(a) Identification. A pharmacogenetic assessment system is a qualitative in vitro molecular diagnostic system intended to detect nucleic acid variants isolated from human specimens for the purpose of assessing the presence of genetic variants that impact the metabolism, exposure, response, risk of adverse events, dosing, or mechanisms of prescription or over-the-counter medications. The intended use of the device must not include an indication for use in supporting or sustaining human life, being of substantial importance in preventing impairment of human health, or presenting a potential, unreasonable risk of illness or injury.

(b) Classification. Class II (special controls). A pharmacogenetic assessment system must comply with the following special controls:

(1) Design verification and validation must include:

(i) Data appropriate, as determined by FDA, to demonstrate the analytical accuracy and reliability of the device in intended use specimens, including precision, reproducibility, accuracy, limits of detection, and interferences. This information must include:

(A) Data demonstrating appropriate, as determined by FDA, reproducibility for each genotype using each claimed sample type. Reproducibility data must be evaluated using specimens collected and processed in a manner consistent with the device's instructions for use, or, as determined by FDA, an appropriate alternative sample panel.

(B) Analytical data demonstrating the limits of detection, including the minimum amount of input deoxy-ribonucleic acid (DNA) that will consistently produce accurate results.

(C) Data demonstrating no clinically significant effects from endogenous and exogenous interferents relevant to each intended use specimen type. Interference data must also include an assessment of potentially interfering genetic sequences (e.g., variants proximal to the variant of interest, pseudogenes).

(D) Validation data appropriate, as determined by FDA, to support specimen collection and handling claims.

(E) Clinical data generated in intended use patient populations demonstrating the pharmacogenetic association between the genetic variant tested and any clinical claims or therapy-related recommendations associated with that genotype.

(ii) Results from an appropriate, as determined by FDA, user comprehension study that demonstrate the intended user can use the device safely. The user comprehension study must be designed to include the following:

(A) Study participants from a statistically sufficient sample size and a demographically diverse (e.g., age, education level) population that is representative of the intended use population and naive to use of the device, and

(B) An evaluation of all result comprehension concepts that are critical for safe use of the device.

(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.

(3) The test report must include an appropriate description of how the test results should be used by healthcare providers who may receive the test results from their patients, as applicable.

(4) Publicly available pre-purchase labeling with unrestricted access that contains the following information must be provided:

(i) A clear description of the test and its technology, the genotypes detected, and relevant clinical claims associated with each genotype;

(ii) A clear description of what information the test will provide. This includes variant information, the limitations associated with the test, and any precautionary information about the test the user should be aware of before purchase; and

(iii) A discussion of answers to frequently asked questions that is sufficient to provide intended users with an appropriate understanding of information specific to each pharmacogenetic association that is claimed.

(5) The genetic test must use a sample collection device that is FDA-cleared or -approved, or classified as 510(k) exempt, with an indication for in vitro diagnostic use in DNA testing.

(6) The intended use of the device must not include an indication for use in supporting or sustaining human life, being of substantial importance in preventing impairment of human health, or presenting a potential, unreasonable risk of illness or injury.