Guest Essay

Dr. Sharon Ehrmeyer returns with an section for our Basic QC Practices series. If you're operating a laboratory in the U.S., there's a government agency out there that wants to regulate you - do you know which one? In this article, Dr. Ehrmeyer details all the various bureaucracies and their regulations. See which rules apply to you!

• HCFA and COLA
• CLIA QC Requirements based on Test Complexity
• Waived tests
• Provider Performed Microscopy
• Moderate Complexity Tests
• High Complexity Tests
• What if a control fails to meet criteria for acceptability?
• JCAHO
• Standards for Quality Control
• CAP
• Guidelines for Quality Control
• References

Please Note: This article was written before 2000. The regulations have changed. The agencies have changed. Dr. Ehrmeyer has written more recent updates to the US regulations. Please consult the CLIA Final Rule section of this website, or look to the latest edition of the Poor Lab's Guide.

If you perform laboratory tests in the US, the government's got you covered! One way or another, you have to comply with the Clinical Laboratory Improvement Amendments of 1988 (CLIA’88), which establish the minimum standards for all laboratory testing, including specific regulations for quality control [1]. You can, however, select the organization that will administer these regulations or administer professional standards that are equivalent to these regulations:

• The Health Care Financing Administration (HCFA) will inspect any size laboratory, including physician office laboratories, for adherence to the CLIA standards;
• The Commission of Office Laboratory Accreditation (COLA) inspects only physicians office laboratories for adherence to COLA standards which closely parallel the CLIA regulations;
• The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) inspects laboratories as part of an overall inspection of a hospital or healthcare organization;
• The College of American Pathologists Laboratory Accreditation Program (CAP-LAP) mainly inspects large laboratories directed by pathologists.

There are other government approved organizations that have standards for laboratories to follow and some states impose specific requirements [2].

Health Care Financing Administration (HCFA) and Commission of Office Laboratory Accreditation (COLA) Requirements for QC

The first part of this discussion focuses on CLIA’88 and COLA regulations [1,3] since COLA's 200 question checklist adheres to the CLIA’88 QC requirements almost exactly. Professional standards administered via CAP and JCAHO are considered later.

CLIA QC Requirements based on Test Complexity

CLIA'88 regulations are based on four categories of test complexity: waived, provider performed microscopy (PPM), moderate complexity, and high complexity. Current information on test complexity can be obtained from the CDC’s web site (http://www.cdc.gov/phppo/dls/testcat.htm [link no longer supported]). Each testing category has different regulatory requirements for personnel, quality control, quality assurance, proficiency testing, etc.

Waived testing

This category requires the least regulation. Under CLIA and COLA, the minimum requirement for anyone performing waived testing is to follow the manufacturers’ directions for QC, and if no directions are included, to follow good laboratory practices. No specific QC requirements are identified. Good laboratory practice would dictate that controls be run and results documented and reviewed for correctness before reporting patient results. The tests that are waived include the following (current September 29, 1997 list of Waived Tests):

• Dipstick or tablet reagent urinalysis for bilirubin, glucose, hemoglobin, ketones, leukocytes, nitrite, pH, protein, specific gravity, and urobilinogen
• Fecal occult blood
• Ovulation tests - visual color comparison tests
• Urine pregnancy tests - visual color comparison tests
• Erythrocyte sedimentation rates - non-automated
• Blood glucose - all glucose monitoring devices cleared by FDA for home use; HemoCue B-Glucose System, and Cholestech L.D.X.
• Hemoglobin - (non-automated) by copper sulfate; (automated) by HemoCue Hemoglobin System
• Hematacrit - all spun microhematocrit procedures, Wampole STAT-CRIT, Separation Technology STI HemataSTAT II and Model C70, StatSpin Technologies CritSpin, and Vulcon Technologies Microspin 24, Protime - ITC (International Techidyne Corp.) and BMC CoaguChek
• H. pylori -- Serim Pyloritek Test Kit, GI Suppy HP-FAST, Quidel QuickVue One-Step for whole blood, Delta West CLOtest, Abbott FlexPack HP, ChemTrak AccuMeter, and SmithKline FlexSure
• Strep A (throat only) Quidel QuickVue In-Line One-Step, Binax NOW, Abbott Signify and SmithKline ICON Sx
• Cholesterol -- Cholestech L.D.X., BMC Accu-Chek InstantPlus, ChemTrak AccuMeter, and J & J ADVANCED CARE
• HDL Cholesterol -- Cholestech L.D.X.
• Triglyceride -- Cholestech L.D.X
• Gastric occult blood -- SmithKline Gastroccult
• Micro albumin -- BMC Chemstrip Micral
• All qualitative color comparison pH testing for body fluid (other than blood)

