How Often to Run QC Under CLIA
For most nonwaived quantitative tests the answer is two control levels each day you test patients. Then the exceptions start: coagulation and blood gases every 8 hours, events that call for controls before the next patient, package inserts that ask for more, and IQCP, which lets a lab set its own schedule. Each rule below is quoted from 42 CFR 493 or CMS. Once the results are in, the QC statistics calculator turns them into a monthly summary.
The short answer
For most nonwaived quantitative tests CLIA's floor is two control materials of different concentrations each day you test patients. Some specialties ask for more, the manufacturer can ask for more, and an Individualized Quality Control Plan (IQCP) can set a different schedule. Never less than the package insert.
Quick reference
- Quantitative test, each day patients are tested2 levels, § 493.1256(d)(3)(i)
- Qualitative test, each day patients are testedneg + pos, (d)(3)(ii)
- Nonmanual coagulation2 levels each 8 h, § 493.1269(b)
- Blood gases1 control each 8 h, § 493.1267(b)
- After a reagent change or major maintenancebefore patients, (d)(6)
- Waived testspackage insert, § 493.15(e)(1)
The CLIA minimum: two levels each day of testing
At least once each day patient specimens are assayed or examined perform the following for— (i) Each quantitative procedure, include two control materials of different concentrations; (ii) Each qualitative procedure, include a negative and positive control material
Read the clock in that sentence closely: it is each day patient specimens are tested, not each calendar day. A physician office lab that runs its chemistry analyzer Monday, Wednesday and Friday runs its two levels on those three days. A day with no patients needs no controls; the first patient of the next day does.
“Two control materials of different concentrations” means two levels, not the same vial run twice. The rest of § 493.1256(d) sets the minimum for other kinds of procedure, all once each day of testing unless noted:
| Procedure | Minimum controls | § 493.1256 |
|---|---|---|
| Quantitative (a number) | Two control materials of different concentrations | (d)(3)(i) |
| Qualitative (positive or negative) | A negative and a positive control material | (d)(3)(ii) |
| Graded or titered results | A negative control and one with graded or titered reactivity | (d)(3)(iii) |
| Has an extraction phase | Two controls, one able to detect extraction errors | (d)(3)(iv) |
| Molecular amplification | Two controls, plus an inhibition control where inhibition can cause false negatives | (d)(3)(v) |
| Thin layer chromatography | A calibrator spotted on each plate or card, and at least one control on each | (d)(4) |
| Electrophoresis | At least one control run with the patient specimens | (d)(5) |
The whole list applies “Unless CMS approves a procedure, specified in Appendix C of the State Operations Manual … that provides equivalent quality testing”. That procedure is IQCP, covered below.
Where the rules ask for more than once a day
The daily minimum gives way to “the additional specialty and subspecialty requirements at §§ 493.1261 through 493.1278” (§ 493.1256(d)(1)). For a small lab, the ones that change the clock are in hematology and blood gases:
| Test | Requirement | Cite |
|---|---|---|
| Nonmanual coagulation | Two levels of control each 8 hours of operation and each time a reagent is changed | § 493.1269(b) |
| Manual coagulation | Each person testing runs two levels before patient samples and at each reagent change; patients and controls in duplicate | § 493.1269(c) |
| Manual cell counts (hemocytometer) | One control each 8 hours of operation; patients and controls in duplicate | § 493.1269(a) |
| Blood gases | One control each 8 hours of testing, low and high values both covered each day, and one each time specimens are tested unless the analyzer verifies its calibration at least every 30 minutes | § 493.1267(b), (c) |
Takeaway
Events that call for controls before the next patient
Some QC is triggered by what happens to the analyzer, not by the calendar. Under § 493.1256(d)(6), run controls “before resuming patient testing” when:
- a complete change of reagents is introduced;
- major preventive maintenance is performed; or
- any critical part that may influence test performance is replaced.
