§809.10. Labeling for in vitro diagnostic products. — Inbound Citations

(b) A product intended for use in the diagnosis of disease and which is an in vitro diagnostic product as defined in paragraph (a) of this section shall be deemed to be in compliance with the requirements of this section and section 502(f)(1) of the act if it meets the requirements of § 809.10 of this chapter.

(a) In addition to the applicable labeling requirements of §§ 610.62 through 610.65 and § 809.10 of this chapter, and in lieu of the requirements in §§ 610.60 and 610.61 of this chapter, the following requirements shall be met:

(i) The final container label of all Blood Grouping Reagents shall be completely white, except that all or a portion of the final container label of the following Blood Grouping Reagents may be color coded with the specified color which shall be a visual match to a specific color sample designated by the Director, Center for Biologics Evaluation and Research. Printing on all final container labels shall be in solid black. A logo or company name may be placed on the final container label; however, the logo or company name shall be located along the bottom or end of the label, outside the main panel.

(ii) The proper name “Blood Grouping Reagent” need not appear on the final container label provided the final container is distributed in a package and the package label bears the proper name. The final container label shall bear the following information:

(I) If a dried product, to remind users to record the reconstitution date on the label, the statement “RECONSTITUTION DATE ___. EXPIRES 1 YEAR AFTER RECONSTITUTION DATE.”

(iii) The type size for the specificity of the antibody designation on the labels of a final container with a capacity of less than 5 milliliters shall be not less than 12 point. The type size for the specificity of the antibody designations on the label of a container with a capacity of 5 milliliters or more shall be not less than 18 point.

(iv) When the label has been affixed to the final container, a sufficient area of the container shall remain uncovered for its full length or no less than 5 millimeters of the lower circumference to permit inspection of the contents. The label on a final product container for antibodies Anti-c, Anti-k, or Anti-s shall display a bar immediately over the specificity letter used in the name, i.e., Anti-c , Anti-k , or Anti-s .

(2) The following information shall appear either on the package label or on the final container label if it is visible within the package.

(viii) Volume or equivalent volume for dried products when reconstituted, and precautions for adequate mixing when reconstituting.

(xii) If a dried product, a statement indicating the period within which the product may be used after reconstitution.

(xiii) “FOR IN VITRO DIAGNOSTIC USE.”

(xiv) “MEETS FDA POTENCY REQUIREMENTS.”

(xv) If human blood was used in manufacturing the product, the statement: “CAUTION: ALL BLOOD PRODUCTS SHOULD BE TREATED AS POTENTIALLY INFECTIOUS. SOURCE MATERIAL FROM WHICH THIS PRODUCT WAS DERIVED WAS FOUND NEGATIVE WHEN TESTED IN ACCORDANCE WITH CURRENT FDA REQUIRED TESTS. NO KNOWN TEST METHODS CAN OFFER ASSURANCE THAT PRODUCTS DERIVED FROM HUMAN BLOOD WILL NOT TRANSMIT INFECTIOUS AGENTS.”

(xvi) A statement of an observable indication of an alteration of the product, e.g., turbidity, color change, precipitate, that may indicate possible deterioration of the product.

(3) Each final container of Blood Grouping Reagent shall be accompanied by a package insert meeting the requirements of § 809.10. If two or more final containers requiring identical package inserts are placed in a single package, only one package insert per package is required.

(a) In addition to the items required by § 809.10 of this chapter and other applicable labeling provisions of this chapter, the following information shall be included in the labeling:

(i) A logo or company name may be placed on the final container label, however, the logo or company name shall be located along the bottom or end of the label, outside of the main panel.

(ii) If washing the cells is required by the manufacturer, the container label shall include appropriate instructions; if the cells should not be washed before use, e.g., if washing will adversely affect the product, the package insert shall explain.

(2) The container label of Group O cells shall state:

“FOR USE IN DETECTION OF UNEXPECTED ANTIBODIES” or “FOR USE IN IDENTIFICATION OF UNEXPECTED ANTIBODIES” or “NOT FOR USE IN DETECTION OR IDENTIFICATION OF UNEXPECTED ANTIBODIES”.

(3) Except as provided in this section, the container and package labels shall state the percentage of red blood cells in the suspension either as a discrete figure with a variance of more than [±] 1 percentage unit or as a range the extremes of which differ by no more than 2 percentage units. If the stated red blood cell concentration is less than 2 percent, the variance shall be no more than [±] 0.5 percentage unit.

(4) The words “pooled cells” shall appear on the container and package labels of products prepared from pooled cells. The package label or package insert shall state that pooled cells are not recommended for pre-transfusion tests, done in lieu of a major crossmatch, to detect unexpected antibodies in patients' samples.

(5) The package insert of a pooled product intended for detection of unexpected antibodies shall identify the number of donors contributing to the pool. Products designed exclusively for ABO Serum Grouping and umbilical cord cells need not identify the number of donors in the pool.

(6) When the product is a multicontainer product, e.g., a cell panel, the container label and package label shall be assigned the same identifying lot number, and shall also bear a number or symbol to distinguish one container from another. Such number or symbol shall also appear on the antigenic constitution matrix.

(7) The package label or package insert shall state the blood group antigens that have been tested for and found present or absent on the cells of each donor, or refer to such information in an accompanying antigenic constitution matrix. Cells for ABO Serum Grouping are exempt from this requirement. The package insert or antigen constitution matrix shall list each of the antigens tested with only one source of antibody.

(8) The package label or package insert shall bear the cautionary statement: “The reactivity of the product may decrease during the dating period.”

(9) The package insert of a product intended for the detection or identification of unexpected antibodies shall note that the rate at which antigen reactivity (e.g., agglutinability) is lost is partially dependent upon individual donor characteristics that are neither controlled nor predicted by the manufacturer.

(10) The package insert shall provide adequate directions for use.

(11) The package insert shall bear the statement:

“CAUTION: ALL BLOOD PRODUCTS SHOULD BE TREATED AS POTENTIALLY INFECTIOUS. SOURCE MATERIAL FROM WHICH THIS PRODUCT WAS DERIVED WAS FOUND NEGATIVE WHEN TESTED IN ACCORDANCE WITH CURRENT FDA REQUIRED TESTS. NO KNOWN TEST METHODS CAN OFFER ASSURANCE THAT PRODUCTS DERIVED FROM HUMAN BLOOD WILL NOT TRANSMIT INFECTIOUS AGENTS.”

(12) The package insert or the antigenic constitution matrix for each lot of product shall specify the date of manufacture or the length of the dating period.

(13) Manufacturers shall identify with a permanent donor code in the product labeling each donor of peripheral blood used for detection or identification of unexpected antibodies.

(a) In addition to the requirements of §§ 610.60, 610.61, and 809.10 of this chapter, the labeling shall bear the following:

(1) The “d and y” antigen subtype and the source of the product to follow immediately the proper name on both the final container label and the package label. If the product is intended to identify antibodies to the “r and w” antigen subtype, the antigen subtype designation shall include the “r and w” antigen subtype.

(2) The name of the test method(s) recommended for use of the product on the package label and on the final container label, when capable of bearing a full label (see § 610.60(a) of this chapter).

(3) A warning on the package label and on the final container label stating that the product is capable of transmitting hepatitis and should be handled accordingly.

(4) The package shall include a package insert providing:

(i) Detailed instructions for use,

(ii) An adequate description of all recommended test methods, and

(iii) Warnings as to possible hazards, including hepatitis transmitted in handling the product and any ancillary reagents and materials accompanying the product.

(a) In addition to the applicable labeling requirements of §§ 610.62 through 610.65 and § 809.10 of this chapter, and in lieu of the requirements in §§ 610.60 and 610.61 of this chapter, the following requirements shall be met:

(i) The main panel of the final container label of all Anti-IgG, -C3d (polyspecific) reagents shall be white or colorless and printing shall be solid dark contrasting lettering. The main panel of the final container label of all other Anti-Human Globulin reagents shall be black with solid white lettering. A logo or company name may be placed on the final container label; however, the logo or company name shall be located along the bottom or end of the label, outside of the main panel.

(ii) The proper name “Anti-Human Globulin” need not appear on the final container label provided the final container is distributed in a package and the package label bears the proper name. The final container label shall bear the following information:

(A) Anti-Human Globulin may contain one or more antibodies to either immunoglobulins or complement components but the name of each significant antibody must appear on the final container label (e.g., anti-C3b, -C3d, -C4d). The final container labels of polyspecific Anti-Human Globulin are not required to identify antibody specificities other than anti-IgG and anti-C3d but the reactivity of the Anti-Human Globulin shall be accurately described in the package insert.

(H) For example, “DOES NOT CONTAIN ANTIBODIES TO IMMUNOGLOBULINS” or “DOES NOT CONTAIN ANTIBODIES TO COMPLEMENT COMPONENTS.”

(I) If the final container is not enclosed in a package, all items required for a package label shall appear on the container label.

(iii) The type size for the designation of the specific antibody on the label of a final container shall be not less than 12 point, unless otherwise approved by the Director, Center for Biologics Evaluation and Research. The prefix anti- and other parts of the name such as polyspecific may appear in smaller type.

(iv) When the label has been affixed to the final container, a sufficient area of the container shall remain uncovered for its full length or for no less than 5 millimeters of the lower circumference to permit inspection of the contents.

(2) The following items shall appear either on the package label or on the final container label if see-through packaging is used:

(i) Proper name of the product, and the name of the antibody or antibodies as listed in paragraph (a)(4) of this section.

(x) “For In Vitro Diagnostic Use.”

(xi) “Meets FDA Potency Requirements.”

(xii) A statement of an observable indication of an alteration of the product, e.g., turbidity, color change, precipitate, that may indicate possible deterioration of the product.

(3) Each final container of Anti-Human Globulin shall be accompanied by a package insert meeting the requirements of § 809.10 of this chapter. If two or more final containers requiring identical package inserts are placed in a single package, only one package insert per package is required.

(4) Anti-Human Globulin preparations may contain one or more of the antibody specificities listed in this paragraph as described in paragraph (a)(1)(ii)(A) of this section.

A product intended for use in the diagnosis of disease and which is an in vitro diagnostic product as defined in § 809.3(a) of this chapter shall be deemed to be in compliance with the requirements of this part and section 502(f)(1) of the Federal Food, Drug, and Cosmetic Act if it meets the requirements of subpart B of this part and the requirements of § 809.10 of this chapter.

(2) The labeling required under § 809.10 of this chapter must include the following:

(i) A statement in the indications for use that the device is intended to be used for the determination of menopausal status only in conjunction with other clinical and laboratory findings prior to any diagnostic or treatment decisions.

(ii) A limiting statement that the device is intended to be used for the determination of menopausal status only in conjunction with other clinical and laboratory findings prior to any diagnostic or treatment decisions.

(iii) A limiting statement appropriately describing the risks of false test results and that test results should not be relied upon in clinical decision making (e.g., to discontinue contraceptive use and/or to evaluate patients for the presence of endometrial cancer) without other clinical and laboratory findings.

