CHAPTER 8

REGULATED ANALYTES


8-1. Introduction

Paragraphs §493.911 through §493.959 of 42 CFR 493 explain the content of approved proficiency test programs. For a further explanation the reader is directed to either the Code of Federal Regulations, or the Federal Register, 28 February 1992, pages 7152 through 7162 (paragraphs §493.911 through §493.959). The following section summarizes the stated paragraphs to provide a concise list of regulated analytes. The reference paragraph is noted for each subspecialty.

8-2. Bacteriology (§493.911)

The annual program must include samples that contain organisms that are representative of the six major groups of bacteria: anaerobes, Enterobacteriaceae, gram-positive bacilli, gram-positive cocci, gram-negative cocci,miscellaneous gram-negative bacteria. Specific organisms may vary from year to year. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal
intervals per year. Examples of the types of organisms that might be included over time are:

a. Anaerobes:


(1) Bacteroides fragilis group
(2) Clostridium perfringens
(3) Peptostreptococcus anaerobius


b. Enterobacteriaceae:


(1) Citrobacter freundii
(2) Enterobacter aerogenes
(3) Escherichia coli
(4) Klebsiella pneumoniae
(5) Proteus mirabilis
(6) Salmonella typhimurium
(7) Serratia marcescens
(8) Shigella sonnei
(9) Yersinia enterocolitica


c. Gram-positive bacilli:


(1) Listeria monocytogenes
(2) Cornebacterium species CDC group JK


d. Gram-positive cocci:


(1) Staphylococcus aureus
(2) Streptococcus Group A
(3) Streptococcus Group B
(4) Streptococcus Group D (S. Bovis and enterococcus)
(5) Streptococcus Group pneumoniae


e. Gram-negative cocci:


(1) Branhamella catarrhalis
(2) Neisseria gonorrhoeae
(3) Neisseria meningitidis


f. Miscellaneous Gram-negative bacteria:


(1) Campylobacter jejuni
(2) Haemophilis influenza, Type B
(3) Pseudomonas aeruginosa.


A laboratory's performance will be evaluated for only those antibiotics for which service is offered. Evaluation of laboratory responses for particular samples is dependent upon the extent of services offered by the laboratory for this subspecialty. Bacteriology services are classified into five types, from laboratories that perform only Gram stains and/or primary inoculations to full service laboratories that perform isolation and identification of anaerobic bacteria. For further information refer to 57 FR 7152.


8-3. Mycobacteriology (§493.913)

The annual program must include samples that contain organisms that are representative of the five major groups(complexes) of mycobacteria encountered in human specimens. Specific organisms may vary from year to year. The program must provide a minimum of five samples per testing event. There must be at least two testing events at approximately equal intervals per year. Examples of the types of organisms that might be included over time are:


a. TB


(1) Mycobacterium tuberculosis
(2) Mycobacterium bovis


b. Group I

Mycobacterium kansasii


c. Group II


Mycobacterium szulgai


d. Group III


(1) Mycobacterium avium-intracellulare
(2) Mycobacterium terrae


e. Group IV


Mycobacterium fortuitum


Evaluation of laboratory responses for particular samples is dependent upon the extent of services offered by the laboratory for this subspecialty. Mycobacteriology services are classified into five types, from laboratories that perform only interpretation of Acid-fast Stains to full service laboratories that perform isolation, identification and antimycobacterial susceptibility testing of mycobacteria. For further information refer to 57 FR 7154.

8-4. Mycology (§493.915)

The annual program must include samples that contain organisms that are representative of the five major groups of fungi: Yeast or yeast-like fungi, dimorphic fungi, dematiaceous fungi, dermatophytes, ans saprophytes, including opportunistic fungi. Specific organisms may vary from year to year. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Examples of the types of organisms that might be included over time are:

a. Candida albicans
b. Candida (other species)
c. Cryptococcus neoformans
d. Sporothrix schenckii
e. Exophiala jeanselmei
f. Fonsecaea pedrosoi
g. Microsporum sp.
f. Acremonium sp.
g. Trichophvton sp.
h. Aspergillas fumigatus
i. Nocardia sp.
j. Blastomyces dermatitidis
k. Zygomycetes sp.

Evaluation of laboratory responses for particular samples is dependent upon the extent of services offered by the laboratory for this subspecialty. Mycology services are classified into four types, from laboratories that isolate yeasts or dermatophytes to the genus level to full service laboratories that perform isolation and identification of all mycology to the species level. For further information refer to 57 FR 7154.

