42 C.F.R. §§ 493.1261–493.1278

§493.1261. Standard: Bacteriology.

42 C.F.R. § 493.1261

(a)

The laboratory must check the following for positive and negative reactivity using control organisms:

(1)

Each day of use for beta-lactamase methods other than Cefinase TM.

(2)

Each week of use for Gram stains.

(3)

When each batch (prepared in-house), lot number (commercially prepared), and shipment of antisera is prepared or opened, and once every 6 months thereafter.

(b)

For antimicrobial susceptibility tests, the laboratory must check each batch of media and each lot number and shipment of antimicrobial agent(s) before, or concurrent with, initial use, using approved control organisms.

(1)

Each day tests are performed, the laboratory must use the appropriate control organism(s) to check the procedure.

(2)

The laboratory's zone sizes or minimum inhibitory concentration for control organisms must be within established limits before reporting patient results.

(c)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1262. Standard: Mycobacteriology.

42 C.F.R. § 493.1262

(a)

Each day of use, the laboratory must check all reagents or test procedures used for mycobacteria identification with at least one acid-fast organism that produces a positive reaction and an acid-fast organism that produces a negative reaction.

(b)

For antimycobacterial susceptibility tests, the laboratory must check each batch of media and each lot number and shipment of antimycobacterial agent(s) before, or concurrent with, initial use, using an appropriate control organism(s).

(1)

The laboratory must establish limits for acceptable control results.

(2)

Each week tests are performed, the laboratory must use the appropriate control organism(s) to check the procedure.

(3)

The results for the control organism(s) must be within established limits before reporting patient results.

(c)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1263. Standard: Mycology.

42 C.F.R. § 493.1263

(a)

The laboratory must check each batch (prepared in-house), lot number (commercially prepared), and shipment of lactophenol cotton blue when prepared or opened for intended reactivity with a control organism(s).

(b)

For antifungal susceptibility tests, the laboratory must check each batch of media and each lot number and shipment of antifungal agent(s) before, or concurrent with, initial use, using an appropriate control organism(s).

(1)

The laboratory must establish limits for acceptable control results.

(2)

Each day tests are performed, the laboratory must use the appropriate control organism(s) to check the procedure.

(3)

The results for the control organism(s) must be within established limits before reporting patient results.

(c)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1264. Standard: Parasitology.

42 C.F.R. § 493.1264

(a)

The laboratory must have available a reference collection of slides or photographs and, if available, gross specimens for identification of parasites and use these references in the laboratory for appropriate comparison with diagnostic specimens.

(b)

The laboratory must calibrate and use the calibrated ocular micrometer for determining the size of ova and parasites, if size is a critical parameter.

(c)

Each month of use, the laboratory must check permanent stains using a fecal sample control material that will demonstrate staining characteristics.

(d)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1265. Standard: Virology.

42 C.F.R. § 493.1265

(a)

When using cell culture to isolate or identify viruses, the laboratory must simultaneously incubate a cell substrate control or uninoculated cells as a negative control material.

(b)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1267. Standard: Routine chemistry.

42 C.F.R. § 493.1267

For blood gas analyses, the laboratory must perform the following:

(a)

Calibrate or verify calibration according to the manufacturer's specifications and with at least the frequency recommended by the manufacturer.

(b)

Test one sample of control material each 8 hours of testing using a combination of control materials that include both low and high values on each day of testing.

(c)

Test one sample of control material each time specimens are tested unless automated instrumentation internally verifies calibration at least every 30 minutes.

(d)

Document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1269. Standard: Hematology.

42 C.F.R. § 493.1269

(a)

For manual cell counts performed using a hemocytometer—

(1)

One control material must be tested each 8 hours of operation; and

(2)

Patient specimens and control materials must be tested in duplicate.

(b)

For all nonmanual coagulation test systems, the laboratory must include two levels of control material each 8 hours of operation and each time a reagent is changed.

(c)

For manual coagulation tests—

(1)

Each individual performing tests must test two levels of control materials before testing patient samples and each time a reagent is changed; and

(2)

Patient specimens and control materials must be tested in duplicate.