Two more rules shape who runs the controls and how. Over time, “rotate control material testing among all operators who perform the test” ((d)(7)), and test controls “in the same manner as patient specimens” ((d)(8)): the same handling and loading as the patients, with no extra care taken over the vial.
Calibration verification is a separate clock. It runs “At least once every 6 months” and after the same kinds of events, and also when controls show an unusual trend or shift (§ 493.1255(b)(3)). Passing the daily controls does not reset it.
When the manufacturer asks for more
CLIA's daily minimum is a floor, and the package insert can raise it. The lab must “perform control procedures using the number and frequency specified by the manufacturer or established by the laboratory when they meet or exceed” the daily minimum (§ 493.1256(d)(2)). If the insert says to run controls with every new cartridge lot, every shipment or every so many hours, that is your schedule.
The acceptability criteria stack the same way: control results must meet “the laboratory's and, as applicable, the manufacturer's test system criteria for acceptability before reporting patient test results” (§ 493.1256(f)). And the number, type and frequency of controls are the lab's to set from the performance it verified when it brought the test in ((b), § 493.1253(b)(3)), so a method that verified with poor precision may need more than the floor.
CMS's IQCP Workbook puts it in one line: “Laboratories cannot establish QC procedures that are less stringent than those specified by the manufacturer of the test system.”
Takeaway
When IQCP replaces the default
CMS describes an Individualized Quality Control Plan as “an alternative quality control option permitted under CLIA” (CMS IQCP page). It is the procedure in Appendix C of the State Operations Manual that the daily minimum's opening words point to. IQCP is CMS's current alternative QC option; under it the lab, not the two-levels-a-day rule, sets the frequency, through three parts: Risk Assessment, Quality Control Plan and Quality Assessment.
The workbook is plain about the choice: “The IQCP approach is voluntary. If you do not choose to adopt an IQCP, your laboratory must test two levels of external controls on each test system for each day of testing”. It covers nonwaived testing in every CLIA specialty and subspecialty except pathology.
The typical reason to write one is a test system whose own QC is built in. The workbook's example is a magnesium analyzer whose instructions recommended external QC less often than CLIA requires, with an internal control on every reagent disc. The lab's risk assessment covers at least five components: specimen, test system, reagent, environment and testing personnel. The IQCP risk assessment worksheet walks those five components for one test system.
IQCP does not mean less QC by default
The plan must state “the number, type, and frequency of testing control materials” and require QC as the manufacturer specifies, “but not less than the manufacturer's instructions”. The workbook adds that adopting IQCP “will not necessarily reduce your QC testing practices”.
Waived tests: the package insert sets the schedule
None of the above binds a waived test. A lab with a certificate of waiver must “Follow manufacturers' instructions for performing the test” (§ 493.15(e)(1)), so the QC frequency on the insert is the requirement: if it says to run the external controls with each new kit lot or shipment, that is the rule. IQCP is for nonwaived testing only; a waived test does not need one.
When a control fails
A control that fails the lab's criteria stops the run: results are acceptable only “before reporting patient test results” (§ 493.1256(f)). Which result counts as a failure is the lab's written rule, often a set of Westgard rules read on a Levey-Jennings chart.
The rule itself (§ 493.1282(b)(2)): “All patient test results obtained in the unacceptable test run and since the last acceptable test run must be evaluated to determine if patient test results have been adversely affected.”
That look-back is why frequency matters beyond compliance. With controls once a day, the last acceptable run can be yesterday morning, and every patient since is in scope. More frequent controls on a busy analyzer shrink the number of patients a failure puts in question.
Keeping the record
“The laboratory must document all control procedures performed” (§ 493.1256(g)), and QC records are kept “for at least 2 years” (§ 493.1105(a)(3)). Check the control log against the days patients were tested: a testing day with no controls recorded is a gap in the record.
At month end, summarise each level's mean, SD and CV with the QC statistics calculator and file it with the charts. A lab that wants the schedule, the charts and the summaries kept for it can compare laboratory QC software, and peer comparison data in Bio-Rad Unity alternatives.
Takeaway