To keep up to date with all the new test additions and new methodologies for waived tests, you can check the CDC Web site [http://www.cdc.gov/phppo/dls/clia.htm link no longer supported].

Provider Performed Microscopy (PPM)

As of January 1993, the category "Physician-Performed Microscopy" was established under CLIA’88. In the April 24, 1995 Federal Register, the category was renamed to "Provider-Performed Microscopy." This category is a subset of moderate complexity and is exclusively for physicians, dentists, nurse practitioners and midwives, and physician assistants performing the testing as part of a patient examination. The primary instrument for performing the test(s) is the microscope.

The 9 tests identified under a PPM CLIA certificate can be performed, as well as waived tests. When these tests are provided, the practitioners are expected to follow the manufacturers’ directions for QC or follow good laboratory practices. Good laboratory practice would dictate that controls be run whenever possible and results documented and reviewed for acceptability before reporting patient results. The PPM category includes:

• all direct wet mount preparations (suspended in saline or water) for the presence or absence of bacteria, fungi, parasites, and human cellular elements
• KOH preps
• pinworm exams
• fern tests
• post-coital direct qualitative exams of vaginal or cervical mucous
• urine sediment exams
• nasal smears for granulocytes
• fecal leukocyte exams
• qualitative semen analysis (limited to the presence or absence of sperm and detection of motility).

Moderate Complexity Tests

Approximately 75% of all tests performed in laboratories today fall in the category of moderate complexity. For this category, the QC requirements are identified in subpart K for CLIA’88 -- Quality Control. Originally, in the February 28, 1992 Federal Register, HCFA stated that as of September 1, 1994, laboratories would meet most of CLIA'88 QC requirements simply by following manufacturers' labeling, provided the FDA approved manufacturers' QC instructions. This never happened and the implementation date (9/1/94) has now been suspended, in the May 12, 1997 Federal Register, until at least 7/31/98.[5] Until HCFA implements new QC requirements, laboratories performing moderate complexity tests will meet the CLIA QC requirement by following sections §493.1201 and §493.1202(c) only.

Section §493.1201 (general QC: moderate or high complexity testing, or both) states: The laboratory must establish and follow written QC procedures for monitoring and evaluating the quality of the analytical testing process of each method to assure the accuracy and reliability of patient test results and reports.

Section §493.1202(c) identifies the specific requirements for unmodified moderate complexity tests: [1,4]

• follow manufacturer directions;
• have a procedure manual for the method that identifies how to perform the testing and reporting of results;
• perform and document calibration procedures or check calibration at least once every six months;
• assay at least two levels of control materials each day of testing (a run cannot exceed 24 hours) and keep records;
• perform and document any applicable specialty and subspecialty control procedures;
• perform and document remedial actions as specified in §493.1219;
• maintain records of all QC activities for 2 years or 5 years for immunohematology and 10 years for pathology as specified in §493.1221.[4]

As you can see, CLIA QC includes a lot more than traditional statistical QC and defines standards for calibration, procedure manuals, remedial actions and record keeping. Concerning statistical QC, for most moderate complexity tests, the general requirement is to analyze two levels of QC materials on each day of testing. However, for certain tests, i.e., blood gases, hematology and coagulation tests, etc., CLIA requires additional QC:

• Blood gases require, at a minimum, one control sample every 8 hours of testing and a calibrator or control in each run unless the instrument "autocals" at least every 30 minutes.
• Automated hematology and coagulation test systems require two levels of controls every 8 hours of testing and each time a change in reagent occurs.
• Manual cell counts using a hemocytometer must be tested in duplicate and one control is required every 8 hours of operation.
• For manual coagulation testing, each analyst must perform two levels of controls before testing patient samples and with each change in reagent. In addition, patient and control samples must be tested in duplicate.
• With electrophoresis, one control needs to be included in each electrophoretic cell and the control must contain fractions representative of those routinely reported in patient samples.
• For toxicology, each thin layer chromatogrophy (TLC) plate must be spotted with at least one sample of calibration material containing all drug groups reported by the laboratory with TLC, one control must be included in each chamber, and the sample must be processed through each step of patient testing including extraction.
• Qualitative tests with built-in controls are adequate provided the kit has been qualified with at least one positive and negative control. CAP requires one positive (external) and one negative (external) control per day.
• For those methodologies where the manufacturer specifies, surrogate or electronic controls may be used to fulfill the daily QC requirement. In all cases, the appropriate number of controls (two levels per day for most analytes) must be included and the results must be documented and reviewed to ensure the adequacy of the testing process.

In all cases, documentation of both the QC results and the specific remedial action to "out of control results" must be available to the inspector.

High Complexity Tests

This category includes those tests that are modified by the laboratory, developed by a laboratory, or a test classified as high complexity under CLIA. Laboratories under CLIA and COLA also must comply with Section §493.1201 (general QC): The laboratory must establish and follow written QC procedures for monitoring and evaluating the quality of the analytical testing process of each method to assure the accuracy and reliability of patient test results and reports. Section §493.1202 states for each test of high complexity performed, the laboratory must meet all applicable standards of this subpart (subpart K). For statistical QC, laboratories must be in compliance with the following sections:

• §493.1218: Control procedures are performed on a routine basis to monitor the stability of the method or test system; control and calibration materials provide a means to indirectly assess accuracy and precision of patient test results. Control procedures must be performed as defined in this section unless otherwise specified in sections §493.1223 through §493.1285 (these state specific QC requirements for blood gases, hematology, etc.).
• §493.1218(b) for each method that is developed in-house, is a modification of the manufacturer’s test procedure, or is a method that has not been cleared by the FDA as meeting the CLIA requirements for general QC (all highly complex methods), the laboratory must evaluate instrument and reagent stability and operator variance in determining the number, type, frequency of testing calibration or control materials and establish criteria for acceptability used to monitor test performance during a run of patient specimen(s).
• §493.1218(d)(1) The stated values of an assayed control material may be used as the target values provided the stated values correspond to the methodology and instrument employed by the laboratory and are verified by the laboratory.
• §493.1218(d)(2) Statistical parameters for unassayed materials must be established over time by the laboratory through concurrent testing with calibration materials or control materials having previously determined statistical parameters. (The statistical parameters, e.g. mean and SD, for each lot number must be determined through repetitive testing).
• §493.1218(e) Control results must meet the laboratory's criteria for acceptability prior to reporting patient test results. Laboratory criteria for acceptability refers to the particular control limits or control rules chosen by the laboratory.

What if a control fails to meet criteria for acceptability?

Regardless how a test has been classified, the regulations require "remedial action and documentation of this activity. Section 493.1219(b) Remedial actions states that when: "Results of controls and calibration materials fail to meet the laboratory's established criteria for acceptability, all patient test results obtained in the unacceptable test run or since the last acceptable test run must be evaluated to determine if patient test results have been adversely affected and the laboratory must take remedial action necessary to ensure the reporting of accurate and reliable patient test results.