(2) The labeling required under § 809.10 of this chapter must include a limiting statement indicating that the results should be used only as an aid in the nutritional management of infants and not as the sole basis for making nutrition decisions.

(1) Labeling in conformance with 21 CFR 809.10 and

(2) The labeling required under § 809.10 of this chapter must include a limiting statement conveying that the assay should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures and that results from the assay alone should not be used in making treatment decisions.

(2) The labeling required under § 809.10 of this chapter must include:

(i) Clear information, written in language appropriate for the intended user, that describes instructions for how test results should be interpreted. These instructions must be supported by valid scientific evidence and include:

(A) Appropriate explanation of the claimed pharmacogenetic associations for all variants included in the test, any relevant variants not included in the test (e.g., that may contribute to false negative results), and specific considerations by ethnicity, and

(B) Appropriate explanation of non-genetic and non-tested genetic factors that may impact interpretation of the test results;

(ii) Detailed descriptions of analytical performance including, as applicable, precision, reproducibility, accuracy, limits of detection, and interferences as specified in paragraph (b)(1)(i) of this section, in language appropriate for the intended user;

(iii) A warning statement that the patient should not use the test results to stop or change any medication, and that medications should always be taken as prescribed by a healthcare professional;

(iv) A limiting statement explaining that this test is not intended to inform the patient about their current state of health, including whether the patient should or should not take a medication, or how much of a medication the patient should take, as appropriate;

(v) A warning statement that the test does not diagnose any health conditions and is not a substitute for visits to a doctor or other healthcare professional; and

(vi) A prominent and conspicuous limiting statement that the test provides only a preliminary test result that needs to be confirmed using an independent pharmacogenetic test without such a limitation prior to making any medical decisions. Alternatively, appropriate design verification and validation activities, including the generation of robust analytical data demonstrating appropriate analytical accuracy and reliability of test results for each genetic variant included in the test report, must be performed that demonstrate that the test can be used to make well-informed clinical decisions.

(2) The device's labeling required under § 809.10 of this chapter must include a warning statement that explains: “This assay should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures.”

(3) Your 21 CFR 809.10 labeling must include the following:

(i) If indicated for use as a screening test to identify preliminary results for further confirmation, the intended use must state “This assay provides only a preliminary analytical result. A more specific alternative chemical confirmatory method (e.g., gas or liquid chromatography and mass spectrometry) must be used to obtain a confirmed analytical result. Clinical consideration and professional judgment must be exercised with any drug of abuse test, particularly when the preliminary test result is positive.”

(ii) “This test should not be used to monitor therapeutic drug concentrations or to inform dosing adjustment decisions.”

(3) Your § 809.10 of this chapter compliant labeling must include:

(i) A warning that reads “The assay results are intended to be interpreted only by a qualified pathologist or cytogeneticist.”

(ii) A warning that reads “This device is not for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening.”

(iii) A warning that reads “The use of this device for diagnosis, monitoring or risk assessment has not been established.”

(1) The intended use on the device's label and labeling required under § 809.10 of this chapter must include:

(i) Specimen type;

(ii) Information on the device input(s) (e.g., scanned whole slide images (WSI), etc.);

(iii) Information on the device output(s) (e.g., format of the information provided by the device to the user that can be used to evaluate the WSI, etc.);

(iv) Intended users;

(v) Necessary input/output devices (e.g., WSI scanners, viewing software, etc.);

(vi) A limiting statement that addresses use of the device as an adjunct; and

(vii) A limiting statement that users should use the device in conjunction with complete standard of care evaluation of the WSI.

(3) The labeling required under § 809.10 of this chapter must include the following:

(i) A limiting statement that the result(s) from the device is(are) not intended to be used as the sole basis for a patient diagnosis.

(ii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(vii) of this section that specifically validate an indication for the device's use in guiding blood product use, a limiting statement that the device has not been evaluated to guide blood product use.

(iii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(viii) of this section that specifically validate an indication for the device's use in guiding use of medication, a limiting statement that the device has not been evaluated to guide use of medication.

(2) The 21 CFR 809.10 compliant labeling must include the following:

(i) The intended use statement in the 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include a statement that the results should be interpreted by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings. The intended use statement must also include information on what the device detects and measures, whether the device is qualitative, semi-quantitative, and/or quantitative, the clinical indications for which the device is to be used, and the specific population(s) for which the device is intended.

(ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(iii) of this section and a summary of the results.

(1) The intended use for the device in the labeling required under § 809.10 of this chapter must include a detailed description of the targets the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(6) The 21 CFR 809.10 compliant device labeling must include:

(ii) A detailed explanation of the interpretation of results and limitations regarding the need for review of culture plates by a qualified microbiologist, as appropriate.

(iii) A summary of performance data obtained from the analytical studies used to support device performance, as appropriate.

(iv) A summary of performance data obtained from clinical studies performed on a population that is consistent with the intended use population, as appropriate.

(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of microorganisms and types of human specimens intended to be preserved.

(1) The intended use on the device's label and labeling required under § 809.10 of this chapter must include a detailed description of the type(s) of human specimens intended for collection and preservation, and the characteristics of the microbial population intended for subsequent analysis.

(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling.

(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.

(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: analytes the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.

(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes the device detects, the specimen types tested, the results provided to the end user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use, as appropriate.

(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: analytes the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), and other conditions of use as appropriate.

(1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(1) The intended use for the labeling required under § 809.10 of this chapter must include a description of what the device detects and measures, the specimen types, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.

(3) Your 21 CFR 809.10 compliant labeling must include:

(i) A warning statement that reads “The device is for use by a trained operator in a clinical laboratory setting”;

(ii) A warning statement that reads “All software-aided results must be confirmed by the trained operator”;

(iii) A warning statement that reads “This device is only for use with reagents that are indicated for use with the device”; and

(iv) A description of the protocol and performance studies performed in accordance with paragraph (b)(2)(ii) of this section and a summary of the results, if applicable.

(2) The labeling required under § 809.10 of this chapter must include:

(i) A warning statement that the device is not intended to be used for standalone diagnostic purposes, pre-implantation or prenatal testing or screening, population screening, or for the detection of, or screening for, acquired or somatic genetic aberrations;

(ii) Limitations regarding the assay's performance with respect to validated CNVs reported at the lower range of the assay, stratified by size range and range of probe numbers for gains and losses separately; and limitations regarding problematic (hypervariable) regions, loss of heterozygosity, mosaicism, and inability to detect balanced translocations, as appropriate;

(iii) A warning statement that interpretation of assay results is intended to be performed by qualified healthcare professionals such as clinical cytogeneticists or molecular geneticists; and,

(iv) A description of the performance studies performed in accordance with paragraph (b)(1)(ii) of this section and a summary of the results.

(2) Your § 809.10 compliant labeling must include:

(i) A warning statement that reads “This test is not intended for diagnostic use, preimplantation or prenatal testing, or for screening of SCID-like syndromes, such as DiGeorge syndrome or Omenn syndrome. It is also not intended to screen for less acute SCID syndromes, such as leaky SCID or variant SCID.”;

(ii) A warning statement that reads “Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods and clinical evaluation, as appropriate.”;

(iii) A description of the performance studies listed in paragraph (b)(1)(iii) and a summary of the results; and

(4) Your 21 CFR 809.10 compliant labeling and any test report generated must include the following warning and limitation statements, as applicable:

(i) A warning that reads “The test is intended only for autosomal recessive carrier screening in adults of reproductive age.”

(ii) A statement accurately disclosing the genetic coverage of the test in lay terms, including, as applicable, information on variants not queried by the test, and the proportion of incident disease that is not related to the gene(s) tested. For example, where applicable, the statement would have to include a warning that the test does not or may not detect all genetic variants related to the genetic disease, and that the absence of a variant tested does not rule out the presence of other genetic variants that may be disease-related. Or, where applicable, the statement would have to include a warning that the basis for the disease for which the genetic carrier status is being tested is unknown or believed to be non-heritable in a substantial number of people who have the disease, and that a negative test result cannot rule out the possibility that any offspring may be affected with the disease. The statement would have to include any other warnings needed to accurately convey to consumers the degree to which the test is informative for carrier status.

(A) “The results of this test are intended to be interpreted by a board-certified clinical molecular geneticist or equivalent and should be used in conjunction with other available laboratory and clinical information.”

(B) “This device is not intended for disease diagnosis, prenatal testing of fetuses, risk assessment, prognosis or pre-symptomatic testing, susceptibility testing, or newborn screening.”

(iv) For over-the-counter tests, a statement that reads “This test is not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On its own, this test is also not intended to tell you anything about the health of your fetus, or your newborn child's risk of developing a particular disease later on in life.”

(A) “This test is not a substitute for visits to a healthcare provider. It is recommended that you consult with a healthcare provider if you have any questions or concerns about your results.”

(B) “The test does not diagnose any health conditions. Results should be used along with other clinical information for any medical purposes.”

(C) “The laboratory may not be able to process your sample. The probability that the laboratory cannot process your saliva sample can be up to [actual probability percentage].”

(D) “Your ethnicity may affect how your genetic health results are interpreted.”

(vi) For a positive result in an over-the-counter test when the positive predictive value for a specific population is less than 50 percent and more than 5 percent, a warning that reads “The positive result you obtained may falsely identify you as a carrier. Consider genetic counseling and followup testing.”

(vii) For a positive result in an over-the-counter test when the positive predictive value for a specific population is less than 5 percent, a warning that reads “The positive result you obtained is very likely to be incorrect due to the rarity of this variant. Consider genetic counseling and followup testing.”

(1) The 21 CFR 809.10 compliant labeling and any prepurchase page and test report generated, unless otherwise specified, must include:

(A) The limiting statement explaining that this test provides genetic risk information based on assessment of specific genetic variants but does not report on a user's entire genetic profile. This test [does not/may not, as appropriate] detect all genetic variants related to a given disease, and the absence of a variant tested does not rule out the presence of other genetic variants that may be related to the disease.

(B) The limiting statement explaining that other companies offering a genetic risk test may be detecting different genetic variants for the same disease, so the user may get different results using a test from a different company.

(C) The limiting statement explaining that other factors such as environmental and lifestyle risk factors may affect the risk of developing a given disease.

(D) The limiting statement explaining that some people may feel anxious about getting genetic test health results. This is normal. If the potential user feels very anxious, such user should speak to his or her doctor or other health care professional prior to collection of a sample for testing. This test is not a substitute for visits to a doctor or other health care professional. Users should consult with their doctor or other health care professional if they have any questions or concerns about the results of their test or their current state of health.

(E) Information about how to obtain access to a genetic counselor, board-certified clinical molecular geneticist, or equivalent health care professional about the results of a user's test.

(F) The limiting statement explaining that this test is not intended to diagnose a disease, tell you anything about your current state of health, or be used to make medical decisions, including whether or not you should take a medication or how much of a medication you should take.

