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In regulated laboratory environments, validation is a crucial step for ensuring the reliability and integrity of scientific data. Two key types of validation often come into play: assay validation and computer system validation (CSV). Each type serves a distinct purpose. However, how they are applied varies across industries, based on the nature of the lab’s work, the particular regulatory standards that apply, and the lab’s risk tolerance.
Assay validation is the process of demonstrating that a lab method or test (the assay) performs as intended and produces consistent, accurate, and reproducible results. This is a cornerstone of lab quality systems, particularly for labs regulated by agencies like the U.S. Food and Drug Administration (FDA).
Assay validation typically evaluates the following characteristics:
Before an assay can be used in a regulated setting, such as for clinical trials, product release, or quality control, it must be validated. This ensures confidence in the results generated and supports data integrity and regulatory compliance.
Computer system validation (CSV) is the process of verifying and documenting that a software application or computer system performs reliably according to its intended use and regulatory requirements. In a lab setting, this includes computer systems that collect, process, or report data related to validated assays.
Examples of systems requiring CSV include:
CSV ensures that the software supporting lab operations does not introduce errors or compromise the integrity of scientific data.
Assays and their supporting software systems can be closely linked in labs. For example, a high-performance liquid chromatography (HPLC) assay may rely on chromatography software for data collection and analysis, or a sequencing lab might use a bioinformatics data pipeline to transform raw reads into lists of sequence variants, gene expression profiles, or other relevant data. This interdependency means that both the assay or sequencing data and the software system require validation to ensure the overall process is trustworthy.
This relationship raises an important operational question. Is it better to validate the assay and the system separately, or together as a single package?
Often, labs choose to validate the assay separately from the computer system that supports it. Each validation effort has its own documentation, testing strategy, and acceptance criteria.
The benefits of the separate approach are twofold:
However, the separate approach is not without its challenges. It requires careful documentation to prove that the assay’s integrity is maintained across systems. And it demands more upfront effort to ensure there is appropriate interfacing between the assay and system validations.
With a combined approach, labs validate the assay and its supporting computer system together as a single unit or workflow. This can simplify the process, especially when computer systems are stable and unlikely to change over time.
The benefits of the combined approach include:
There are several challenges, however. For example, the combined approach can lead to rigidity. Any future change to the computer system — no matter how minor — could trigger the need to revalidate the entire package, including the assay. There’s also the risk of dependency when the validation status of the assay is tied to the software environment, which may limit flexibility.
The decision to separate or combine validations depends on several factors:
This last point is critical because the regulatory environments governing some sectors demand the separation of validation activities.
A strict separation of assay validation and CSV is common for labs operating within GxP environments that must adhere to regulations such as FDA 21 CFR Part 11, ICH guidelines (Q2 for assays), or GAMP 5 for systems.
These labs often use risk-based validation frameworks to determine the scope of testing and documentation. This can result in a high level of compliance assurance with a clear audit trail and documentation for both assay performance and system integrity. It also allows independent upgrades of systems without invalidating assay work. Nevertheless, it can be resource-intensive and documentation-heavy, as well as requiring strong coordination between QA, IT, and lab teams.
Labs developing medical devices, which are regulated by the FDA and ISO 13485, typically lean toward combined validation when software is custom-built or embedded. That’s because assay and device software may be co-developed and co-validated, particularly for companion diagnostics or in vitro diagnostic (IVD) tools. In this scenario, labs might use medical device software lifecycle models, like IEC 62304, in parallel with assay validation.
One benefit of this approach is that bundling validations into a single product lifecycle leads to less duplication. It’s also ideal for purpose-built, stable systems where assay and software are interdependent. Downsides include the fact that any software change can trigger a full revalidation, and there is less flexibility to evolve software independently of the assay.
Labs in this category tend to combine validations or use less formal CSV processes, especially if operating under ISO 17025 rather than FDA regulations. Their focus is on method validation, with systems validated for fitness-for-use rather than full CSV protocols.
A combined approach can mean lower cost, reduced complexity, and easier adoption of off-the-shelf systems with minimal customization. But it can lead to potential gaps in data integrity controls if CSV rigor is low.
In the more heavily regulated clinical lab environment, with regulations such as CLIA, CAP, and ISO 15189, emphasis is on laboratory-developed test (LDT) validation. CSV expectations are rising, however, especially with the use of artificial intelligence/machine learning (AI/ML) tools, middleware, and advanced analytics. In these labs, integrated workflows — such as those between instruments, software, and an assay — might require validation.
Clinical labs prefer to implement streamlined workflows and consolidated documentation to meet clinical turnaround and performance needs efficiently. But, combined validations can lead to rigid systems, a challenge in an evolving regulatory landscape with shifting requirements.
Industrial, academic, and R&D labs often implement fit-for-purpose validation, with flexible or minimal CSV, depending on the intended use of data. Academic and early-stage research labs may not perform formal validations until they move to a regulated environment.
This lack of formal validation and lower compliance overhead gives labs greater agility and potential for innovation. However, it does result in a risk of inadequate traceability and reproducibility if processes aren’t standardized, so the work is not suitable for regulated submissions.
In practice, labs often find that a hybrid approach is necessary. As lab processes grow more complex, they rely on an increasing number of computerized systems to run assays — some of which are more critical than others.
For example, certain systems, such as those integrated with medical devices, are so essential to assay execution that the assay cannot be performed without them. In these cases, assay validation must be done in tandem with CSV. However, the same assay may also use less integral systems, where CSV can be conducted separately.
An experienced consultant can help labs understand the nuances of their unique situation and determine whether validation should be separate or combined, or whether a hybrid approach is the most efficient way to meet regulatory requirements while keeping things as simple as possible.
Assay validation and computer system validation are both critical to ensuring scientific and regulatory integrity in a lab. While they serve different purposes, they often work in tandem. Whether you choose to validate them separately or as a combined process, or use a hybrid approach, depends on your lab’s needs and system complexity, how often you expect changes to occur, and most importantly, the regulatory oversight in your sector.
The key is to ensure that each component — be it an assay or the informatics system — is thoroughly validated for its intended use, with appropriate controls in place. A thoughtful validation strategy not only supports compliance but also enables agility and confidence in your laboratory operations.
Call us to understand the optimal approach for your lab.