Joint Commision on Accreditation of Healthcare Organizations (JCAHO) Requirements for QC

The requirements identified for CLIA’88 and COLA also are applicable to JCAHO. Under JCAHO [6], the goal of QC is to achieve quality in laboratory testing and produce the best possible test results and outcomes. Additional JCAHO requirements are found for the different test classification categories.

JCAHO and Waived Testing

JCAHO recognizes waived tests as defined by CLIA'88, but identifies additional QC requirements that include:

• Defined QC checks that at least meet the minimum manufacturer's recommendations (when no QC requirement is specified, the testing institution must define a policy);
• Maintenance of appropriate QC and test records;
• Proof of training and continued competence of all testing personnel;
• Proof all testing personnel have access to current written procedures for QC and remedial actions.
• Maintenance of QC records, including a mechanism to correlate or link analyst, QC records, instrument and instrument problems, and individual patient test results.
• For glucose, at a minimum two levels of controls are required each day a glucose is performed. QC is focused on each meter used, not each individual performing the test. Therefore, not all testing personnel need to routinely perform QC, but each meter must be validated by QC before testing patient samples.

JCAHO and Moderate Complexity Tests

For moderate complexity tests, JCAHO, for the most part, follows CLIA'88 and mandates the same seven QC requirements as CLIA’88 and COLA and also accepts electronic controls for now. However, for use of electronic controls, JCAHO requires that the laboratory verify the manufacturer’s QC claims and run external (usually liquid) controls periodically to validate that no change occurred with the testing system.

JCAHO and High Complexity Testing

Testing sites must follow all the CLIA QC requirements for high complexity tests as well as for any modified moderate complexity tests (this includes not following the manufacturer’s directions) and tests developed in-house.

JCAHO Standards for Quality Control

In addition to the requirements identified above, JCAHO requires that all testing sites meet the following standards associated with quality control.

General QC Requirements:

• (QC.1) Each specialty and subspecialty (of testing) has a documented quality control program.
• (QC.1.3) The laboratory’s QC system includes daily surveillance of results by appropriate personnel.
• (QC.1.4) The laboratory takes remedial action for deficiencies identified through QC measures or authorized inspections and documents such actions.
• (QC.1.5) The laboratory ensures that QC results meet its criteria for acceptability before it reports patient test results.

Clinical Chemistry QC Requirements:

• (QC.6) Using appropriate controls, the laboratory verifies each procedure in clinical chemistry at least once each day of use.
• (QC.6.2) Using repetitive testing, the laboratory establishes control ranges with valid statistical measurements for each procedure in chemistry.
• (QC.6.3) The laboratory has established and makes available to its staff acceptable limits for all standard and reference QC samples, as well as the action to take when results are outside satisfactory control limits.
• (QC.6.4) The laboratory established test control limits to provide results with meaningful clinical applications.

Hematology and Coagulation QC Requirements:

• (QC.7.1) The laboratory verifies each procedure and test parameter against known standards or controls within the range of clinically significant values each day of use.
• (QC.7.3) The laboratory has established and makes available to its staff acceptable limits for all standard and reference QC samples, as well as the action to take when results are outside satisfactory control limits.
• (QC.7.4) The laboratory has established test control limits to provide results with meaningful clinical applications.

College of American Pathologists Laboratory Accreditation Program (CAP-LAP) Requirements for Quality Control

CAP-LAP's philosophy is that all clinical laboratory tests need to follow the requirements defined for high complexity testing under CLIA'88 [7]. Requirements for routine analysis of QC follow the CLIA requirements in terms of number and frequency, except controls must be included with all tests (even those identified as waived tests under CLIA'88). For now, CAP only allows "acceptable" alternative (electronic) QC for point of care testing. The latest POCT Checklist (Checklist 30, 1997.0) states that certain unit-use devices/kits may warrant some combination of instrument, procedural, and/or electronic controls. Question 30.0550 (Checklist 30) states that POCT sites using alternative QC must have scientifically acceptable evidence (documented information) that the entire analytical process is being evaluated correctly. Except for electronic controls, CAP requires that control specimens be tested in the same manner as patient samples.