(G) A limiting statement explaining that the laboratory may not be able to process a sample, and a description of the next steps to be taken by the manufacturer and/or the customer, as applicable.

(ii) A section in your 21 CFR 809.10 labeling and any test report generated that is for health care professionals who may receive the test results from their patients with the following information:

(A) The limiting statement explaining that this test is not intended to diagnose a disease, determine medical treatment, or tell the user anything about their current state of health.

(B) The limiting statement explaining that this test is intended to provide users with their genetic information to inform lifestyle decisions and conversations with their doctor or other health care professional.

(C) The limiting statement explaining that any diagnostic or treatment decisions should be based on testing and/or other information that you determine to be appropriate for your patient.

(1) The intended use on the device's label and labeling required under § 809.10 of this chapter must include:

(i) The indicated variant types for which acceptable, as determined by FDA, validation data has been provided. Distinct variant types are considered as single nucleotide variant, insertion, deletion, tandem repeats, copy number variants, or gene rearrangements, and validated for specific sizes and lengths, as applicable.

(ii) The indicated specimen type(s) for which acceptable, as determined by FDA, validation data has been provided.

(2) Your 21 CFR 809.10 compliant labeling must include the following:

(i) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) complaint labeling must include an indication for use statement that reads “This test is not intended for the diagnosis of CML”; and

(ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(iii) of this section and a summary of the results.

(2) The 21 CFR 809.10 compliant labeling and any product information and test report generated, must include the following, as applicable:

(i) The intended use statement must specify the following:

(B) The intended specimen type(s) and matrix (e.g., formalin-fixed, paraffin-embedded tumor tissue).

(C) The mutation types (e.g., single nucleotide variant, insertion, deletion, copy number variation or gene rearrangement) for which validation data has been provided.

(ii) A description of the device and summary of the results of the performance studies performed in accordance with paragraphs (b)(1)(iii), (b)(1)(iv), and (b)(1)(v) of this section.

(iii) A description of applicable test limitations, including, for device specific mutations validated with method comparison data to a medically established test in the same intended specimen type, appropriate description of the level of evidence and/or the differences between next generation sequencing results and results from the medically established test (e.g., as described in professional guidelines).

(iv) A listing of all somatic mutations that are intended to be detected by the device and that are reported in the test results under the following two categories or equivalent designations, as appropriate: “cancer mutations panel with evidence of clinical significance” or “cancer mutations panel with potential clinical significance.”

(v) For mutations reported under the category of “cancer mutations panel with potential clinical significance,” a limiting statement that states “For the mutations listed in [cancer mutations panel with potential clinical significance or equivalent designation], the clinical significance has not been demonstrated with adequate clinical evidence (e.g., by professional guidelines) in accordance with [paragraph (b)(1)(v) of this section] or with this test.”

(vi) For mutations under the category of “cancer mutations panel with evidence of clinical significance,” or equivalent designation, link(s) for physicians to access internal or external information concerning decision rules or conclusions about the level of evidence for clinical significance that is associated with the marker in accordance with paragraph (b)(1)(v) of this section.

(1) The labeling required under § 809.10 of this chapter and any pre-purchase page and test report generated, unless otherwise specified, must include:

(i) The specific variants must be appropriately validated as described in paragraphs (b)(4)(xii) and (b)(4)(xiii) of this section.

(A) A warning statement accurately disclosing the genetic coverage of the test in lay terms, including information on variants not queried by the test, and the proportion of pathogenic variants in the genes that the assay detects in a specific population as identified in paragraph (b)(1)(i) of this section. The warning statement must indicate that the test [does not/may not, as appropriate] detect all genetic variants related to the genetic disease, and that the absence of a variant tested does not rule out the presence of other genetic variants that may impact cancer risk. The warning statement must also include the relevant population for which the variants reported by the test are most relevant.

(B) A limiting statement explaining that some people may feel anxious about getting genetic test health results. This is normal. If the potential user feels very anxious, such user should speak to his or her doctor or other healthcare professional prior to collection of a sample for testing. This test is not a substitute for visits to a doctor or other healthcare professional. Users should consult with their doctor or other healthcare professional if they have any questions or concerns about the results of their test or their current state of health.

(C) A limiting statement that a user's ethnicity may affect whether the test is relevant for them and may also affect how their genetic health results are interpreted.

(D) A warning statement that the test is not a substitute for visits to a healthcare professional for recommended screenings, and should not be used to determine any treatments or medical interventions.

(E) A warning statement that the test does not diagnose cancer or any other health conditions and should not be used to make medical decisions. The warning statement must indicate that the results should be confirmed in a clinical setting before taking any medical action.

(F) A limiting statement explaining that other companies offering a genetic risk test may be detecting different genetic variants for the same disease, so the user may get different results using a test from a different company.

(G) If applicable, a limiting statement that states the test does not test for variants in other genes linked to hereditary cancer.

(H) A limiting statement explaining that this test does not account for non-genetic factors and that other factors such as environmental and lifestyle risk factors may affect the risk of developing a given disease.

(I) Information to a potential purchaser or actual test report recipient about how to obtain access to a board-certified clinical molecular geneticist or equivalent to assist in pre- and post-test counseling.

(J) A limiting statement explaining that this test is not intended to tell you anything about your current state of health, or be used to make medical decisions, including whether or not you should take a medication or how much of a medication you should take.

(K) A limiting statement explaining that the laboratory may not be able to process a sample, and a description of the next steps to be taken by the manufacturer and/or the customer, as applicable.

(iii) A section in the labeling required under § 809.10 of this chapter and any test report generated that is for healthcare professionals who may receive the test results from their patients with the following information:

(A) A limiting statement explaining that this test is not intended to diagnose a disease, determine medical treatment or other medical intervention, or tell the user anything about their current state of health.

(B) A limiting statement explaining that this test is intended to provide users with their genetic information to inform health-related lifestyle decisions and conversations with their doctor or other healthcare professional.

(C) A limiting statement explaining that any diagnostic or treatment decisions should be based on confirmatory prescription testing and/or other information that is determined to be appropriate for the patient (e.g., additional clinical testing and other risk factors that may affect individual risk and health care).

(d) The labeling of general purpose laboratory reagents (e.g., hydrochloric acid) and equipment (e.g., test tubes and pipettes) whose uses are generally known by persons trained in their use need not bear the directions for use required by § 809.10(a) and (b), if their labeling meets the requirements of this paragraph.

(1) The label of a reagent shall bear the following information:

(ii) A declaration of the established name (common or usual name), if any, and quantity, proportion or concentration of the reagent ingredient (e.g., hydrochloric acid: Formula weight 36.46, assay 37.9 percent, specific gravity 1.192 at 60 °F); and for a reagent derived from biological material, the source and where applicable a measure of its activity. The quantity, proportion, concentration or activity shall be stated in the system generally used and recognized by the intended user, e.g., metric, international units, etc.

(iii) A statement of the purity and quality of the reagent, including a quantitative declaration of any impurities present. The requirement for this information may be met by a statement of conformity with a generally recognized and generally available standard which contains the same information, e.g., those established by the American Chemical Society, U.S. Pharmacopeia, National Formulary, National Research Council.

(iv) A statement of warnings or precautions for users as established in the regulations contained in 16 CFR part 1500 and any other warnings appropriate to the hazard presented by the product; and a statement “For Laboratory Use.”

(v) When applicable, these instructions shall include such information as conditions of temperature, light, humidity, and other pertinent factors. The basis for such information shall be determined by reliable, meaningful, and specific test methods such as those described in § 211.166 of this chapter.

(vi) A declaration of the net quantity of contents, expressed in terms of weight or volume, numerical count, or any combination of these or other terms which accurately reflect the contents of the package. The use of metric designations is encouraged, wherever appropriate.

(viii) A lot or control number, identified as such, from which it is possible to determine the complete manufacturing history of the product.

(ix) In the case of immediate containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, and which are packaged within an outer container from which they are removed for use, the information required by paragraphs (d)(1)(ii), (iii), (iv), (v), and (vi) of this section may appear in the outer container labeling only.

(2) The label of general purpose laboratory equipment, e.g., a beaker or a pipette, shall bear a statement adequately describing the product, its composition, and physical characteristics if necessary for its proper use.

(4) The outer box label required under § 809.10(a) of this chapter must include the following:

(i) A description of who may use the test, including the presence of symptoms, the days post symptom onset and age restrictions (as applicable);

(ii) A list of the components included with the test;

(iii) A list of the components required to run the test, but not provided;

(iv) A statement that persons with risk factors for severe disease from respiratory pathogens should consult and follow-up with a healthcare provider.

(2) Your 21 CFR 809.10(a) compliant label and 21 CFR 809.10(b) compliant labeling must include warnings relevant to the assay including:

(i) A warning statement that reads, “The device is for use by laboratory professionals in a clinical laboratory setting”;

(ii) A warning statement that reads, “The test is not a stand-alone test but an adjunct to other clinical information. A diagnosis of Type 1 diabetes mellitus should not be made on a single test result. The clinical symptoms, results on physical examination, and laboratory tests (e.g., serological tests), when appropriate, should always be taken into account when considering the diagnosis of Type 1 diabetes mellitus and Type 2 diabetes mellitus”;

(iii) A warning statement that reads, “Absence of Zinc T8 autoantibody does not rule out a diagnosis of Type 1 diabetes mellitus”; and

(iv) A warning statement that reads, “The assay has not been demonstrated to be effective for monitoring the stage of disease or its response to treatment.”

(2) The label required under § 809.10(a) and labeling required under § 809.10(b) of this chapter must include warnings relevant to the assay including:

(i) The device is for use by laboratory professionals in a clinical laboratory setting;

(ii) The test is not a standalone test but an adjunct to other clinical information. A diagnosis of pMGN or secondary MGN should not be made based on a single test result. The clinical symptoms, results on physical examination, and laboratory tests (e.g., serological tests), when appropriate, should always be taken into account when considering the diagnosis of primary versus secondary MGN;

(iii) Absence of circulating PLA2R autoantibody does not rule out a diagnosis of pMGN; and

(iv) The assay has not been demonstrated to be effective for monitoring the stage of disease or its response to treatment.

(2) The 21 CFR 809.10(a) and (b) compliant labeling must include the following limitations:

(i) A limiting statement that this device is not intended to be used a stand-alone device but as an adjunct to other clinical information to aid in the evaluation of patients who are being considered for standard of care neuroimaging.

(ii) A limiting statement that reads “A negative result is generally associated with the absence of acute intracranial lesions. An appropriate neuroimaging method is required for diagnosis of acute intracranial lesions.”

(iii) As applicable, a limiting statement that reads “This device is for use by laboratory professionals in a clinical laboratory setting.”

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(i) The intended use statement in the 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include a statement that the results should be interpreted by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings. The intended use statement must also include information on what the device detects and measures, whether the device is qualitative, semi-quantitative, and/or quantitative, the clinical indications for which the device is to be used, and the specific population(s) for which the device is intended.