(d)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

§493.1271. Standard: Immunohematology.

42 C.F.R. § 493.1271

(a)

Patient testing.

(1)

The laboratory must perform ABO grouping, D(Rho) typing, unexpected antibody detection, antibody identification, and compatibility testing by following the manufacturer's instructions, if provided, and as applicable, 21 CFR 606.151(a) through (e).

(2)

The laboratory must determine ABO group by concurrently testing unknown red cells with, at a minimum, anti-A and anti-B grouping reagents. For confirmation of ABO group, the unknown serum must be tested with known A1 and B red cells.

(3)

The laboratory must determine the D(Rho) type by testing unknown red cells with anti-D (anti-Rho) blood typing reagent.

(b)

Immunohematological testing and distribution of blood and blood products. Blood and blood product testing and distribution must comply with 21 CFR 606.100(b)(12); 606.160(b)(3)(ii) and (b)(3)(v); 610.40; 640.5(a), (b), (c), and (e); and 640.11(b).

(c)

Blood and blood products storage. Blood and blood products must be stored under appropriate conditions that include an adequate temperature alarm system that is regularly inspected.

(1)

An audible alarm system must monitor proper blood and blood product storage temperature over a 24-hour period.

(2)

Inspections of the alarm system must be documented.

(d)

Retention of samples of transfused blood. According to the laboratory's established procedures, samples of each unit of transfused blood must be retained for further testing in the event of transfusion reactions. The laboratory must promptly dispose of blood not retained for further testing that has passed its expiration date.

(e)

Investigation of transfusion reactions.

(1)

According to its established procedures, the laboratory that performs compatibility testing, or issues blood or blood products, must promptly investigate all transfusion reactions occurring in facilities for which it has investigational responsibility and make recommendations to the medical staff regarding improvements in transfusion procedures.

(2)

The laboratory must document, as applicable, that all necessary remedial actions are taken to prevent recurrences of transfusion reactions and that all policies and procedures are reviewed to assure they are adequate to ensure the safety of individuals being transfused.

(f)

Documentation. The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003]

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003]

§493.1273. Standard: Histopathology.

42 C.F.R. § 493.1273

(a)

As specified in § 493.1256(e)(3), fluorescent and immunohistochemical stains must be checked for positive and negative reactivity each time of use. For all other differential or special stains, a control slide of known reactivity must be stained with each patient slide or group of patient slides. Reaction(s) of the control slide with each special stain must be documented.

(b)

The laboratory must retain stained slides, specimen blocks, and tissue remnants as specified in § 493.1105. The remnants of tissue specimens must be maintained in a manner that ensures proper preservation of the tissue specimens until the portions submitted for microscopic examination have been examined and a diagnosis made by an individual qualified under § 493.1449(b), (f), or (g).

(c)

An individual who has successfully completed a training program in neuromuscular pathology approved by HHS may examine and provide reports for neuromuscular pathology.

(d)

Tissue pathology reports must be signed by an individual qualified as specified in paragraph (b) or, as appropriate, paragraph (c) of this section. If a computer report is generated with an electronic signature, it must be authorized by the individual who performed the examination and made the diagnosis.

(e)

The laboratory must use acceptable terminology of a recognized system of disease nomenclature in reporting results.

(f)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003, as amended at 88 FR 90038, Dec. 28, 2023]

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003, as amended at 88 FR 90038, Dec. 28, 2023]

§493.1274. Standard: Cytology.

42 C.F.R. § 493.1274

(a)

Cytology slide examination site. All cytology slide preparations must be evaluated on the premises of a laboratory certified to conduct testing in the subspecialty of cytology.

(b)

Staining. The laboratory must have available and follow written policies and procedures for each of the following, if applicable:

(1)

All gynecologic slide preparations must be stained using a Papanicolaou or modified Papanicolaou staining method.

(2)

Effective measures to prevent cross-contamination between gynecologic and nongynecologic specimens during the staining process must be used.

