Laboratories across the United States face significant regulatory updates under the Clinical Laboratory Improvement Amendments (CLIA) and the Centers for Medicare & Medicaid Services (CMS). The new mandates include enforcement of digital notification systems (with a phase-in beginning in 2025 and full enforcement by March 1, 2026), refined cytogenetic reporting protocols, and stricter HIPAA-aligned breach reporting, impacting laboratories which must reassess their internal policies and procedures.
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What Are CLIA and CMS Rules?
The CLIA program, overseen by CMS in partnership with the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), regulates U.S. facilities performing laboratory testing on human specimens for health assessment or disease diagnosis, prevention, and treatment (excluding research).
CLIA certification is mandatory for most clinical laboratories and ensures test accuracy, reliability, and timeliness. Reliable test results are critical to patient care, as they form the basis for accurate diagnoses and effective treatment planning.
CMS enforces these standards through inspections, quality assessments, and enforcement actions, including penalties or certificate revocation. CLIA enforcement has steered toward digital modernization in recent years, emphasizing traceability, cybersecurity, and data interoperability.
Key Regulatory Changes in 2025
CMS is transitioning to electronic communications for all CLIA-related notices, including important CLIA updates, electronic fee coupons, certification renewals, and enforcement actions. This follows a successful pilot initiative demonstrating that electronic-only notifications significantly reduced response times and improved documentation accuracy during audits.[1]
Laboratories must now ensure that their contact information in CMS’s QualityNet system is accurate and routinely maintained. Establishing dedicated compliance email inboxes with auditable records will be crucial. In addition, personnel responsible for regulatory correspondence must be trained to monitor and respond promptly to these communications to avoid delays in compliance.
The deadline to switch to email notifications and start receiving electronic CLIA fee coupons and certificates is March 1st, 2026. However, labs must complete registration and testing of their systems during 025 to remain in good standing. Non-compliance could result in delayed certification or additional CMS enforcement actions. After that, paper fee coupons and CLIA certificates will no longer be available.
Another update concerns cytogenetics reporting standardization. Laboratories must have policies and procedures for ensuring patient specimens' accurate and reliable identification.[2]
CMS will strongly encourage, though not yet legally require, all laboratories to adopt updated cytogenetic reporting practices, including the use of standardized nomenclature from the International System for Human Cytogenomic Nomenclature (ISCN) and clearer interpretative narratives for clinicians.[3] Some accrediting bodies such as the College of American Pathologists (CAP) have already moved to make ISCN reporting mandatory. CMS is expected to align with these standards as early as late 2025.
Laboratories must review and update their laboratory information system (LIS) templates to ensure compatibility with these requirements. In addition, staff training should reinforce proper data structuring and interpretation methods to avoid reporting errors that could trigger corrective actions during CLIA inspections.
Recent guidance from CMS now mandates that labs report qualifying data breaches to CMS under HIPAA (Health Insurance Portability and Accountability Act) and through CLIA-specific channels.
The updated CMS framework requires labs to submit parallel reports: one to the U.S. Department of Health and Human Services (HHS) Office for Civil Rights (OCR), and one to CMS via CLIA channels. Breaches must be reported to OCR within 60 days of discovery, and CMS expects concurrent or near-concurrent notification for significant incidents, though exact timing may vary by breach security. To ensure compliance, labs should integrate automated breach-detection tools and develop dual-track reporting protocols that notify OCR and CMS simultaneously. Internal documentation of breach response must be fully traceable and accessible for audit.[4]
Preparation and Risk Mitigation for Compliance Under the New Rules
To meet the demands of the new CLIA and CMS rule changes, laboratories must adopt a proactive, integrated approach to compliance that spans operations, technology, and training, and establish standardized operating procedures that align with the new guidelines.
Training programs must go beyond technical competencies to include regulatory awareness, particularly regarding the new electronic-only CMS communication and breach reporting requirements.
One of the most common compliance failures during audits involves missed or unmonitored electronic communications from CMS, with serious consequences including missed deficiency notices and certification risks. Similarly, using outdated cytogenetic nomenclature or improperly configured LIS templates can lead to citations and broader enforcement scrutiny. According to CMS inspection summaries from 2024, approximately 18% of cited deficiencies were linked to unmonitored notices, incomplete documentation, or outdated LIS templates.
Ensuring that LIS configurations are updated and validated is critical. Regular testing of LIS templates for compliance can prevent errors that might otherwise be flagged during inspections. Internal audits should be used to identify gaps and simulate key compliance scenarios such as breach notifications and documentation retrieval.
Breach reporting also remains a high-risk area that can result in financial penalties and reputational damage. Labs should implement integrated breach response workflows with periodic simulations or tabletop exercises to help assess readiness and ensure regulatory timeframes are met.
In addition, compliance considerations should be embedded in the early stages of new test development or data workflow design to reduce the risk of regulatory violations during implementation or validation phases. This means anticipating documentation needs, traceability requirements, and information security obligations as key elements of operational planning.
Conclusion
The CLIA and CMS rule changes represent more than procedural updates. They represent an opportunity to refine systems, improve transparency, and enhance overall quality of care. They also signal a transformation in how regulatory compliance is integrated into clinical laboratories' everyday operations.
CMS aims to modernize laboratory oversight and close compliance gaps that could affect patient safety and data integrity by shifting toward fully electronic correspondence, enforcing standardized cytogenetic reporting, and tightening breach notification rules.
Laboratories that embrace these changes proactively through internal training, technology upgrades, and coordinated compliance strategies will not only maintain regulatory compliance but also strengthen operational resilience.
References
- www.cms.gov. (2025). Clinical Laboratory Improvement Amendments (CLIA) [Online]. Available: https://www.cms.gov/medicare/quality/clinical-laboratory-improvement-amendments [Accessed 17/06/2025].
- Federal Register. (2025). 42 CFR Part 493 [Online]. Available: https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493 [Accessed 17/06/2025].
- Hastings, R., Moore, S. and Chia, N., (2024). ISCN 2024 - An International System for Human Cytogenomic Nomenclature (2024). Cytogenet Genome Res, 164, 1-224.10.1159/000538512.
- Alder, S., (2025). HIPAA Updates and HIPAA Changes in 2025 [Online]. Available: https://www.hipaajournal.com/hipaa-updates-hipaa-changes/ [Accessed 17/06/2025].