(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:

(A) Assayed control material analyte(s);

(B) Whether the material is intended for quantitative or qualitative assays;

(C) Stating if the material is a surrogate control; and

(1) The intended use on the device's label required under § 809.10(a)(2) of this chapter and device's labeling required under § 809.10(b)(2) of this chapter must include a statement that assay results are solely intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, and that reflex testing, clinical genetic evaluation, and genetic counseling should be offered as appropriate.

(i) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) complaint labeling must include an indication for use statement that reads “This test is not intended for the diagnosis of CML”; and

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(2) The intended use required on the label under § 809.10(a)(4) of this chapter and on the labeling required under § 809.10(b)(5)(ii) of this chapter must include a statement that “The test is not intended for use as a stand-alone diagnostic, disease screening, or as a companion diagnostic.”

(2) The intended use for the labeling required under § 809.10(a)(4) of this chapter and for the labeling required under § 809.10(b)(5)(ii) of this chapter, as applicable, must include:

(i) The clinical hematopoietic malignancy for which the assay was designed and validated (e.g., multiple myeloma or B-cell acute lymphoblastic leukemia);

(ii) Specimen type (e.g., bone marrow);

(iii) The specific DNA regions that are being identified and quantified (e.g., rearranged IgH (VDJ), IgH (DJ), IgK, and IgL receptor gene sequences); and

(iv) A statement that the results are indicated to be interpreted by qualified healthcare professionals in accordance with professional guidelines for clinical decision-making in conjunction with other clinicopathological features.

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(1) § 809.10(a)(1) through (a)(6) and (a)(9);

(d) The labeling of general purpose laboratory reagents (e.g., hydrochloric acid) and equipment (e.g., test tubes and pipettes) whose uses are generally known by persons trained in their use need not bear the directions for use required by § 809.10(a) and (b), if their labeling meets the requirements of this paragraph.

(1) The label of a reagent shall bear the following information:

(ii) A declaration of the established name (common or usual name), if any, and quantity, proportion or concentration of the reagent ingredient (e.g., hydrochloric acid: Formula weight 36.46, assay 37.9 percent, specific gravity 1.192 at 60 °F); and for a reagent derived from biological material, the source and where applicable a measure of its activity. The quantity, proportion, concentration or activity shall be stated in the system generally used and recognized by the intended user, e.g., metric, international units, etc.

(iii) A statement of the purity and quality of the reagent, including a quantitative declaration of any impurities present. The requirement for this information may be met by a statement of conformity with a generally recognized and generally available standard which contains the same information, e.g., those established by the American Chemical Society, U.S. Pharmacopeia, National Formulary, National Research Council.

(iv) A statement of warnings or precautions for users as established in the regulations contained in 16 CFR part 1500 and any other warnings appropriate to the hazard presented by the product; and a statement “For Laboratory Use.”

(v) When applicable, these instructions shall include such information as conditions of temperature, light, humidity, and other pertinent factors. The basis for such information shall be determined by reliable, meaningful, and specific test methods such as those described in § 211.166 of this chapter.

(vi) A declaration of the net quantity of contents, expressed in terms of weight or volume, numerical count, or any combination of these or other terms which accurately reflect the contents of the package. The use of metric designations is encouraged, wherever appropriate.

(viii) A lot or control number, identified as such, from which it is possible to determine the complete manufacturing history of the product.

(ix) In the case of immediate containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, and which are packaged within an outer container from which they are removed for use, the information required by paragraphs (d)(1)(ii), (iii), (iv), (v), and (vi) of this section may appear in the outer container labeling only.

(2) The label of general purpose laboratory equipment, e.g., a beaker or a pipette, shall bear a statement adequately describing the product, its composition, and physical characteristics if necessary for its proper use.

(2) § 809.10(b);

(2) The labeling required under § 809.10(b) of this chapter must include a warning statement that the device is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy, and that the device should be used in conjunction with the antral follicle count.

(2) The labeling required under § 809.10(b) of this chapter and any test report generated must include:

(A) Explain that the classification and interpretation of variants identified reflects the current state of scientific understanding at the time the results are issued.

(B) Explain variants could change classification as new scientific information becomes available, which may impact patient eligibility for therapeutic treatment; and

(C) If applicable, explain sufficient scientific information is not available to assign pathogenicity to variants of uncertain significance (VUS).

(ii) A detailed summary of the performance testing, including results, required under paragraphs (b)(1)(i) through (iv) of this section.

(2) The labeling required under § 809.10(b) of this chapter must include:

(A) The test results are not intended to diagnose any disease or condition;

(B) The test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including information obtained by alternative methods, and clinical evaluation, as appropriate; and

(C) The device is not intended for serial monitoring of kidney disease progression or for monitoring the effect of any therapeutic product.

(ii) Limiting statements, where applicable, describing the limitations on the clinical interpretations of the test results.

(iii) Limiting statements, where applicable, describing the limitations to the data generated in the clinical study(ies).

(iv) Detailed information on device performance in relevant subgroups (e.g., severity of chronic kidney disease determined at the beginning of the observation period in the clinical study).

(7) The labeling required under § 809.10(b) of this chapter must include a separate description of the following sensor performance data observed in the clinical study performed in conformance with paragraph (b)(1) of this section for each intended use population, in addition to separate sensor performance data for each different iCGM insertion or use sites (e.g., abdomen, arm, buttock):

(i) less than 54 mg/dL, 54 mg/dL to less than 70 mg/dL, 70 to 180 mg/dL, greater than 180 to 250 mg/dL, and greater than 250 mg/dL.

(iv) A description of the true, false, missed, and correct alert rates and a description of the available glucose concentration alert settings, if applicable.

(8) The labeling required under § 809.10(b) of this chapter must include:

(i) A contraindication for use in pediatric populations except to the extent clinical performance data or other available information demonstrates that it can be safely used in pediatric populations in whole or in part.

(ii) A prominent statement identifying any populations for which use of this device has been determined to be unsafe.

(iii) A prominent statement identifying by name the therapeutic agents that are compatible with the controller, including their identity and concentration, as appropriate.

(iv) The identity of those digitally connected devices with which the controller can be used, including descriptions of the specific system configurations that can be used, per the detailed strategy submitted under paragraph (b)(1)(iii) of this section.

(v) A comprehensive description of representative clinical performance in the hands of the intended user, including information specific to use in the pediatric use population, as appropriate.

(vi) A comprehensive description of safety of the device, including, for example, the incidence of severe hypoglycemia, diabetic ketoacidosis, and other relevant adverse events observed in a study conducted to satisfy paragraph (b)(1)(i) of this section.

(vii) For wireless connection enabled devices, a description of the wireless quality of service required for proper use of the device.

(viii) For any controller with hardware components intended for multiple patient reuse, instructions for safely reprocessing the hardware components between uses.

(3) Your 21 CFR 809.10(b) labeling must include:

(i) The identification of specific insulin formulations that have been demonstrated to be compatible with use of the device;

(ii) A detailed description of the specifications of compatible devices that provide acceptable input data (e.g., continuous glucose monitors, insulin pumps) used to provide accurate and reliable therapy adjustment recommendations;

(iii) A detailed description of all types of required data (inputs) and dosing recommendations (outputs) that are provided by the device; and

(iv) A description of device limitations, and instructions to prevent possible disruption of accurate therapy adjustment recommendations (e.g., time zone changes due to travel).

(2) The labeling required under § 809.10(b) of this chapter must include:

(ii) A warning that indicates that test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate.

(iii) Detailed information on device performance, including the false positive rate and the false negative rate observed in the clinical study.

(iv) Information on device performance in any relevant subgroup (e.g., age of newborn at time of sample collection, birth weight, sex, gestational age, race, ethnicity) observed in the clinical study.

(2) The labeling required under § 809.10(b) of this chapter must include:

(ii) A warning which states that test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate.

(iii) Detailed information on device performance, including the false positive screen rate and the false negative screen rate observed in the clinical study, and any limitations to the data generated in the clinical study (e.g., necessity for testing at a specific age).

(iv) Information on device performance in relevant subgroups (e.g., age of newborn at time of sample collection, birth weight, sex, gestational age) observed in the clinical study.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) Detailed descriptions of the device studies demonstrating the performance of the device, including results; and

(A) The test result is intended as an aid in the management of the patient, and not to be used to replace clinical judgement.

(B) The test result is not to be used to aid in the diagnosis of preeclampsia or conditions resulting from progression of preeclampsia.

(E) The test is not intended to inform the healthcare provider about whether or not changes in immediate treatment, including medication or hospitalization, are needed.

(2) The labeling required under 21 CFR 809.10(b) must include:

(i) A warning statement that test results are not intended to diagnose disease or for monitoring the effect of any therapeutic product.

(ii) A warning statement that test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including information obtained by alternative methods, and clinical evaluation, as appropriate.

(iii) A warning statement that describes any limitations on the clinical interpretation(s) of the test results.

(iv) Detailed information on device performance, including any limitations to the data generated in the clinical study(ies) and information on device performance in relevant subgroups (e.g., severity of liver disease at the beginning of the observation period) observed in the clinical study(ies).

(v) Information on the analytical performance of the device, including demonstration of reproducibility across multiple sites and multiple reagent lots, or an alternative reproducibility study design determined to be appropriate by FDA.

(2) The 21 CFR 809.10(b) compliant labeling must include detailed descriptions of performance testing conducted to evaluate precision, accuracy, linearity, interference, including the following:

(i) Performance testing of device precision must, at a minimum, use intended sample type with Vitamin D concentrations at medically relevant decision points. At least one sample in the precision studies must be an unmodified patient sample. This testing must evaluate repeatability and reproducibility using a protocol from an FDA-recognized standard.

(ii) Performance testing of device accuracy must include a minimum of 115 serum or plasma samples that span the measuring interval of the device and compare results of the new device to results of a reference method or a legally marketed standardized mass spectrometry based vitamin D assay. The results must be described in the 21 CFR 809.10(b)(12) compliant labeling of the device.

(iii) Interference from vitamin D analogs and metabolites including vitamin D2, vitamin D3, 1-hydroxyvitamin D2, 1-hydroxyvitamin D3, 3-Epi-25-Hydroxyvitamin D2, 3-Epi-25-Hydroxyvitamin D3, 1,25-Dihydroxyvitamin D2, 1,25-Dihydroxyvitamin D3, 3-Epi-1,25-Dihydroxyvitamin D2, and 3-Epi-1,25-Dihydroxyvitamin D3, 25, 26-Dihydroxyvitamin-D3, 24 (R), 25-dihydroxyvitamin-D3, 23 (R), 25-dihydroxyvitamin-D3 must be described in the 21 CFR 809.10(b)(7) compliant labeling of the device.

(2) The labeling required under § 809.10(b) of this chapter must include a warning statement as follows: “This assay should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures.”

