On December 26, 2024, The College of American Pathologists’ (CAP) laboratory accreditation program released its latest inspection checklists. Notably, several changes were enacted within the chemistry and toxicology checklist. Three new standards were added, along with several revisions to existing standards.

These changes cover key areas such as hemoglobin A1c (HbA1c) proficiency testing (PT), estimated glomerular filtration rate (eGFR) and low-density lipoprotein (LDL) cholesterol result reporting, mass spectrometry, prenatal screening, human immunodeficiency virus (HIV) primary diagnostic testing, and blood gas analysis. Given the widespread application of CAP standards on clinical activities, herein we review these updated chemistry and toxicology checklist items and provide practical recommendations for compliance.

CAP Standards

HbA1c Proficiency Testing: CHM.12925

Proficiency testing limits are one of the major regulatory updates from the Centers for Medicare and Medicaid Services (CMS) in accordance with the Clinical Laboratory Improvement Amendments (CLIA). Previously unregulated, HbA1c is now included as a regulated analyte with PT acceptance criteria set at ±8% from target value.

Previous criteria varied among PT providers with ±20% set by American Proficiency Institute (API), whereas CAP has been more stringent with ±6%. Further, National Glycohemoglobin Standardization Program (NGSP) certification requires assay manufacturers to meet the target goal of ±5% of the expected mean in at least 36 out of 40 samples. To align with the CLIA final rule, CAP will provide dual grading at ±8% (CLIA requirement) and ±6% (CAP requirement) in the participant summary report this year. This creates a unique scenario when a survey specimen has a bias from the target value of greater than ±6%, but less than ±8% wherein the CAP evaluation report will display “acceptable” with ±8% criteria and “unacceptable” with ±6% criteria. For CAP-accredited labs, this scenario will still require corrective action due to exceeding the ±6% criterion.

For laboratories to comply with this standard, evidence showing accuracy-based PT evaluated against the ±6% target is required. While this requirement may not be an issue for labs already subscribed to CAP PT, we recommend that those using API (or alternate material, prospectively) evaluate their test performance as a cautionary step to ensure they will meet the stricter limits. Additionally, laboratories utilizing non-CAP accuracy-based PT likely will need to manually calculate ±6% limits and document self-grading.

A similar CAP standard also is included in the point-of-care testing (POCT) checklist (POC.03325). Certain manufacturers of CLIA-waived HbA1c POCTs have historically used the allowable total error of ±10% to verify test performance. This standard will now urge manufacturers to align their performance specifications with the ±8% target.

eGFR and LDL Cholesterol Result Reporting: CHM.15225

Among several calculated results reported by clinical laboratories, eGFR and LDL cholesterol are two of the most common and are especially important, as they often directly guide clinical decision making. CAP now requires laboratories to explicitly report the equation used for calculating these results. Indeed, in the last 5-10 years, several modifications and new equations have been adopted by laboratories. There are (arguably) five common eGFR equations (MDRD, 2021 CKD-EPI creatinine, 2021 CKD-EPI CysC-creatinine, Bedsize Schwartz, and Schwartz CysC) and three LDL cholesterol equations (Friedewald, Martin-Hopkins, and Sampson). Of these, our observations suggest the 2021 CKD-EPI creatinine and Friedewald equations are most commonly used; however, this varies by laboratory. Providing the specific equation allows the provider to properly interpret the result within the limitations of said equation and facilitates the comparability of results across laboratories.

Evidence of compliance with this standard may include listing equations in patient reports or a test reference guide. Alternatively, labs may incorporate this information into the test name. We recommend inclusion of the equation as a comment in the patient report, as well as in the test catalog, to aid in clinician access pre- and post-ordering process.

In addition to the name of the equation and formulae, citing the original reference in test reports may be beneficial, particularly for non-renal providers. This standard applies also to POCTs and is addressed in POC.04425. Once laboratories implement this standard, it may be worthwhile to communicate this change to clinicians.

Mass Spectrometry: CHM.18640, CHM.20600

Clinical mass spectrometry is rapidly evolving, driven by advancements in automation, multiplexing, and data analytics, among many other innovations. In parallel, the related regulatory standards are evolving, as evidenced by the revision of two standards. The first revision—to CHM.18640—now requires laboratories to verify the performance of data analysis tools, annually. This standard applies to tools within a middleware system that performs functions such as auto-peak integration, ion mass ratio calculations, and carryover risk assessment, but also may apply to the manufacturer-supplied mass spectrometer instrument software in some cases. This checklist item likely will apply mostly to third-party software, often referred to as a “black box” that easily can be overlooked and/or remain undetected as a source of error. The intent of this requirement is to ensure that the data analysis tools used for compound identification and quantification are working appropriately and have not been impacted by end-user or software/middleware manufacturer modifications. Demonstration of compliance will be situationally based on the individual tools and how they are utilized. However, a version control strategy is now required for all custom data analysis tools. One method by which labs may choose to comply is to perform a method comparison with an alternate method using specimens that challenge the lower limit of quantification and clinical decision points. In addition to records showing compliance, a standard operating procedure (SOP) documenting the following is required:

1. Purpose of each tool
2. Functionality
3. Interaction with other programs
4. Change management/modification specifications
5. Troubleshooting procedures

The second revision—to CHM.20600—is related to monitoring interference caused by oxides and doubly-charged species in inductively coupled plasma mass spectrometry (ICP-MS). This revision is unlikely to change current practice, as it simply eliminates redundant verbiage from the previous version.

