While clinical genomics labs (those running NGS-based laboratory developed tests) are not currently subject to FDA oversight, that doesn’t mean they won’t be someday. The question is, how soon will that day come and, when it does, will your lab be ready?
The Current State of LDT Regulations
Laboratory developed genomics tests are already subject to CAP and CLIA guidelines. And as they gain in popularity, usefulness, and complexity, the FDA is taking more of an interest in regulating them.
“The FDA has identified problems with several high-risk LDTs including: claims that are not adequately supported with evidence; lack of appropriate controls yielding erroneous results; and falsification of data. The FDA is concerned that people could initiate unnecessary treatment or delay or forego treatment altogether for a health condition, which could result in illness or death.”
This January, after a few years of gathering data and comments from stakeholders, the FDA released a “discussion paper” regarding regulation of LDTs. For NGS-based tests, specifically, the FDA released draft standards in July 2016 for “Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases.”
Neither of these documents is enforceable. But they do give some indication as to what shape FDA regulation might take should it ever arrive.
Is FDA Regulation Imminent?
With the new presidential administration, the FDA announced it would be holding back on its plans to regulate LDTs. But for how long is unknown.
The debate revolves around whether the FDA has the authority to regulate LDTs as “medical devices.” It’s a “legally untested assertion,” as some experts claim. For a look at both sides of the issue, read a point/counterpoint by our own experts.
If and when FDA regulation does come, if your lab isn’t ready, it could suffer. Your work could be disrupted, your career threatened, and your business put at risk.
- You would have to revamp your entire infrastructure. Large commercial labs may be more prepared for this than smaller academic ones.
- You may need to replace employees who aren’t up to the compliance challenge.
- You would face a competitive disadvantage against FDA-approved labs.
But whether FDA regulation comes tomorrow, next year, or not at all (highly unlikely), many of its recommendations, especially those around quality control and running controls, are best practices any lab should follow to protect the accuracy of its results.
Here are three tips for strengthening your lab’s quality control practices and readying yourself for whatever regulations the FDA may throw at you.
1. Don’t Make Assumptions or Follow the ‘Community-Set’ Bar
Instead of confirming it for themselves, too many labs make assumptions about the quality and accuracy of their tests.
For example, you might say to yourself, “If we can detect X (something difficult to detect), we can detect Y (something ‘easy’ to detect).” But if you make this assumption, you may not know what you’re missing. The complexities involved with clinical genomics testing require both common, easy-to-detect variation to be routinely examined as well as rare and difficult-to-detect ones.
Another erroneous assumption labs make is that practices that are generally accepted in the genomics testing community are good enough. For example, “I validated this test once. I can assume it’s accurate six months later.” Both assays and instrumentation may drift in their performance, and you want to be able to regularly evaluate this.
But regardless of where the community sets the bar, the FDA may set it higher. And regulations aside, if you set your standards too low, you risk the fidelity your results.
2. Run Controls With Quality Reference Materials
In its standards for NGS labs, the FDA recommends running controls:
“Specify controls and reference materials for achieving confidence in the test. These should include per sample, per run, etc., as needed, in order to establish the quality of performance. They can also include gene and disease specific controls for detecting common pathogenic variants used to diagnose well-defined diseases or other conditions, pan-disorder positive controls (most common pathogenic variants), and other appropriate controls and reference materials.”
It’s very likely these recommendations would make it into whatever final regulations the FDA comes out with. But the FDA isn’t specific about what it considers high-quality controls.
We recommend using reference material that is:
- Highly-multiplexed, able to detect a wide range of mutations and variants.
- Patient-like, as close to patient samples as possible.
Learn more about running controls with high-quality reference material in our whitepaper, “2 Tools For Overcoming Your Clinical Lab's Toughest Quality Control Challenges.”
3. Implement Robust Design Controls
The FDA is, at the most basic level, an agency that regulates manufacturers. As such, the first thing it might do to regulate LDTs is require them to comply with 21 CFR 820 Quality System Regulation, the FDA rules governing the manufacture of medical devices. What this means for your lab is the FDA will expect you to implement a robust quality management system.
There are two hallmarks of a robust quality management system:
- High-quality, highly-multiplexed reference materials, as discussed above.
- The effective use of quality control metrics for monitoring the health of your assays.
But you’ll also need to keep all this information organized and accessible, especially if FDA auditors come calling.
Different labs use different strategies to track their metrics, from paper hardcopies to powerful-but-complex laboratory information management systems. We offer our own easy-to-use software product, designed especially for genomics testing laboratories. Read more about SeraCare’s iQ NGS QC Management Software here.
Are you ready to futureproof your lab? Start by clicking below for your free copy of our whitepaper, “2 Tools For Overcoming Your Clinical Lab's Toughest Quality Control Challenges.”