls in GMP assay development?
Relying on non-qualified reference standards
Insufficient robustness testing during development
Failing to account for reagent variability
Contact Synexa
In summary, designing and validating GMP grade ligand binding and potency assays requires a deep understanding of regulatory expectations, careful assay design, and ongoing performance monitoring. Avoiding common pitfalls and implementing rigorous validation practices will help ensure assay reliability throughout the product lifecycle.
For more information or to discuss your specific assay needs, contact our team at contactus@synexagroup.com.