(2) The device's 21 CFR 809.10(b) compliant labeling must include a detailed description of the protocol, including the information described in paragraph (b)(1)(ii) of this section, as applicable, and a detailed description of the performance studies performed and the summary of the results, including those that relate to paragraph (b)(1)(ii) of this section, as applicable.

(2) The device's § 809.10(b) of this chapter compliant labeling must include a detailed description of the protocol, including the information described in paragraphs (b)(1)(i) through (viii) of this section, as appropriate, and a detailed description of the performance studies performed and the summary of the results, including those that relate to paragraph (b)(1)(ix) of this section, as appropriate.

(3) The labeling required under § 809.10(b) of this chapter must include information that demonstrates the performance characteristics of the test, including a detailed summary of the performance studies conducted and their results, as described in paragraphs (b)(1)(iv) through (xiii) of this section. The labeling required under § 809.10(b) of this chapter must include the pre-specified acceptance criteria for these performance studies, justification for the pre-specified acceptance criteria, and whether the pre-specified acceptance criteria were met.

(2) Labeling compliant with 21 CFR 809.10(b) must include the following:

(i) The intended use statement must include the information described in paragraph (b)(1)(i) of this section, as applicable, and a statement that reads, “It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using this device.”

(ii) A description of the technical studies and the summary of results, including those that relate to paragraphs (b)(1)(ii) and (iii) of this section, as appropriate.

(iii) A description of the performance studies and the summary of results, including those that relate to paragraph (b)(1)(iv) of this section, as appropriate.

(iv) A limiting statement that specifies that pathologists should exercise professional judgment in each clinical situation and examine the glass slides by conventional microscopy if there is doubt about the ability to accurately render an interpretation using this device alone.

(2) The labeling required under § 809.10(b) of this chapter must include:

(A) Detailed descriptions of the software device, including the detection/analysis algorithm, software design architecture, interaction with input/output devices, and necessary third-party software;

(B) Detailed descriptions of the intended user(s) and recommended training for safe use of the device; and

(C) Clear instructions about how to resolve device-related issues (e.g., cybersecurity or device malfunction issues).

(ii) A detailed summary of the performance testing, including test methods, dataset characteristics, results, and a summary of sub-analyses on case distributions stratified by relevant confounders, such as anatomical characteristics, patient demographics, medical history, user experience, and scanning equipment, as applicable.

(A) A description of situations in which the device may fail or may not operate at its expected performance level (e.g., poor image quality or for certain subpopulations), including any limitations in the dataset used to train, test, and tune the algorithm during device development;

(B) The data acquired using the device should only be interpreted by the types of users indicated in the intended use statement; and

(C) Qualified users should employ appropriate procedures and safeguards (e.g., quality control measures, etc.) to assure the validity of the interpretation of images obtained using this device.

(2) The labeling required under § 809.10(b) of this chapter must include the following:

(i) A summary of results from the study required by paragraph (b)(1)(i) of this section, including repeatability, reproducibility, and assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system.

(ii) The claimed measurement range of each parameter (test output), as supported by demonstrated performance of the parameter (test output) throughout the claimed measurement range, including studies required by paragraphs (b)(1)(i) through (iii) and (v) of this section, and, if applicable, paragraphs (b)(1)(vii) and (viii) of this section.

(iii) Identification of known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to each parameter (test output). The information must include the concentration(s) or level(s) at which interference was found to occur and the concentration range or levels at which interference was not found to occur.

(iv) Information regarding the multisite clinical study required by paragraph (b)(1)(v) of this section, including:

(A) Each patient population evaluated;

(B) Each intended use setting and the operators;

(C) A summary of the results, including the concordance analysis to clinically relevant laboratory test(s); and

(2) The labeling required under § 809.10(b) of this chapter must include:

(A) This device should always be used in conjunction with the patient's medical history, clinical presentation, and other laboratory findings.

(B) Identification of any known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to the test outputs. The information must include the concentration(s) or level(s) of the interferent at which clinically significant interference was found to occur, and the concentration range or levels at which interference was not found to occur.

(ii) A detailed summary of the performance testing results of analytical and clinical performance testing, including results of concordance evaluation (overall agreement, positive percentage agreement and negative percentage agreement) as required under paragraph (b)(1) of this section.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) Identification of any known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to the test outputs. The information must include the concentration(s) or level(s) of the interferent at which clinically significant interference was found to occur, and the concentration range or levels at which interference was not found to occur;

(ii) A prominent statement that the device is not intended for use in monitoring patients taking heparin or direct oral factor Xa inhibitors; and

(A) That the device should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures; and

(B) That the device is not specific to the direct oral factor Xa inhibitor that has been evaluated and may detect the presence of other direct factor Xa inhibitors that have not been evaluated.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) Limitations and protocols regarding the need for correlation of results by standard laboratory procedures, as applicable.

(iii) A detailed explanation of the principles of operation and procedures for assay performance and troubleshooting.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed description of the device, including reagents, instruments, ancillary materials, applicable specimen collection and transport device(s) and control elements, and a detailed explanation of the methodology, including all pre-analytical methods for handling and processing of specimens and controls to maintain organism viability;

(ii) Detailed descriptions of the test procedure, including the preparation and maintenance of quality controls and the interpretation of test results;

(iii) Detailed discussion of the performance characteristics of the device for all claimed organisms and specimen types based on analytical studies, including evaluation of analytical sensitivity, inclusivity, cross-reactivity, potentially interfering substances and microorganisms, contamination, specimen stability, precision, and reproducibility;

(iv) Detailed discussion of the performance characteristics of the device observed in a clinical study performed on a population that is consistent with the intended use population in comparison to the results obtained by a reference or comparator method determined to be acceptable by FDA, for microbial detection, identification, and antimicrobial susceptibility testing; and

(v) A limiting statement indicating that a negative test result does not preclude colonization or infection with organisms that do not express detectable levels of the reporter that is identified by the device.

(2) The labeling required under § 809.10(b) of this chapter must include the following:

(i) A detailed device description, including all device components;

(ii) Performance characteristics from applicable analytical studies, including nucleic acid stability and microorganism inactivation;

(iii) A limiting statement that erroneous results may occur when the transport device is not compatible with molecular testing; and

(iv) A limiting statement that the device has only been validated to preserve the representative microorganisms used in the analytical studies.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed device description, including reagents, ancillary reagents required but not provided, and all other parts that make up the device.

(iii) A warning statement that the device should only be used with legally marketed assays that are indicated for use with the device, including, as appropriate, indicated for the relevant storage and transport conditions.

(iv) Description of the microorganisms used for studies, including the results and performance summaries, required under paragraph (b)(3)(i) of this section.

(3) The labeling required under 21 CFR 809.10(b) of this chapter must include:

(A) A detailed description of targets the device detects and measures;

(B) The results provided to the user (i.e., whether the measurement is qualitative, semi-quantitative, or quantitative);

(C) The clinical indications appropriate for test use (e.g., in conjunction with patient history, epidemiological information, clinical observations, and other laboratory evidence to make patient management decisions);

(D) Sample types with which it is intended for use;

(E) The specific population(s) with which the device is intended to be used;

(F) The testing location(s) where the device is to be used (if not intended for all locations);

(G) A statement that the device results are for the presumptive identification of Bacillus spp., and definitive identification requires additional testing and confirmation procedures in consultation with the appropriate public health authorities;

(H) and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions; and

(I) A statement that testing is to be performed and reported in accordance with current guidelines provided by the appropriate public health authorities.

(ii) that may be present in test samples and those used as control materials.

(iii) Detailed instructions for minimizing the risk of generating false positive test results due to contamination from positive test samples and/or positive control materials.

(iv) A prominent and conspicuous precaution that interpretation of test results is intended to be performed by experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and the expertise to report results.

(v) A prominent and conspicuous warning statement that the test results alone do not conclusively establish infection and that additional testing and confirmation procedures may be necessary in consultation with the appropriate public health or other authorities to whom reporting is required.

(vi) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of samples.

(vii) Detailed descriptions of the performance characteristics of the device for all claimed sample types as shown by the analytical and clinical studies required under paragraphs (b)(4)(ii) and (b)(4)(iii) of this section, except sample stability performance characteristics.

(viii) For any devices intended for use in a near-patient setting, a brief reference sheet for healthcare professionals that accompanies the device and that includes the name and intended use of the test, step-by-step instructions of all control and sample testing procedures for the claimed sample types, the result(s) interpretation, warning and limitation statements, and information for troubleshooting or technical assistance with the device.

(ix) A statement that a nationally notifiable disease caused by a biothreat microbial agent must be reported to public health authorities in accordance with local, state, and federal law.

(A) Situations where the device has been demonstrated to fail or may not perform at its expected performance level (e.g., any disease specific circumstances or circumstances identified by human factors or robustness studies);

(B) Any specific circumstances that pose significant risk to public health, and for which the device has not been validated. For example:

(1) Testing of matrices and patient populations that are not identified in the intended use; or

(2) Testing individuals without signs and symptoms of infection, including mass infection screening (such as airport or border screening) that is not limited to individuals who have signs and symptoms and a risk of exposure to biothreat microbial agents.

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the test is not intended for the screening of blood, plasma, and cell or tissue donors.

(ii) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate:

(A) When appropriate, the performance characteristics of the test have not been established in populations of immunocompromised or immunosuppressed patients or, other special populations where test performance may be affected.

(B) The detection of HCV antibodies indicates a present or past infection with hepatitis C virus, but does not differentiate between acute, chronic, or resolved infection.

(C) The specimen types for which the device has been cleared, and that use of the test with specimen types other than those specifically cleared for this device may result in inaccurate test results.

(D) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results.

(E) A non-reactive test result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the test.

(1) For all nucleic acid-based HCV RNA tests, the labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the test is not intended for use as a donor screening test for the presence of HCV RNA from human cells, tissues, and cellular and tissue-based products.

(iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. These limitations must include, but are not limited to, statements that indicate:

(A) The specimen types for which the device has been cleared and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results.

(B) When applicable, that assay performance characteristics have not been established in populations of immunocompromised or immunosuppressed patients or, other populations where test performance may be affected.

(C) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results.

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the assay is not intended for the screening of blood, plasma, cells, or tissue donors.

(iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include statements that indicate:

(A) The specimen types for which the device has been cleared, and that use of this assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results.

(B) When appropriate, performance characteristics of the assay have not been established in populations of immunocompromised or immunosuppressed patients or other populations where assay performance may be affected.

(C) Diagnosis of hepatitis B infection should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures.

(D) Detection of HBV antigens indicates a current infection with hepatitis B virus but does not differentiate between acute or chronic infection. False reactive HbsAg result may occur for up to 2 weeks after vaccination with HbsAg containing vaccine.

(E) Current methods for the detection of hepatitis B antigens may not detect all potentially infected individuals. A non-reactive assay result does not exclude the possibility of exposure to or infection with hepatitis B virus. A non-reactive assay result in individuals with prior exposure to hepatitis B may be due to but not limited to antigen levels below the detection limit of this assay or lack of antigen reactivity to the antibodies in this assay. HBV mutants lacking the ability to produce antigens have been reported. These may occur as “escape” mutants in the presence of anti-HBV antibodies and such patients may be infectious.