(3)

Nongynecologic specimens that have a high potential for cross-contamination must be stained separately from other nongynecologic specimens, and the stains must be filtered or changed following staining.

(c)

Control procedures. The laboratory must establish and follow written policies and procedures for a program designed to detect errors in the performance of cytologic examinations and the reporting of results. The program must include the following:

(1)

A review of slides from at least 10 percent of the gynecologic cases interpreted by individuals qualified under § 493.1469 or § 493.1483, to be negative for epithelial cell abnormalities and other malignant neoplasms (as defined in paragraph (e)(1) of this section).

(i)

The review must be performed by an individual who meets one of the following qualifications:

(A)

A technical supervisor qualified under § 493.1449(b) or (e).

(B)

A cytology general supervisor qualified under § 493.1469.

(C)

A cytotechnologist qualified under § 493.1483 who has the experience specified in § 493.1469(b)(2).

(ii)

Cases must be randomly selected from the total caseload and include negatives and those from patients or groups of patients that are identified as having a higher than average probability of developing cervical cancer based on available patient information.

(iii)

The review of those cases selected must be completed before reporting patient results.

(2)

Laboratory comparison of clinical information, when available, with cytology reports and comparison of all gynecologic cytology reports with a diagnosis of high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma, or other malignant neoplasms with the histopathology report, if available in the laboratory (either on-site or in storage), and determination of the causes of any discrepancies.

(3)

For each patient with a current HSIL, adenocarcinoma, or other malignant neoplasm, laboratory review of all normal or negative gynecologic specimens received within the previous 5 years, if available in the laboratory (either on-site or in storage). If significant discrepancies are found that will affect current patient care, the laboratory must notify the patient's physician and issue an amended report.

(4)

Records of initial examinations and all rescreening results must be documented.

(5)

An annual statistical laboratory evaluation of the number of—

(i)

Cytology cases examined;

(ii)

Specimens processed by specimen type;

(iii)

Patient cases reported by diagnosis (including the number reported as unsatisfactory for diagnostic interpretation);

(iv)

Gynecologic cases with a diagnosis of HSIL, adenocarcinoma, or other malignant neoplasm for which histology results were available for comparison;

(v)

Gynecologic cases where cytology and histology are discrepant; and

(vi)

Gynecologic cases where any rescreen of a normal or negative specimen results in reclassification as low-grade squamous intraepithelial lesion (LSIL), HSIL, adenocarcinoma, or other malignant neoplasms.

(6)

An evaluation of the case reviews of each individual examining slides against the laboratory's overall statistical values, documentation of any discrepancies, including reasons for the deviation and, if appropriate, corrective actions taken.

(d)

Workload limits. The laboratory must establish and follow written policies and procedures that ensure the following:

(1)

The technical supervisor establishes a maximum workload limit for each individual who performs primary screening.

(i)

The workload limit is based on the individual's performance using evaluations of the following—

(A)

Review of 10 percent of the cases interpreted as negative for the conditions defined in paragraph (e)(1) of this section.

(B)

Comparison of the individual's interpretation with the technical supervisor's confirmation of patient smears specified in paragraphs (e)(1) and (e)(3) of this section.

(ii)

Each individual's workload limit is reassessed at least every 6 months and adjusted when necessary.

(2)

The maximum number of slides examined by an individual in each 24-hour period does not exceed 100 slides (one patient specimen per slide; gynecologic, nongynecologic, or both) irrespective of the site or laboratory. This limit represents an absolute maximum number of slides and must not be employed as an individual's performance target. In addition—

(i)

The maximum number of 100 slides is examined in no less than an 8-hour workday;

(ii)

For the purposes of establishing workload limits for individuals examining slides in less than an 8-hour workday (includes full-time employees with duties other than slide examination and part-time employees), a period of 8 hours is used to prorate the number of slides that may be examined. The formula—

(iii)

Nongynecologic slide preparations made using liquid-based slide preparatory techniques that result in cell dispersion over one-half or less of the total available slide may be counted as one-half slide; and

(iv)

Technical supervisors who perform primary screening are not required to include tissue pathology slides and previously examined cytology slides (gynecologic and nongynecologic) in the 100 slide workload limit.

