Quality Regulations
- the 2002 UpdateQuality Regulations
- the 2002 UpdateIf 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 performance standards for all laboratory testing, including specific regulations for quality control [1]. You can, however, select to follow the standards from government-deemed (approved) organizations that have standards equivalent to the CLIA regulations:
- The Centers for Medicare and Medicaid Services (CMS), formerly known as the Health Care Financing Administration (HCFA), will inspect any size laboratory, including physician office laboratories, for adherence to the CLIA standards;
- COLA, formerly known at the Commission of Office Laboratory Accreditation, inspects physicians office laboratories and small hospitals 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 Laboratory Accreditation Program of the College of American Pathologists (LAP-CAP) 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].
The first part of this discussion focuses on CLIA’88 (CMS) and COLA requirements [1,3] since COLA’s self-inspection and inspection checklist almost exactly adheres to the CLIA’88 QC requirements. Professional standards administered via CAP and JCAHO are considered later.
CLIA’88 regulations are based on the test complexity or the difficulty to perform the test methodology. There are three categories of test complexity: waived, moderate, and high. Provider-Performed Microscopy (PPM), discussed later, is a subset of the moderate complexity category. Current information on test complexity can be obtained from the CDC’s web site (http://www.phppo.cdc.gov/clia/default.asp). Each testing category has different regulatory requirements for personnel, quality control, quality assurance, proficiency testing, etc.
This category has the least regulation. Under CLIA and COLA, the minimum requirement for anyone performing waived testing is to follow manufacturers’ directions including those specified for QC. If the manufacturer identifies no specific QC requirements, then testing sites are expected to follow good laboratory practices, which usually dictate that controls be run and results documented and reviewed for correctness before reporting patient results. The list of waived tests continues to expand and now includes methodologies for more than 50 analytes. The most current list can be viewed on CDC’s website under the section on test complexities.
In January 1993, CMS established the category “Physician-Performed Microscopy [4].” This category is a subset of moderate complexity and is exclusively reserved for physicians, dentists, nurse practitioners and midwives, and physician assistants performing the testing as part of a patient examination. In the April 24, 1995 Federal Register, the category was renamed to “Provider-Performed Microscopy [5].” The primary instrument for performing PPM tests is the microscope.
The 9 tests identified below as well as all the waived tests can be performed under a PPM CLIA certificate. The practitioners are expected to follow the manufacturer’s directions for QC and follow good laboratory practices. 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).
Approximately 75% of all tests performed in laboratories fall in the moderate complexity category. The QC requirements are identified in subpart K, sections §493.1201 and §493.1202(c) in the February 28, 1992 Federal Register. The remaining sections in subpart K, at least until December 31, 2002, apply only to high complexity testing [6].
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 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;
- perform and document control procedures using at least two levels of control materials each day of testing (a run cannot exceed 24 hours);
- perform and document any applicable specialty and subspecialty control procedures as specified under §493.1223;
- 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
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.
- For those methodologies where the manufacturer specifies, surrogate or electronic controls may be used to fulfill the daily QC requirement provided manufacturer’s directions are followed.
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.
This category includes those tests that are modified (not following the manufacturer’s directions) by the laboratory, developed in-house, or a test classified as high complexity under CLIA. Laboratories under CMS (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(a) states for each test of high complexity performed, the laboratory must meet all applicable standards of subpart K, which includes sections §493.1201 and §493.1203-1285. 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.
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.”
The requirements identified for CMS (CLIA) also are applicable to JCAHO. Under JCAHO, the goal of QC is to achieve quality in laboratory testing and produce the best possible test results and outcomes.
JCAHO recognizes waived tests as defined by CLIA’88, but identifies additional quality and 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 for each glucose meter used. QC is focused on the meter, not the individuals performing the test. Therefore, not all testing personnel need to perform QC routinely, but QC must validate each meter before patient samples are tested.
For moderate complexity tests, JCAHO, for the most part, follows CLIA’88 and mandates the same seven QC requirements as CMS (CLIA). JCAHO also accepts electronic controls, however, before electronic controls can be used routinely, JCAHO requires that the laboratory verify the manufacturer’s QC claims. In addition, JCAHO requires that external (usually liquid) controls be run periodically to validate that no change occurred with the testing system.