(F) Results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay.

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the assay is not intended for the screening of blood, plasma, cells, or tissue donors.

(iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include statements that indicate:

(A) When appropriate, performance characteristics of the assay have not been established in populations of immunocompromised or immunosuppressed patients or other special populations where assay performance may be affected.

(B) Detection of HBV antibodies to a single viral antigen indicates a present or past infection with hepatitis B virus, but does not differentiate between acute, chronic, or resolved infection.

(C) The specimen types for which the device has been cleared, and that use of the assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results.

(D) Diagnosis of hepatitis B infection should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures.

(E) A non-reactive assay result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the assay.

(F) Results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay.

(v) For devices intended for the quantitative detection of HBV antibodies (anti-HBs), in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, labeling required under § 809.10(b) of this chapter must include:

(A) The assay calibrators' traceability to a standardized reference material that FDA has determined is appropriate (e.g., a recognized consensus standard) and the limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity, and precision to define the analytical measuring interval.

(B) Performance results of the analytical sensitivity study testing a standardized reference material that FDA has determined is appropriate (e.g., a recognized consensus standard).

(1) Labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the assay is not intended for use as a screening assay for the presence of HBV DNA in blood or blood products, plasma, cells, or tissue donors, or as a diagnostic assay to confirm the presence of HBV infection.

(iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and/or management. These limitations must include statements that indicate:

(A) Management of patients undergoing HBV treatment should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures, e.g., HBV serologic testing, liver function assays, liver elastography, etc.

(B) The specimen types for which the device has been cleared, and that use of this assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results.

(C) The results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay.

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the device is not intended for use as a donor screening test for the presence of CMV DNA in blood or blood products.

(ii) Limitations, which must be updated to reflect current clinical practice. The limitations must include, but are not limited to, statements that indicate:

(A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results;

(B) Negative test results do not preclude CMV infection or tissue invasive CMV disease, and that CMV test results must not be the sole basis for patient management decisions.

(iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in CMV viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in CMV viral load measurements across different CMV assays, it is recommended that the same device be used for the quantitation of CMV viral load when managing CMV infection in individual patients.”

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use with a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) to be tested.

(ii) A detailed device description, including all device components, instrument requirements, ancillary reagents required but not provided, and an explanation of the methodology, including all pre-analytical methods for specimen processing.

(iii) Performance characteristics from analytical and clinical studies required under paragraphs (b)(2)(ii) and (iii) of this section.

(v) A limiting statement that device results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions.

(vi) As applicable, a limiting statement and specific sample collection recommendations to indicate that breast milk can result in false positive results for saliva samples if samples are collected less than 1 hour after breastfeeding. Sample collection a minimum of 1 hour from breastfeeding must be recommended.

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) A prominent statement that the device is not intended for use as a donor screening test for the presence of viral nucleic acid in blood or blood products.

(ii) Limitations which must be updated to reflect current clinical practice. These limitations must include, but are not limited to, statements that indicate:

(A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; and

(B) Negative test results do not preclude viral infection or tissue invasive viral disease and that test results must not be the sole basis for patient management decisions.

(iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in [analyte] measurements across different [analyte] assays, it is recommended that the same device be used for the quantitation of [analyte] when managing individual patients.”

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use with a detailed description of what the device detects and measures, the type of results provided to the user, the sample type, whether the measure is qualitative and/or quantitative, the clinical indications for the test use, and the specific population(s) for which the device is intended.

(ii) A detailed description of the performance characteristics of the device for all intended specimen types from the analytical and clinical studies (as applicable) required under paragraphs (b)(3)(ii) and (iii) of this section.

(iii) A detailed explanation of the interpretation of results, including acceptance criteria for evaluating the validity of individual runs (e.g., assessment of internal and/or external quality controls, as applicable).

(A) A statement that a negative test result does not preclude the possibility of infection;

(B) A statement that the test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;

(C) A statement that consistent device performance is dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and

(D) A statement that details any limitations associated with the samples, as appropriate (e.g., collected on the day of admission to the intensive care unit).

(2) The labeling required under § 809.10(b) of this chapter must include:

(A) A statement that the device detects and measures bacterial proteases from a swab saturated with wound fluid.

(B) A statement that the device provides a qualitative output to aid the user in assessing the risk for non-healing of wounds (e.g., chronic venous, diabetic foot and pressure ulcers).

(E) A description of the recommended training (e.g., knowledge and experience) for safe and effective use of the device and to minimize the risks of incorrect results and misinterpretation.

(ii) A detailed description of the performance characteristics of the device from the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section.

(iv) A warning statement describing situations where the device has not been validated or may not perform as identified in the labeling (e.g., not for use with wounds which are ≥6 months of age and ≥1 cm 2 in size).

(A) That the device is not intended to provide a risk assessment of chronic wound infection status or aid in the diagnosis of infection in chronic wounds, nor is the device intended for monitoring the effectiveness of anti-infective therapy.

(B) Therefore, the results should be used in conjunction with clinical findings to make an accurate assessment of risk of nonhealing. The test result should be interpreted in conjunction with other risk factors, along with clinical and laboratory data available to the clinician.

(C) Other sample types (e.g., whole blood from venous or capillary draws, other body fluids) have not been evaluated.

(D) That skin flora may secrete bacterial proteases therefore, swab contact with intact skin should be avoided as this may yield false positive results.

(vi) Labeling must include a brief reference sheet for healthcare professionals that includes the intended use, summary of clinical performance, results from analytical testing on normal skin and human proteases, and warning and limiting statements.

(2) The labeling required under § 809.10(b) of this chapter must include, as determined to be appropriate by FDA:

(A) The analyte(s) detected by the device;

(B) Data output of the device (qualitative, semiquantitative, or quantitative);

(C) The specimen types with which the device is intended for use;

(D) The clinical indications appropriate for test use (e.g., in conjunction with endoscopy);

(E) The intended use populations (e.g., signs and symptoms, ethnicity); and

(F) The intended use location(s) (e.g., specific name and location of testing facility or facilities).

(ii) A detailed device description, including reagents, instruments, ancillary materials, specimen collection and transport devices, controls, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.

(C) Patients who test negative for the virus should be managed in accordance with the standard of care, based on the assessment of endoscopy and/or other clinical information by a licensed healthcare professional.

(D) Results of the device are not intended to be used as the sole basis for determining the need for biopsy or for any other patient management decision.

(2) The labeling required under § 809.10(b) of this chapter must include:

(ii) A limiting statement indicating that negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.

(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) A statement that the device is intended to be used in conjunction with clinical history, signs, symptoms, and the results of other diagnostic testing;

(ii) A detailed explanation of the interpretation of results and acceptance criteria for any quality control testing; and

(2) The labeling required under 21 CFR 809.10(b) must include:

(i) A detailed device description, including the parts that make up the device, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology including all pre-analytical methods for processing of specimens.

(ii) Performance characteristics from analytical studies, including analytical sensitivity (Limit of Detection), inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, and specimen stability.

(iii) A statement that the device is intended to be used in conjunction with clinical history, signs and symptoms and the results of other diagnostic tests.

(iv) A detailed explanation of the interpretation of test results and acceptance criteria for any quality control testing.

(v) A limiting statement that negative results do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable.

(ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples.

(iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable.

(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;

(ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate;

(iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;

(A) A negative test result does not preclude the possibility of infection;

(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;

(C) Failure to observe proper procedures in any one of these steps can lead to incorrect results; and

(D) If appropriate (e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and

(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that:

(A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present;

(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora;

(C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and

(D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy.

(1) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use with a detailed description of what the device detects (Zika IgM antibodies, other Zika antibodies, or Zika antigens), the type of results provided to the user, the specimen type for which testing is indicated (e.g., serum, whole blood), the clinical indications appropriate for test use, and the specific population(s) for which the test is intended.

(ii) Performance characteristics from analytical and clinical studies required under paragraphs (b)(2)(ii) and (iii) of this section.

(iii) A detailed explanation of the interpretation of results and criteria for validity of results (e.g., criteria that internal or external quality controls must meet in order for a test/test run to be valid, minimum signal strength that the sample has to yield to be interpretable as a valid result).

(A) Results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. The test results should be interpreted in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence.

(B) Device results are intended to be followed up according to the latest professional guidelines (e.g., recommendations from the Centers for Disease Control and Prevention) for the diagnosis of Zika virus infection.

(D) Specimens can result in false negative results on the device if collected outside of the appropriate response window for specific Zika virus antigens or antibodies, as determined by scientific evidence (e.g., for IgM <7 days post symptom onset (pso) or risk of exposure and if collected past 84 days pso).

(v) Detailed instructions for use that minimize the risk of generating a false positive or false negative result (e.g., co-testing of other matrices).

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use that includes a detailed description of targets the device detects and measures, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(A) Not all pathogens that cause febrile illness are detected by this test and negative results do not rule out the presence of other infections;

(B) Evaluation of more common causes of acute febrile illness should be considered prior to evaluation with this test;

(C) Test results are to be interpreted in conjunction with other clinical, epidemiologic, and laboratory data available to the clinician; and

(D) When using this test, consider patient travel history and exposure risk, as some pathogens are more common in certain geographical locations.

(iii) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.

(iv) Detailed discussion of the performance characteristics of the device for all claimed specimen types as shown by the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section, except specimen stability performance characteristics.

(v) A statement that nationally notifiable results are to be reported to public health authorities in accordance with local, state, and federal law.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed explanation of the interpretation of results and acceptance criteria;

(ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status.

(iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population.

(iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that Candida species and bacterial compositions associated with bacterial vaginosis can be present as part of normal vaginal flora and results should be considered in conjunction with available clinical information.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;

(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies;

(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;

(iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety (e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and

(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population (e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).

(A) A negative test result does not preclude the possibility of infection;

(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;

(C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens;

(D) That positive and negative predictive values are highly dependent on prevalence;

(E) Failure to observe proper procedures in any one of these steps can lead to incorrect results; and

(F) When applicable (e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.