Qualitative tests (even those with built-in controls) need to be evaluated with both a positive and negative control each day of use. For all tests, CAP-LAP requires an audit trail that ties the patients’ results with the analyst, instrument and QC. In addition, the QC program should show evidence of documented review on the next shift, if no supervisor is on site, and at least weekly review by the technical supervisor and monthly secondary review by the director or director's designee.

CAP Guidelines for Quality Control

In the general requirements, CAP states in Checklist #1 1997.1 that the overall QC program for the entire laboratory must be clearly defined and documented. It must include general policies and delegation of responsibilities. The QC records should be well-organized with a defined system to permit regular review by appropriate supervisory personnel.

• 01.3000) Does the QC program clearly define goals for monitoring analytic performance, procedures, policies, tolerance limits, corrective action and related information?

Hematology QC Requirements (Checklist 2, 1996.2)

• (02.2005) For numeric data generated by the hematology laboratory, are Gaussian or other longitudinal process control statistics (S.D. and C.V.) calculated at least at monthly intervals to define analytic precision?
• (02.2010) Are tolerance limits (numeric and/or non-numeric) fully defined and documented for all hematology and coagulation control procedures?
• (02.2580) Does the laboratory use preserved or stabilized whole blood preparations for longitudinal process control?
• (02.2582) Does the laboratory use retained, previously analyzed patient whole blood samples for longitudinal process control?
• (02.2587) If assayed controls are used for CBC instruments, do control values correspond to the methodology and have target values been verified by the laboratory for quantitative tests?
• (02.2588) If unassayed controls are used, has a statistically valid target range been established for each lot by repetitive analysis in runs that include previously tested control materials?

Automated/General Chemistry QC Requirements (Checklist 3, 1996.2)

• (03.2600) For quantitative tests, are control specimens (with a matrix appropriate for the method) at more than once concentration (when available) used for all tests with each analytical run?
• (03.2605) If assayed controls are used, do control values correspond to the methodology and have target values been verified by the laboratory for quantitative tests?
• (03.2610) If unassayed controls are used, has a statistically valid target range been established for each lot by repetitive analysis in runs that include previously tested control materials?
• (03.2625) Are tolerance limits defined for control procedures? Note: For tests with numeric results, recovery ranges supplied by manufacturers of assayed controls must not be substituted for QC range limits determined the laboratory on its own equipment.

References

1. U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA programs: Regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Final rule. Fed Regist 1992; 57:7002-186.
2. Laessig RH, Ehrmeyer SS: New Poor Man’s (Person’) Guide to Meeting the Regulations. R & S Consultants, Madison WI. 1997.
3. Accreditation Manual. Commission on Office Accreditation (COLA). Columbia, MD, 1996.
4. U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA programs: Regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and Clinical Laboratory Act program fee collection. Fed Regist 1993:58:5215-37.
5. U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA Programs: Extension of Certain Effective Dates for Clinical Laboratory Requirements Under CLIA. Fed Regist 1997;62:25855-58.
6. Accreditation Manual for Pathology and Clinical laboratory Services. Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Oakbrook Terrace, IL, 1996.
7. Laboratory Accreditation Program. College of American Pathologists (CAP). Northfield, IL, 1997.

Biography: Sharon S. Ehrmeyer, Ph.D.

Sharon Ehrmeyer, Ph.D., MT(ASCP) is Professor of Pathology and Laboratory Medicine and Director of the Medical Technology Program at the University of Wisconsin in Madison, Wisconsin. Dr. Ehrmeyer is active in the American Association for Clinical Chemistry, the American Society for Clinical Laboratory Science and the National Committee Clinical Laboratory Standards where she serves on the Board of Directors and chairs its pH/Blood Gas Committee. Dr. Ehrmeyer gives numerous presentations on laboratory regulations (CLIA, JCAHO, CAP and COLA), point of care testing and various quality issues. Her research interests focus on clinical laboratory quality and the impact of government regulations on laboratory practices.