Fit for Purpose: Ensuring Rigorous Validation in a GMP Environment

In the complex world of cell and gene therapy, the reliability of every analytical result depends on one essential principle: validation. Within C3i’s GMP framework, each assay, instrument, and dataset must demonstrate that it is fit for purpose, capable of delivering accurate, traceable, and reproducible results that withstand regulatory scrutiny, ensuring Rigorous Validation in a GMP Environment.

Method qualification and validation sit at the heart of Quality Control (QC). These processes are what ensure that the data supporting product release is scientifically sound and compliant with international standards. Working within a robust Quality Management System, C3i monitors every dimension of the lab environment, from reagent traceability to equipment qualification and data integrity, in accordance with 21 CFR Part 11. The goal is to ensure that every step, from sample handling to electronic record management, including personnel training, is fully auditable and compliant with relevant regulations.

To be validated, a method must meet a range of performance characteristics defined by the International Council for Harmonization (ICH). These include accuracy, precision, specificity, robustness, and reproducibility. However, in a rapidly evolving therapeutic landscape, validation must also be strategic. The art lies in determining what parameters are truly critical for the intended purpose, balancing scientific rigour with operational efficiency.

Robustness plays a significant role. Assessing how variables like time, temperature, or matrix composition influence assay performance helps maintain confidence in the results, even under real-world conditions. This robustness ensures that testing remains reliable as new materials, reagents, and technologies are introduced into the pipeline.

A compelling example of this approach is C3i’s mycoplasma testing validation. Traditional compendial methods, such as USP <63>, require 28 days of culture to confirm sterility. C3i’s team implemented a real-time PCR–based assay capable of detecting over 200 species within one day, representing a significant gain in speed for time-sensitive cellular products. To demonstrate equivalence, the method underwent a three-tier validation process:

1. Instrument and software qualification (IOQ/PQ) with electronic audit trail verification under 21 CFR Part 11.
2. Method qualification and performance validation, ensuring specificity and sensitivity matched reference culture methods.
3. Matrix validation, confirming that the presence of the cell therapy product itself does not inhibit detection.

By aligning the validation strategy with regulatory expectations, the team achieved comparability with culture-based testing while drastically reducing turnaround time, allowing patients to access treatment more quickly without compromising safety or accuracy.

Beyond initial qualification, C3i maintains ongoing performance monitoring to ensure validated assays remain consistent over time. This includes trending results across reagent lots, instruments, and monitoring biological variability, critical in a field where each cell therapy product is unique.

Ultimately, the validation process brings together science and discipline. It’s about anticipating variability, documenting every detail, and revisiting assumptions as methods and regulations evolve. At C3i, that mindset of continuous improvement defines the Quality Control philosophy: being fast when it matters, rigorous where it counts, and always fit for purpose.

This article is drawn from material presented during the webinar Cellular Therapy Product Release Testing within a GMP context, presented on October 16th 2025, by C3i’s experts Ann Brasey (Principal Scientist), Pauline Cassart (QC Technical Supervisor), and Ludovic Durrieu (QC Operations Manager).