(4) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed and comprehensive device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;

(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: limit of detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, hook-effect, carryover/cross contamination, specimen stability, precision, reproducibility, human factors analysis, flex studies, and clinical studies;

(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;

(iv) A statement in the intended use that positive results do not preclude co-infection with bacteria or other viruses and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions;

(v) Detailed instructions for minimizing the risk of user's exposure to infectious microbial agents that may be present in test specimens and those used as control materials;

(vi) Detailed instructions for minimizing the risk of generating false positive test results due to carry-over contamination from positive test specimens and/or positive control materials, as applicable to the design of the test device;

(vii) A brief reference sheet (Quick Reference Instructions) for the intended user(s) that includes, at a minimum, the name and intended use of the test, easy to follow step-by-step instructions of all control and sample testing procedures for the claimed sample types, including graphic illustrations targeted towards lay users (as applicable), the result(s) interpretation guidance, warnings and limitation statements, toxicology information and safety considerations for any hazardous materials, information for troubleshooting (e.g., Frequently Asked Questions), and technical assistance with the device (e.g., Help-line contact information);

(A) For those devices intended for testing in symptomatic subjects, a statement that specifies the number of days post symptom onset validated for use of the device and/or a range in which the performance of the test is known;

(B) A negative test result does not preclude the possibility of infection with other bacteria or viruses;

(C) The test results should be interpreted in conjunction with other clinical and laboratory data available to the healthcare provider (as applicable);

(D) There is a risk of erroneous results (i.e., false negatives) due to the presence of novel, emerging respiratory viral variants (e.g., specific strains or isolates);

(E) False positive test results are more likely when prevalence of upper respiratory infection is low in the community;

(F) Accurate results are dependent on adequate specimen collection, transport, storage, and processing (as applicable). Failure to observe proper procedures in any one of these steps can lead to incorrect results;

(G) Use of expired tests can lead to incorrect results; and

(H) The performance characteristics for that analyte were established when [insert predominant strain, subtype, or variant] was prevalent and that due to the propensity of the virus to mutate, new strains emerge over time which may affect the performance of this device and have serious public health implications. Additional testing with a molecular test and/or sequencing should be considered in situations where a new virus strain or variant is suspected.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;

(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies, including the following, as applicable: Assay cutoff or limit of detection expressed in international standard units, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover and cross contamination, matrix equivalency, hook effect, specimen stability, precision, reproducibility, and clinical studies, including the time period in which the clinical performance was established and the variant(s) prevalent in the United States at the time of performance validation;

(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;

(iv) When applicable, performance results of the analytical study testing of a standardized reference material that FDA has determined is appropriate;

(A) A negative test result does not preclude the possibility of infection;

(B) A negative result can occur if the quantity of the anti-SARS-CoV-2 antibodies present in the specimen is below the detection limits of the assay, or the antibodies that are detected are not present during the stage of disease in which a sample is collected;

(C) There is a risk of erroneous results (i.e., negative results) due to the presence of novel emerging viral variants circulating in the intended use population;

(D) The performance characteristics for that analyte were established when [insert predominant strain, subtype, or variant] was prevalent and that due to the propensity of the virus to mutate, new strains emerge over time which may affect the performance of this device and have serious public health implications;

(E) The test results should be interpreted in conjunction with other clinical and laboratory data available to the healthcare provider (as applicable);

(F) Positive and negative predictive values are highly dependent on prevalence;

(G) Accurate results are dependent on adequate specimen collection, transport, storage, and processing (as applicable). Failure to observe proper procedures in any one of these steps can lead to incorrect results;

(H) The test is not intended for donor screening; and

(I) An assay that directly detects the virus should be used to evaluate individuals for acute COVID-19, particularly those who have been in contact with the virus.

(vi) For devices intended for the quantitative detection of SARS-CoV-2 antibodies, labeling must include a prominent statement that includes the following: the test calibrators' traceability to a standardized reference material that FDA has determined is appropriate and the limit of blank, limit of detection, and limit of quantitation, with the defined analytical measuring interval.

(3) The labeling required under § 809.10(b) of this chapter must include the following:

(i) A statement in the intended use that positive results do not rule out co-infection with other respiratory pathogens;

(ii) Summary instructions and information written in appropriate language for the intended user that includes easy to follow step-by-step instructions for sample testing, explanation of test results, any warnings and precautions relevant to testing, and frequently asked questions (FAQs), as required by paragraph (b)(5)(iii) of this section;

(A) For those devices intended for testing in symptomatic subjects, a specification of the number of days post symptom onset validated for use of the device and/or a range in which the performance of the test is known, where applicable;

(B) Statements that a negative test result does not preclude the possibility of infection with other pathogens, and that a positive test result does not preclude the possibility of co-infection with additional pathogens;

(C) A statement that persons with risk factors for severe disease from respiratory pathogens (e.g., chronic lung or heart disease, compromised immune system, diabetes, and other conditions listed by the Centers for Disease Control and Prevention (CDC)) should consult and follow-up with a healthcare provider, who will advise if additional testing or treatment are necessary;

(D) A statement that the test is not a substitute for consultation with a health care provider and should not be used to determine any treatments without provider supervision. A statement that the healthcare provider will consider additional information such as the patient's personal medical history and symptoms, current disease prevalence in the community, and additional test results if applicable, to help determine what steps are best for diagnosis and treatment if needed;

(E) A statement that it is especially important to discuss any test results with a healthcare provider if any of the following occur:

(1) The symptoms persist or worsen;

(2) The patient has high risk for severe illness based on age or medical condition;

(3) The patient has a condition that makes it difficult to use the test (e.g., problems with vision, handling the test components, or understanding test instructions or results); or

(4) The patient is performing this test on behalf of a person who has any of the above conditions;

(F) A statement that accurate results are dependent on adequate product storage and adherence to the specimen collection and testing procedures. A statement that failure to follow test procedures can lead to incorrect results;

(G) A statement that the test must not be used beyond the expiration date listed on the packaging. A statement that use of expired tests can lead to incorrect results;

(H) A statement that false positive test results are more likely when prevalence of SARS-CoV-2 is low in the community; and

(I) The performance characteristics for SARS-CoV-2 were established when [insert predominant strain, subtype, or variant and timeframe] was dominant. Test accuracy may change as new SARS-CoV-2 viruses emerge. Additional testing with a lab-based molecular test (e.g., polymerase chain reaction (PCR)) should be considered in situations where a new virus or variant is suspected.

(2) The 21 CFR 809.10(b) labeling must include:

(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.

(ii) Performance characteristics from analytical studies, including, but not limited to, limit of detection, inclusivity, reproducibility, cross reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, and linearity, as applicable.

(iii) A limiting statement that the device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing.

(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.

(v) A limiting statement that negative results for microorganisms do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

(vi) If applicable, a limiting statement that detected microorganisms may not be the cause of lower respiratory tract infection and may be indicative of colonizing or normal respiratory flora.

(vii) If applicable, a limiting statement that detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora.

(viii) If applicable, a limiting statement that detection of antibiotic resistance markers may not correlate with phenotypic gene expression.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use that includes a detailed description of targets the device detects and measures, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(A) The device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing;

(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay; and

(C) A not detected result for the antimicrobial resistance gene assays does not indicate antimicrobial susceptibility. Culturing and susceptibility testing of isolates is needed to determine antimicrobial susceptibility.

(iii) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.

(iv) Detailed descriptions of the performance characteristics of the device for all claimed specimen types as shown by the analytical and clinical studies required under paragraphs (b)(3)(iii) and (b)(3)(iv) of this section except specimen stability performance characteristics.

(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or

(2) The device's 21 CFR 809.10(b) compliant labeling must include warnings relevant to the device including:

(i) A warning statement that reads “The device is for use by laboratory professionals in a clinical laboratory setting”; and

(ii) A warning statement that reads “The device is not to be used as a stand-alone device but as an adjunct to other clinical information. A diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD) should not be made on a single test result. The clinical symptoms, results from physical examination, laboratory tests (e.g., serological tests), and radiological tests (e.g. Magnetic Resonance Imaging), when appropriate, should always be taken into account when considering the diagnosis of NMO and NMOSD.”

(2) Your 21 CFR 809.10(a) compliant label and 21 CFR 809.10(b) compliant labeling must include warnings relevant to the assay including:

(i) A warning statement that reads, “The device is for use by laboratory professionals in a clinical laboratory setting”;

(ii) A warning statement that reads, “The test is not a stand-alone test but an adjunct to other clinical information. A diagnosis of Type 1 diabetes mellitus should not be made on a single test result. The clinical symptoms, results on physical examination, and laboratory tests (e.g., serological tests), when appropriate, should always be taken into account when considering the diagnosis of Type 1 diabetes mellitus and Type 2 diabetes mellitus”;

(iii) A warning statement that reads, “Absence of Zinc T8 autoantibody does not rule out a diagnosis of Type 1 diabetes mellitus”; and

(iv) A warning statement that reads, “The assay has not been demonstrated to be effective for monitoring the stage of disease or its response to treatment.”

(2) The label required under § 809.10(a) and labeling required under § 809.10(b) of this chapter must include warnings relevant to the assay including:

(i) The device is for use by laboratory professionals in a clinical laboratory setting;

(ii) The test is not a standalone test but an adjunct to other clinical information. A diagnosis of pMGN or secondary MGN should not be made based on a single test result. The clinical symptoms, results on physical examination, and laboratory tests (e.g., serological tests), when appropriate, should always be taken into account when considering the diagnosis of primary versus secondary MGN;

(iii) Absence of circulating PLA2R autoantibody does not rule out a diagnosis of pMGN; and

(iv) The assay has not been demonstrated to be effective for monitoring the stage of disease or its response to treatment.

(1) The 21 CFR 809.10(b) compliant labeling must include detailed descriptions of and results from performance testing conducted to evaluate precision, accuracy, linearity, analytical sensitivity, interference, and cross-reactivity. This information must include the following:

(i) Performance testing of device precision must, at minimum, use one unmodified clinical specimen from the intended use population with concentration of the brain injury biomarker(s) near the medical decision point. Contrived specimens that have been generated from pooling of multiple samples or spiking of purified analyte to cover the measuring range may be used, but the contrived samples must be prepared to mimic clinical specimens as closely as possible. This testing must evaluate repeatability and reproducibility using a protocol from an FDA-recognized standard.

(ii) Device performance data must be demonstrated through a clinical study and must include the following:

(A) Data demonstrating clinical validity including the clinical sensitivity and specificity, and positive and negative predictive value of the test in the intended use population of patients with suspected mild traumatic brain injury (i.e., Glasgow Coma Score (GCS) of 13-15), or equivalent standard of care for determination of severity of traumatic brain injury (TBI).

(B) Study must be performed using the operators and in settings that are representative of the types of operators and settings for which the device is intended to be used.

(C) All eligible subjects must meet the well-defined study inclusion and exclusion criteria that define the intended use population. The prevalence of diseased or injured subjects in the study population must reflect the prevalence of the device's intended use population, or alternatively, statistical measures must be used to account for any bias due to enrichment of subpopulations of the intended use population.

(D) All eligible subjects must have undergone a head computerized tomography (CT) scan or other appropriate clinical diagnostic standard used to determine the presence of an intracranial lesion as part of standard of care and must also be evaluated by the subject device. All clinical diagnostic standards used in the clinical study must follow standard clinical practice in the United States.

(E) Relevant demographic variables and baseline characteristics including medical history and neurological history. In addition, head injury characteristics, neurological assessments, and physical evidence of trauma must be provided for each subject. This information includes but is not limited to the following: Time since head injury, time from head injury to CT scan, time from head injury to blood draw, GCS score or equivalent, experience of loss of consciousness, presence of confusion, episodes of vomiting, post-traumatic amnesia characteristics, presence of post-traumatic seizures, drug or alcohol intoxication, mechanism of injury, acute intracranial lesion type, neurosurgical lesion, and cranial fracture.

