Who Regulates What: CMS, FDA, CAP, TJC, CLSI

The layers

U.S. molecular labs answer to several bodies with different jobs:

CLIA and CMS

The Clinical Laboratory Improvement Amendments of 1988 (CLIA) set quality standards for all human testing for diagnosis, prevention, or treatment, wherever it’s performed ¹. The regulations are at 42 CFR Part 493, including the performance-specification rules covered in the last lesson ².

CMS issues one of several certificates:

• Certificate of Waiver (waived tests only).
• Provider-Performed Microscopy.
• Certificate of Compliance (inspected by the state agency for CMS).
• Certificate of Accreditation (inspected by an approved accreditor).

CLIA has no separate molecular specialty; molecular tests fall under general requirements and the relevant specialties, and most are high complexity, which sets personnel qualifications (laboratory director, technical supervisor, testing personnel) ¹.

FDA

FDA regulates the manufacturers of IVD kits, instruments, and ASRs under the Food, Drug, and Cosmetic Act: clearance and approval, labeling (including the ASR, RUO, and IUO statements), quality system rules, and adverse event reporting. It also assigns each commercial test a CLIA complexity. FDA’s attempt to regulate LDTs as devices was vacated in 2025, so lab-developed tests are governed by CLIA ³.

Accreditation

Most molecular labs choose accreditation over state-agency inspection:

• CAP (College of American Pathologists) is the main accreditor for molecular labs. A peer team inspects every two years, and the lab completes a self-inspection in the alternate year ⁴. Labs are inspected against the checklists matching their testing: Laboratory General, All Common, and discipline checklists including Molecular Pathology (MOL) ⁴. CAP requirements are often stricter and more specific than CLIA’s: the carryover, thermocycler, and cut-off rules quoted earlier in this course are MOL checklist items ¹.
• The Joint Commission (TJC) accredits many hospital laboratories along with the hospital.
• COLA accredits many physician office and smaller labs.

Accreditation also usually requires participation in the accreditor’s proficiency testing.

CLSI

The Clinical and Laboratory Standards Institute publishes consensus documents that define good practice. Molecular labs use the MM series (for example, MM19 on establishing molecular testing in clinical lab environments) and the EP evaluation protocols (EP17 for detection capability, EP05 for precision, among others). They aren’t law, but inspectors expect labs to follow them or justify an alternative.

States and others

• New York State requires its own approval (through the Clinical Laboratory Evaluation Program) for any lab testing New York residents’ specimens, including review of LDTs ¹.
• Washington and California license labs.
• ISO 15189 accreditation (medical laboratory quality and competence) is used by some labs, especially those working internationally ¹.

What to take from this

CLIA is the law, at 42 CFR 493, and CMS enforces it through certificates and inspections. FDA regulates manufacturers and IVDs and sets CLIA complexity, but not LDTs after 2025. CAP accreditation, with inspections every two years and the Molecular Pathology checklist, is the norm for molecular labs, alongside TJC and COLA. CLSI writes voluntary standards that inspectors rely on, and New York and a few other states add their own requirements.