Testing sites must follow all the CMS (CLIA) QC requirements for high complexity tests, including modified moderate complexity tests and tests developed in-house.
In addition to the CMS (CLIA) requirements for QC, JCAHO requires that all testing sites performing moderate and high complexity testing meet the following standards associated with QC.
General QC Requirements:
- (QC.1) Each specialty and subspecialty (of testing) has a documented QC 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 has 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.
LAP-CAP’s philosophy is that all clinical laboratory tests, regardless of the CMS test complexity classification, need to follow the same quality requirements. For QC, these are generally the same as those defined by CMS for high complexity testing under CLIA’88. In some cases LAP-CAP requires more controls to be run, e.g., two levels of QC are required every 8 hours of testing for blood gases. LAP-CAP accepts electronic controls if they are recommended by the manufacturer of the test method. Before they can be used routinely, LAP-CAP requires that the laboratory verify the manufacturer’s QC claims. In addition, external (usually liquid) controls must be run periodically to validate that no change occurred with the testing system. For qualitative tests, LAP-CAP will allow the use of built-in controls, including those with built-in process controls, provided the capability of these have been evaluated thoroughly and the testing site’s director approves their use. If only one “control” is built-in, an additional external control (or “known” patient sample) is required each day of testing. For all tests, LAP-CAP requires an audit trail that ties the patients’ results with the analyst, instrument and QC. In addition, the QC program should show evidence of daily documented review and monthly secondary review by the director or director’s designee.
In the general requirements, CAP states in Laboratory General Checklist (GEN, September 2001) that the overall quality control program for the entire laboratory must be clearly defined and documented. It must include general policies and delegation of responsibilities. The quality control records should be well-organized with a defined system to permit regular review by appropriate supervisory personnel (laboratory director, supervisor or laboratory quality control coordinator).
- (GEN.30000) Does the QC program clearly define goals for monitoring analytic performance, procedures, policies, tolerance limits, corrective action and related information?
Hematology and Coagulation (HEM, October 2001) QC Requirements
- (HEM.20035) Are tolerance limits (numeric and/or non-numeric) fully defined and documented for all hematology and coagulation control procedures?
- (HEM.20050) For numeric data generated by the hematology laboratory, are Gaussian or other quality control statistics (e.g., SD and CV) calculated at least at monthly intervals to define analytic precision?
- (HEM.20070) Does the laboratory have an action protocol when data from precision statistics change significantly from previous data?
- (HEM.20140) Are the results of controls verified for acceptability before reporting results?
Automated/General Chemistry Checklist (AGC, October 2001) QC Requirements
- (AGC.26000) For quantitative tests, are control specimens at more than one concentration (level) used at least daily?
- (AGC.26100) Has a statistically valid target range been established for each lot of control material by repetitive analysis in runs that include previously tested control materials (quantitative tests)?
- (AGC.26150) For qualitative tests, is a positive and negative control included with each run of patient specimens?
- (AGC.26250) Are tolerance limits defined for control procedures?
- (AGC.26275) For numeric QC data, are Gaussian or other quality control statistics (e.g., S.D. and C.V.) calculated at least at monthly intervals to define analytic precision?
- 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.
- Laessig RH, Ehrmeyer SS: New Poor Man’s (Person’) Guide to Meeting the Regulations. R&S Consultants, Madison WI, 2002.
- Accreditation Manual. COLA. Columbia, MD, 2002.
- 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.
- U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA programs: Categorization of Tests and Personnel Modifications. Fed Regist 1995:60:20035-51.
- 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 2000;65:82941-44.
- 2002-2003 Accreditation Manual for Pathology and Clinical laboratory Services. Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Oakbrook Terrace, IL, 2001.
- Checklists. Laboratory Accreditation Program. College of American Pathologists (CAP). Northfield, IL, 2001.
- JCAHO: http://www.jcaho.org
- CAP: http://www.cap.org
- COLA: http://www.cola.org
CLIA information (waived tests, test complexities, federal registers, etc.) :