8-5. Parasitology (§493.917)

The annual program must include samples that contain parasites that are commonly encountered in the United States as well as those recently introduced into the United States. Other important emerging pathogens (as determined by HHS) and parasites commonly occurring in patient specimens will be included periodically in the program. Specific organisms may vary from year to year. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Examples of the types of organisms that might be included over time are:

a. Enterobius vermicularis
b. Entamoeba histolytica
c. Entomoeba coli
d. Giardia lamblia
e. Endolimax nana
f. Dientamoeba fragilis
g. Iodamoeba butschli
h. Chilomastix mesnili
I. Hookworm
j. Ascaris lumbricoides
k. Strongyloides stercoralis
l. Trichuris trichiura
m. Diphyllobothrium latum
n. Cryptosporidium sp.
o. Plasmodium falciparum

Evaluation of laboratory responses for particular samples is dependent upon the extent of services offered by the laboratory for this subspecialty. Parasitology services are classified into two types, from laboratories that determine the presence or absence of parasites by direct observation (wet mount or pinworm preps) to laboratories that perform identification of parasites using concentrations and permanent stains. For further information refer to 57 FR 7155.

8-6. Virology (§493.919)

The annual program must include viral species that are the more commonly identified viruses. Specific organisms may vary from year to year. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. No examples are provided. Evaluation of laboratory responses for particular samples is dependent upon the extent of services offered by the laboratory for this subspecialty. Virology services are classified into two types, from laboratories that directly detect viral antigens or structures to full service laboratories that perform isolation and identification of viruses and use direct antigen techniques. For further information refer to 57 FR 7156.

8-7. Diagnostic Immunology (§493.921)

Proficiency testing programs for this specialty are found under syphilis serology (§493.923) and diagnostic immunology (§493.927).

a. Syphilis Serology (§493.923) The annual program must include samples that cover the full range of reactivity from highly reactive to non-reactive. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. No examples are provided.

b. Diagnostic Immunology (§493.927) The annual program must include samples that cover the full range of reactivity from highly reactive to non-reactive. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Analytes or tests for which laboratory performance is to be evaluated include:

Analyte or test
Acceptable Performance

Alpha-1 antitrypsin
Target value +/- 3 SD


Alpha-fetoprotein (tumor marker)
Target value +/- 3 SD


Antinuclear antibody
Target value +/- 2 dilutions or + or -


Antistreptolysin O, quantitative
Target value +/- 2 dilutions or + or -


Anti-human immunodeficiency virus (HIV)
Target value +/- Reactive or nonreactive


Complement C3
Target value +/- 3 SD


Complement C4
Target value +/- 3 SD


(HbsAg, anti-HBc, HbeAg) Hepatitis markers
Target value +/- Reactive (positive) or nonreactive (negative)


IgA
Target value +/- 3 SD


IgG
Target value +/- 25%


IgE
Target value +/- 3 SD


IgM
Target value +/- 3 SD


Infectious mononucleosis
Target value +/- 2 dilutions or + or -


Rheumatoid factor
Target value +/- 2 dilutions or + or -


Rubella
Target value +/- 2 dilutions or + or - or immune or nonimmune.


8-8. Chemistry (§493.929)

The subspecialties under the specialty of chemistry for which a proficiency testing program may offer proficiency testing are routine chemistry, endocrinology, and toxicology. Specific criteria for these subspecialties are listed in §493.931 through §493.939.

a. Routine Chemistry (§493.931) The annual program must include samples that cover the clinically relevant range of values that would be expected in patient specimens. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Analytes or tests for which laboratory performance is to be evaluated include:

Analyte or test
Acceptable performance

Alanine aminotransferase (ALT/SGPT)
Target value +/- 20%


Albumin
Target value +/- 10%


Alkaline Phosphatase
Target value +/- 30%


Amylase
Target value +/- 30%


Aspartate aminotransferase (AST/SGOT)
Target value +/- 20%


Bilirubin, total
Target value +/- 20% or 0.4mg/dL (greater)


Blood gas pO2
Target value +/- 3 SD


pCO2
Target value +/- 8% or 5mm Hg (greater)


pH
Target value +/- 0.04


Calcium
Target value +/- 1.0 mg/dL


Chloride
Target value +/- 5%


Cholesterol, total
Target value +/- 10%


Cholesterol, high density lipoprotein
Target value +/- 30%


Creatine kinase
Target value +/- 30%


Creatine kinase isoenzymes
Target value +/- 3 SD or MB elevated (presence or absence)