Prenatal Screening: CHM.31150, CHM.31900, CHM.31950, CHM.31960, CHM.32300, and CHM.32400

Several updates appear in the section on prenatal screening for neural tube defects and aneuploidies, where CAP has consolidated 10 separate standards into a single streamlined standard, along with other revisions. The new consolidated standard grants laboratories slightly greater autonomy in defining the essential elements required for prenatal screening risk calculations. CAP’s expected elements include gestational age, in vitro fertilization method, initial or repeat testing status, maternal age, maternal race or subpopulation, maternal weight, diabetic medications, number of fetuses, and smoking status. These elements are essentially the same as the previous checklist elements; however, laboratories can now choose to exclude any of these elements with proper documentation of the rationale.

Notably, language regarding specific races (eg, “Black”) and ethnic groups (eg, “Hispanic Asian,” “Native American”) has been removed. This change reflects the ongoing debate over the inclusion of maternal race in risk calculations. Interestingly, the study cited in the CAP checklist does not support a race-agnostic approach, as it has been associated with higher screen-positive rates, leading to disproportionate follow-up care for individuals of a particular race. Another notable revision is the generalization of “smoking” status, replacing the previous version’s specific reference to cigarette use.

Additional tweaks and changes to these standards on prenatal screening include a semantic change in terminology of median value “reverification” to “review.” Certainly, CAP recommends periodic review of median values as defined in the laboratory SOPs, and evidence of compliance can include records of median value review or calculation at specified time intervals or test volumes.

Another change is noted for nuchal translucency quality, which is the ultrasound-guided measurement of space between fetal skin and soft tissue covering the cervical spine. This parameter usually is a component of combined and sequential prenatal screening panels offered in the first trimester. CAP’s revised standard omits the requirement for quality assessment based on sonographer credentials, performance evaluation, etc. Instead, a risk-based approach to determine the accuracy of nuchal translucency results is recommended. Labs will have to redefine their quality assurance plan to comply with this standard.

Lastly, prenatal screen requisitions now must include all elements that were previously required only in the prenatal screen report, while these elements must still remain in the report. Specific clinical variables to consider for adjustment of multiples of median was omitted.

Amniotic Fluid Alpha-Fetoprotein: CHM.32800, CHM.32900

Similar to the prenatal screening section, a terminology change from “reverification” to “review” is noted for amniotic fluid alpha-fetoprotein median values. Comment on differential concentrations among specific racial groups is omitted, reflecting a broader effort to step back on the utilization of race correction factors.

HIV Primary Diagnostic Testing: CHM.33790

Historically, CAP has not mandated that labs follow public health recommendations and guidelines for HIV primary diagnostic testing for therapeutic product donors or individuals undergoing HIV monitoring (ie, viral load, CD4 counts). The current checklist reverses this approach by removing the exemption for these two situations. This checklist item also should serve as a reminder for labs to verify whether their assay is FDA cleared for use in screening therapeutic blood or plasma donors, especially in light of the upcoming implementation of the laboratory-developed tests final rule. To comply, labs can explicitly state their secondary testing processes in their SOP and assign as a mandatory reading, including for key stakeholders from their institution’s transfusion medicine practice.

Blood Gas Analysis: CHM.33900

The CAP standard on the requirement for collateral circulation verification with radial artery sampling in blood gas analysis has undergone a minor wording change from “as applicable” to “if clinically indicated.” Specific requirements to define the preferred method and situations (ie, a definition of when it is clinically indicated), and recording of sites have been removed, although they are still inferred through the requirement of a written procedure and evidence of compliance. This modification is not likely to alter practices for most laboratories.

Conclusion

Overall, these altered standards capture the current and ongoing regulatory changes and are expected to have a minimal impact on current laboratory operations. The most notable update is the accessibility of calculated eGFR and LDL cholesterol equations for clinicians, which may require coordination among cross-functional teams, including laboratory staff, information technology representatives, and clinician groups. For a more in-depth understanding of how these updates apply to your practice, we recommend reaching out to CAP directly for further clarification at accred@cap.org.

References

1. College of American Pathologists (CAP). Chemistry and Toxicology Checklist. 2024. www.cap.org/laboratory-improvement/accreditation/accreditation-checklists
2. Pierre CC, Greene DN, Delaney S, Lockwood CM, Peck Palmer OM. Reconsidering the use of race adjustments in maternal serum screening. Am J Obstet Gynecol. 2023.

Anil Chokkalla, PhD, NRCC, is the technical director of chemistry and point-of-care testing at Sanford Laboratories in Fargo, North Dakota. He also is a CLIA high-complexity laboratory director for Sanford Children’s Southwest and Sanford Southpointe Laboratories. In addition, Anil holds academic appointment as a clinical assistant professor of pathology at the University of North Dakota, School of Medicine. His clinical research work focuses on quality improvement, diagnostic stewardship, and evidence-based practice.

Christopher Koch, PhD, DABCC, is the medical director of the Sanford Laboratories Reference Labs in Sioux Falls and Rapid City, South Dakota. He holds academic appointments as a clinical assistant professor of pathology at the University of South Dakota Sanford School of Medicine, and as a clinical investigator at Sanford Research, Sanford Health. Chris is currently the Chair for the Midwest Section of the Association for Diagnostics and Laboratory Medicine (ADLM).

For Further Reading

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