(3)

The laboratory must maintain records of the total number of slides examined by each individual during each 24-hour period and the number of hours spent examining slides in the 24-hour period irrespective of the site or laboratory.

(4)

Records are available to document the workload limit for each individual.

(e)

Slide examination and reporting. The laboratory must establish and follow written policies and procedures that ensure the following:

(1)

A technical supervisor confirms each gynecologic slide preparation interpreted to exhibit reactive or reparative changes or any of the following epithelial cell abnormalities:

(i)

Squamous cell.

(A)

Atypical squamous cells of undetermined significance (ASC-US) or cannot exclude HSIL (ASC-H).

(B)

LSIL-Human papillomavirus (HPV)/mild dysplasia/cervical intraepithelial neoplasia 1 (CIN 1).

(C)

HSIL-moderate and severe dysplasia, carcinoma in situ (CIS)/CIN 2 and CIN 3 or with features suspicious for invasion.

(D)

Squamous cell carcinoma.

(ii)

Glandular cell.

(A)

Atypical cells not otherwise specified (NOS) or specified in comments (endocervical, endometrial, or glandular).

(B)

Atypical cells favor neoplastic (endocervical or glandular).

(C)

Endocervical adenocarcinoma in situ.

(D)

Adenocarcinoma endocervical, adenocarcinoma endometrial, adenocarcinoma extrauterine, and adenocarcinoma NOS.

(iii)

Other malignant neoplasms.

(2)

The report of gynecologic slide preparations with conditions specified in paragraph (e)(1) of this section must be signed to reflect the technical supervisory review or, if a computer report is generated with signature, it must reflect an electronic signature authorized by the technical supervisor who performed the review.

(3)

All nongynecologic preparations are reviewed by a technical supervisor. The report must be signed to reflect technical supervisory review or, if a computer report is generated with signature, it must reflect an electronic signature authorized by the technical supervisor who performed the review.

(4)

Unsatisfactory specimens or slide preparations are identified and reported as unsatisfactory.

(5)

The report contains narrative descriptive nomenclature for all results.

(6)

Corrected reports issued by the laboratory indicate the basis for correction.

(f)

Record and slide retention.

(1)

The laboratory must retain all records and slide preparations as specified in § 493.1105.

(2)

Slides may be loaned to proficiency testing programs in lieu of maintaining them for the required time period, provided the laboratory receives written acknowledgment of the receipt of slides by the proficiency testing program and maintains the acknowledgment to document the loan of these slides.

(3)

Documentation of slides loaned or referred for purposes other than proficiency testing must be maintained.

(4)

All slides must be retrievable upon request.

(g)

Automated and semi-automated screening devices. When performing evaluations using automated and semi-automated screening devices, the laboratory must follow manufacturer's instructions for preanalytic, analytic, and postanalytic phases of testing, as applicable, and meet the applicable requirements of this subpart K.

(h)

Documentation. The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003, as amended at 88 FR 90038, Dec. 28, 2023]

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003, as amended at 88 FR 90038, Dec. 28, 2023]

§493.1276. Standard: Clinical cytogenetics.

42 C.F.R. § 493.1276

(a)

The laboratory must have policies and procedures for ensuring accurate and reliable patient specimen identification during the process of accessioning, cell preparation, photographing or other image reproduction technique, photographic printing, and reporting and storage of results, karyotypes, and photographs.

(b)

The laboratory must have records that document the following:

(1)

The media used, reactions observed, number of cells counted, number of cells karyotyped, number of chromosomes counted for each metaphase spread, and the quality of the banding.

(2)

The resolution is appropriate for the type of tissue or specimen and the type of study required based on the clinical information provided to the laboratory.

(3)

An adequate number of karyotypes are prepared for each patient.

(c)

Determination of sex must be performed by full chromosome analysis.