(F) Each CT scan or other imaging result must be independently evaluated in a blinded manner by at least two board-certified radiologists to determine whether it is positive or negative as defined by the presence or absence of acute intracranial lesions. This independent review must be conducted without access to test results of the device. Prior to conducting the review, the criteria and procedures to be followed for scoring the images must be established, including the mechanism for determining consensus.

(G) All the clinical samples must be tested with the subject device blinded to the TBI status and the neurological-lesion-status of the subject.

(H) Details on how missing values in data are handled must be provided.

(I) For banked clinical samples, details on storage conditions and storage period must be provided. In addition, a specimen stability study must be conducted for the duration of storage to demonstrate integrity of archived clinical samples. The samples evaluated in the assay test development must not be used to establish the clinical validity of the assays.

(iii) Performance testing of device analytical specificity must include the most commonly reported concomitant medications present in specimens from the intended use population. Additionally, potential cross-reacting endogenous analytes must be evaluated at the highest concentration reported in specimens from the intended use population.

(iv) Expected/reference values generated by testing a statistically appropriate number of samples from apparently healthy normal individuals.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use that provides a description of the measurand(s) (i.e., AD pathology biomarker(s)) the device measures in the specified human specimens, the results provided to the user (including information to facilitate clinical interpretation of all device outputs), the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(A) This device is not intended to be used as a stand-alone test and the test results must be interpreted in conjunction with other diagnostic tools and clinical information.

(B) The safety and effectiveness of the device have not been established for predicting development of dementia or other neurologic conditions or for monitoring the effect of any therapeutic product.

(C) A positive result is associated with the presence of amyloid plaques or neurofibrillary tangles in the brain but does not establish a diagnosis of AD as would be established by neuropathological examination.

(iii) A detailed summary of the performance testing, including results, required under paragraph (b)(1) of this section.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) A warning that mosaicism detected in one tissue may not reflect mosaicism in other tissues and that the significance of mosaicism should be interpreted with caution in conjunction with other laboratory and clinical information (e.g., sex of patient, diagnostic testing or carrier screening, patient symptoms) and should include appropriate genetic counseling.

(ii) A prominent statement that this test is not indicated for use for fetal diagnostic testing, newborn screening or for stand-alone diagnostic purposes.

(iii) Information that addresses how to interpret different result outputs specific to the technology, such as (peaks) in the electropherograms.

(2) The labeling required under § 809.10(b) of this chapter must include:

(A) A detailed description of the target(s) the device detects; and

(A) This test is not intended to screen for SMA subtypes other than those specifically stated in the intended use, nor is it intended for carrier screening, as a stand-alone diagnostic test, or for determining eligibility for therapeutic products.

(B) Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation of presumptive positive results by diagnostic confirmatory testing and clinical evaluation, as appropriate.

(iii) Description of the device information required under paragraphs (b)(1)(i) through (iv) of this section.

(iv) A summary of the results of the studies required under paragraphs (b)(1)(v)(A) through (G) of this section.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) The identification of, or the specifications for, the collection device or devices to be used for sample collection, as applicable.

(ii) A description of the reportable range, which is the region of the genome for which the assay is intended to provide results, as well as a description of the targeted regions of the genome that have enhanced coverage. This must include a description of any genomic regions that are excluded from the reportable region due to unacceptable risk of erroneous results, or for other reasons. A description of the clinically relevant genes excluded from the reportable range must also be included, if applicable.

(iii) A description of the design features and control elements, including the quality metrics and thresholds which are used for reporting the analytical range (the genomic DNA in the reportable range that passed the quality metrics in the run required for reporting to the user) that are incorporated into the testing procedure, that mitigate the risk of incorrect clinical results. The following metrics are considered applicable in the generation of high confidence data and the established thresholds for these metrics for reporting must be described and be determined to be acceptable by FDA: cluster density and percent of cluster pass quality filter, percent of bases meeting the minimum base quality score, average coverage of reads, percent of reads mapped on target, percent of reportable region with coverage meeting the minimum requirement, percent of unassigned read indices, percent of reads for non-human DNA, allele fraction, and strand bias. Any alternate metrics used must be described and an acceptable, as determined by FDA, rationale for applicability must be provided.

(iv) A representative sample of the device output report(s) provided to users, which must include any relevant limitations of the device, as determined applicable by FDA.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use statement, including an indication for use that includes the variant(s) for which the assay was designed and validated, for example, JAK2 G1849T.

(ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(ii) of this section and a summary of the results.

(3) The labeling required under § 809.10(b) of this chapter must include information that demonstrates the performance characteristics of the test, including a detailed summary of the performance studies conducted and their results, as described in paragraphs (b)(1)(iv)(A) through (I) of this section.

(2) The labeling required under § 809.10(b) of this chapter must include:

(A) The intended specimen type(s) for which acceptable, as determined by FDA, validation data has been provided (e.g., peripheral whole blood).

(B) The identification of, or the specifications for, the collection device or devices to be used for sample collection.

(C) Information on the device output(s) (e.g., circulating tumor cells (CTCs), other blood cells).

(E) A statement for general downstream diagnostic assays and that end users need to validate use with any subsequent tests and collection devices.

(F) A statement that the standalone device is not intended for diagnostic, prognostic, or monitoring use with CTCs, including as an aid in any disease management and/or treatment decisions.

(A) The use of the device is intended for the collection of CTCs from previously diagnosed cancer patients.

(D) The performance characteristics of this device have not been established for general downstream diagnostic assays and that end users need to validate use with any subsequent tests and collection devices.

(E) An insufficient number of CTCs or even no circulating tumor cells may be collected.

(F) Results from the standalone device do not provide information to the patient regarding their current state of health.

(G) The standalone device does not diagnose any health conditions and is not a substitute for visits to a doctor or other healthcare professional.

(H) The device is intended only for enriching CTC content in specimens so that the enriched specimens can then be used in further processing/analysis using additional independent methods.

(I) The variability of the number of CTCs and other cells harvested by the device may impact the success of any subsequent analysis.

(iv) A troubleshooting section that includes clear instructions for resolving any common device-related issues.

(vi) A detailed summary of the analytical and clinical performance studies required under paragraph (b)(3) of this section.

(i) The intended use statement in the 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include a statement that the results should be interpreted by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings. The intended use statement must also include information on what the device detects and measures, whether the device is qualitative, semi-quantitative, and/or quantitative, the clinical indications for which the device is to be used, and the specific population(s) for which the device is intended.

(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:

(A) Assayed control material analyte(s);

(B) Whether the material is intended for quantitative or qualitative assays;

(C) Stating if the material is a surrogate control; and

(1) The intended use on the device's label required under § 809.10(a)(2) of this chapter and device's labeling required under § 809.10(b)(2) of this chapter must include a statement that assay results are solely intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, and that reflex testing, clinical genetic evaluation, and genetic counseling should be offered as appropriate.

(i) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) complaint labeling must include an indication for use statement that reads “This test is not intended for the diagnosis of CML”; and

(2) The intended use required on the label under § 809.10(a)(4) of this chapter and on the labeling required under § 809.10(b)(5)(ii) of this chapter must include a statement that “The test is not intended for use as a stand-alone diagnostic, disease screening, or as a companion diagnostic.”

(2) The intended use for the labeling required under § 809.10(a)(4) of this chapter and for the labeling required under § 809.10(b)(5)(ii) of this chapter, as applicable, must include:

(i) The clinical hematopoietic malignancy for which the assay was designed and validated (e.g., multiple myeloma or B-cell acute lymphoblastic leukemia);

(ii) Specimen type (e.g., bone marrow);

(iii) The specific DNA regions that are being identified and quantified (e.g., rearranged IgH (VDJ), IgH (DJ), IgK, and IgL receptor gene sequences); and

(iv) A statement that the results are indicated to be interpreted by qualified healthcare professionals in accordance with professional guidelines for clinical decision-making in conjunction with other clinicopathological features.

(iii) Interference from vitamin D analogs and metabolites including vitamin D2, vitamin D3, 1-hydroxyvitamin D2, 1-hydroxyvitamin D3, 3-Epi-25-Hydroxyvitamin D2, 3-Epi-25-Hydroxyvitamin D3, 1,25-Dihydroxyvitamin D2, 1,25-Dihydroxyvitamin D3, 3-Epi-1,25-Dihydroxyvitamin D2, and 3-Epi-1,25-Dihydroxyvitamin D3, 25, 26-Dihydroxyvitamin-D3, 24 (R), 25-dihydroxyvitamin-D3, 23 (R), 25-dihydroxyvitamin-D3 must be described in the 21 CFR 809.10(b)(7) compliant labeling of the device.

(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.

(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.

(4) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.

(3) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.

(6) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.

(6) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.

(iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling required under § 809.10(b)(9) of this chapter must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required follow up actions or retesting in the case of an unusual or unexpected device result.

(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.

(ii) Performance testing of device accuracy must include a minimum of 115 serum or plasma samples that span the measuring interval of the device and compare results of the new device to results of a reference method or a legally marketed standardized mass spectrometry based vitamin D assay. The results must be described in the 21 CFR 809.10(b)(12) compliant labeling of the device.

(2) Your § 809.10(b)(12) of this chapter compliant labeling must include a statement summarizing the data identified in paragraphs (b)(1)(xiii) through (xviii) of this section and a description of the studies supporting the information, including the pre-specified acceptance criteria for these performance studies, justification for the pre-specified acceptance criteria, and whether the pre-specified acceptance criteria were met.

Data and information submitted under § 809.10(c) that are shown to fall within the exemption established in § 20.61 of this chapter shall be treated as confidential by the Food and Drug Administration and any person to whom the data and information are referred. The Food and Drug Administration will determine whether information submitted will be treated as confidential in accordance with the provisions of part 20 of this chapter.

(3) A diagnostic device, if the sponsor complies with applicable requirements in § 809.10(c) and if the testing:

(i) Is noninvasive,

(ii) Does not require an invasive sampling procedure that presents significant risk,

(iii) Does not by design or intention introduce energy into a subject, and

(iv) Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.

(3) § 809.10(c)(2);

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(4) § 809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and (d)(2); and

(c) ASR's must be labeled in accordance with § 809.10(e).

(2) In the case of immediate containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, and which are packaged within an outer container from which they are removed for use, the information required by paragraphs (e)(1) through (e)(6) of this section may appear in the outer container labeling only.

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(5) § 809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi).

(2) In the case of immediate containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, and which are packaged within an outer container from which they are removed for use, the information required by paragraphs (e)(1) through (e)(6) of this section may appear in the outer container labeling only.

(d) All OTC test sample collection systems for drugs of abuse testing shall be labeled in accordance with § 809.10(f) and shall provide an adequate system to communicate the proper interpretation of test results from the laboratory to the lay purchaser.