Creatinine
Target value +/- 15% or 0.3mg/dL (greater)


Glucose (excluding glucose performed on monitoring devices cleared by FDA for home use)
Target value +/- 10% or 6 mg/dL (greater)


Iron, total
Target value +/- 20%


Lactate dehydrogenase (LDH)
Target value +/- 20%


Lactate dehydrogenase isoenzymes
Target value +/- 30% or LDH1/LDH2 (+ or -)


Magnesium
Target value +/- 25%


Potassium
Target value +/- 0.5 mmol/L


Sodium
Target value +/- 4 mmol/L


Total protein
Target value +/- 10%


Triglycerides
Target value +/- 25%


Urea nitrogen
Target value +/- 9% or 2 mg/dL (greater)


Uric Acid
Target value +/- 17%


b. Endocrinology (§493.933) The annual program must include samples that cover the clinically relevant range of values that would be expected in patient specimens. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Analytes or tests for which laboratory performance is to be evaluated include:

Analyte or test
Acceptable Performance

Cortisol
Target value +/- 25%


Free thyroxine
Target value +/- 3 SD


Human chorionic gonadotropin
Target value +/- 3 SD or + or -


T3 uptake
Target value +/- 3 SD


Triiodothyronine
Target value +/- 3 SD


Thyroid-stimulating hormone
Target value +/- 3 SD


Thyroxine
Target value +/- 20% or 1mcg/dL (greater)


8-9. Toxicology (§493.937)

The annual program must include samples that cover the clinically relevant range of values that would be expected in specimens of patients on drug therapy and that cover the level of clinical significance for the particular drug. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Analytes or tests for which laboratory performance is to be evaluated include:

Analyte or test
Acceptable performance

Alcohol, blood
Target value +/- 25%


Blood lead
Target value +/- 10% or 4 mcg/dL (greater)


Carbamazepine
Target value +/- 25%


Digoxin
Target value +/- 20% or 0.2ng/mL (greater)


Ethosuximide
Target value +/- 20%


Gentamicin
Target value +/- 25%


Lithium
Target value +/- 20% or 0.3mmol/L (greater)


Phenobarbital
Target value +/- 20%


Phenytoin
Target value +/- 25%


Primidone
Target value +/- 25%


Procanimide (and metabolite)
Target value +/- 25%


Quinidine
Target value +/- 25%


Tobramycin
Target value +/- 25%


Theophylline
Target value +/- 25%


Valproic acid
Target value +/- 25%


8-10. Hematology (including routine hematology and coagulation) (§493.941)

The annual program must include samples that cover the full range of values that would be expected in patient specimens. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Analytes or tests for which laboratory performance is to be evaluated include:

Analyte or test
Acceptable performance

Cell identification
90% or greater consensus on identification


White blood cell differential
Target +/- 3 SD based on the percentage of different types of white blood cells in the samples


Erythrocyte count
Target +/- 6%


Hematocrit (excluding spun hematocrits)
Target +/- 6%


Hemoglobin
Target +/- 7%


Leukocyte count
Target +/- 15%


Platelet count
Target +/- 25%


Fibrinogen
Target +/- 20%


Partial thromboplastin time
Target +/- 15%


Prothrombin time
Target +/- 15%


8-11. Cytology; gynecologic examinations (§493.945)

The annual program must provide test sets composed of 10 and 20 glass slides. Each test set must include at least one slide representative of each of the following response categories:

a. Unsatisfactory for diagnosis
b. Normal or benign changes
c. Low grade squamous intraepithelial lesion
d. High grade squamous intraepithelial lesion.

The program must provide announced and unannounced on-site testing for each individual at least once per year and must provide an initial retesting event for each individual within 45 days after notification of test failure and subsequent retesting events within 45 days after completion of remedial action. The scoring system rewards or penalizes participants in proportion to the distance of their answers from the correct response or target diagnosis and the penalty or reward is weighted in proportion to the severity of the lesion.

8-12. Immunohematology (§493.959)

The annual program must include samples that cover the full range of interpretation that would be expected in patient specimens. The program must provide a minimum of five samples per testing event. There must be at least three testing events at approximately equal intervals per year. Analytes or tests for which laboratory performance is to be evaluated include:

Analyte or test
Acceptable performance

ABO group
100% accuracy


D (Rho) typing
100% accuracy


Unexpected antibody detection
80% accuracy


Compatibility testing
100% accuracy


Antibody identification
80% accuracy

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