(d)

The laboratory report must include a summary and interpretation of the observations, number of cells counted and analyzed, and use the International System for Human Cytogenetic Nomenclature.

(e)

The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003]

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

Amendments

[68 FR 3703, Jan. 24, 2003; 68 FR 50724, Aug. 22, 2003]

§493.1278. Standard: Histocompatibility.

42 C.F.R. § 493.1278

(a)

General. The laboratory must meet the following requirements:

(1)

Use a continuous monitoring system and alert system to monitor the storage temperature of specimens (donor and recipient) and reagents and notify laboratory personnel when temperature limits are exceeded.

(2)

Establish and follow written policies and procedures for the storage and retention of specimens based on the specific type of specimen. All specimens must be easily retrievable. The laboratory must have an emergency plan for alternate storage.

(3)

If the laboratory uses immunologic reagents to facilitate or enhance the isolation or identification of lymphocytes or lymphocyte subsets, the efficacy of the methods must be monitored with appropriate quality control procedures.

(4)

Participate in at least one national or regional cell exchange program, if available, or develop an exchange system with another laboratory in order to validate interlaboratory reproducibility.

(b)

Human leukocyte antigen (HLA) typing. The laboratory must do the following:

(1)

Use HLA antigen terminology that conforms to the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System.

(2)

Have available and follow written criteria for determining when antigen and allele typing are required.

(c)

Antibody screening and identification. The laboratory must make a reasonable effort to have available monthly serum specimens for all potential transplant recipients for periodic antibody screening, identification, and crossmatch.

(d)

Crossmatching. For each type of crossmatch that a laboratory performs, the laboratory must do the following, as applicable:

(1)

Establish and follow written policies and procedures for performing a crossmatch.

(2)

Have available and follow written criteria for the following—

(i)

Defining donor and recipient HLA antigens, alleles, and antibodies to be tested;

(ii)

Defining the criteria necessary to assess a recipient's alloantibody status;

(iii)

Assessing recipient antibody presence or absence on an ongoing basis;

(iv)

Typing the donor, to include those HLA antigens to which antibodies have been identified in the potential recipient, as applicable;

(v)

Describing the circumstances in which pre- and post-transplant confirmation testing of donor and recipient specimens is required;

(vi)

Making available all applicable donor and recipient test results to the transplant team;

(vii)

Ensuring immunologic assessments are based on test results obtained from a test report from a CLIA-certified laboratory; and

(viii)

Defining time limits between recipient testing and the performance of a crossmatch.

(3)

The test report must specify the type of crossmatch performed.

(e)

Transplantation. Laboratories performing histocompatibility testing for infusion and transplantation purposes must establish and follow written policies and procedures specifying the histocompatibility testing (that is, HLA typing, antibody screening and identification, and crossmatching) to be performed for each type of cell, tissue, or organ to be infused or transplanted. The laboratory's policies and procedures must include, as applicable—

(1)

Testing protocols that address—

(i)

Transplant type (organ, tissue, cell);

(ii)

Donor (living, deceased, or paired)— and

(iii)

Recipient (high risk vs. unsensitized);

(2)

Type and frequency of testing required to support clinical transplant protocols; and

(3)

Process to obtain a recipient specimen, if possible, for crossmatch that is collected on the day of the transplant and prior to transplantation. If the laboratory is unable to obtain a recipient specimen on the day of the transplant, the laboratory must have a process to document its efforts to obtain the specimen.

(f)

Documentation. The laboratory must document all control procedures performed, as specified in this section.

Notes, amendments, and revision history

Amendments

[88 FR 90038, Dec. 28, 2023]

Source

Source: 68 FR 3703, Jan. 24, 2003, unless otherwise noted.

Authority

Authority: 42 U.S.C. 263a, 1302, 1395x(e), 1395x(s)(3) and (s)(17).

Source

Source: 55 FR 9576, Mar. 14, 1990, unless otherwise noted.

Amendments

[88 FR 90038, Dec. 28, 2023]