Facebook Twitter LinkedIn Syndicate. Testing Guidance. Minus Related Pages. Updated Guidance. Get Email Updates. Serologic Tests for Dengue Virus. Minus Related Pages. Updated Guidance. Get Email Updates. To receive email updates about this page, enter your email address: Email Address. In general, you must include the following types of controls:.
A negative sample may serve as a negative control; the negative control is used to rule out contamination or increased background in test reactions.
The positive control must contain DEN antigens or antibodies at levels close to the cutoff of the assay and must be used to control the entire assay process including extraction if appropriate. Examples of acceptable positive assay control materials include:.
The internal control monitors the integrity of the reagents, whether the assay procedure was followed correctly, and the presence of inhibitors in the samples. Examples of acceptable internal control materials include anti-mouse IgG antibodies, biotin, streptavidin, and anti-peroxidase. It may only be needed for assays performed in single test disposable cartridges or tubes.
You must specify the specimen type s that your assay is intended to measure. A specimen has to be collected from the appropriate anatomical site or source at a time in the course of disease when DENV antigen or antibody is likely to be isolated from the specimen.
The quality and quantity of the target analyte can be highly dependent on factors such as specimen source, collection method, handling e. Testing results you provide in your k must validate that the device maintains acceptable performance e. You must state your acceptance criteria for all specimen collection and handling conditions and stability parameters. Follow all applicable state and federal biosafety guidelines for collecting and handling specimens for pathogen identification.
Your k submission must explain how assay cut-off s were determined also see Section 8. The performance of your device using the pre-determined cut-off and equivocal zone, if applicable must be validated in an independent population consistent with the defined intended use of your device also see Section 7.
You must conduct clinical studies to determine the performance of your device for the specific intended uses of your assay. The approach to specimen collection may differ depending on whether the intended use is as an aid in the diagnosis of specific individuals or as an aid in the investigation of suspected DENV outbreaks.
For the diagnosis of individual patients, specimens must be prospectively collected and tested from individuals from the intended use population i. Fresh samples are preferred for these studies although it may be possible to supplement fresh samples with prospectively collected archived specimens2.
To use prospectively collected archived specimens to evaluate your device you must demonstrate that sample freezing or other preservation techniques do not affect analyte stability, that appropriate archives are selected, and that appropriate measures are taken to identify and remove or mitigate any biases in the studies. If you evaluate the assay using specimens that were archived, you must ensure that the specimens are not selectively utilized i.
Samples must be masked during testing to avoid possible bias. The protocol for each clinical study performed must be included in the k submission. Sponsors are strongly encouraged to discuss study protocols with FDA prior to initiation of clinical studies. At a minimum, protocols must include complete patient inclusion and exclusion criteria, the type and number of specimens needed, study procedures, and a detailed statistical analysis plan.
Copies of the original study protocols, protocol modifications, and any other relevant study information must be included in your k submission. We encourage sponsors to contact FDA to request a review of their proposed study protocols and the selection of specimen type as part of the pre-Submission review process.
This is particularly recommended in a situation where different intended uses of the test may be studied or sponsors are planning to submit a k submission for the first time. Serum and plasma specimens are appropriate sample matrices for this device. Contacting FDA is indicated if other sample types will be studied. Specimens must be collected sequentially from all patients at each study site who meet the specific study inclusion criteria. The total number of samples you must include in your study will depend on anticipated assay performance and the prevalence of DEN disease in the study population.
For the intended use of individual patient diagnosis, you must conduct your studies at a minimum of three different geographical sites representing testing environments where the device will ultimately be used e. At least one of the study sites must be located in the United States. It is recommended that sponsors discuss appropriate study sites for the intended use of outbreak investigation with FDA prior to initiating studies since these studies are more likely to use prospectively archived specimens.
DF symptoms include sudden onset of fever, severe headache, pain behind the eyes, body and muscle aches and joint pain, nausea, and vomiting. DHF is characterized by increased vascular permeability, hypovolemia and abnormal blood clotting mechanisms. DHF is a potentially more deadly condition, similar to DF, but after several days the patient becomes irritable, restless, and sweaty, and the condition can progress to plasma leak and hemorrhage.
You must assess and compare the performance of your device to an appropriate reference method or a predetermined algorithm based on composite reference methods i. RT-PCR is likely to be most appropriate. The reference or composite methods must be well-characterized and validated. You must provide published literature or laboratory data in support of the validation for differentiation of the DEN serotypes.
Validation must include LoD and analytical reactivity data. The LoD of the reference assay must be similar to the analytical sensitivity of the submitted device. Sequencing must be performed on both strands of the amplicon i. It is recommended that you contact the FDA for further information regarding the use of nucleic acid amplification test NAAT reference assays and establishing a predetermined algorithm that uses composite reference methods. Analysis must be based on the intended use i.
Study analysis must account for all samples collected. Comparisons of device performance against the reference standard must be included as 2 cell by 2 cell tables. Additional analyses must be included for device performance relative to patient characteristics e. In studies that combine fresh specimens and archived specimens, analyses must compare performance on each specimen type separately and then combined.
All study data must be included in the k submission as Microsoft Excel, delimited text, or as SAS transport files. Data files must include appropriate annotations or separate codebooks and must include all primary and derived variables e.
Description of the statistical methods applied to the data set must be sufficiently detailed to allow interpretation of the lower estimates of the positive agreement that may be acceptable, and may be discussed with FDA prior to initiating clinical studies.
Your 21 CFR This labeling information helps to mitigate the risks identified previously in this guideline to ensure safe and effective use of these devices. All requirements in 21 CFR The intended use must specify that the device is an aid in the diagnosis of DENV infection. You must also specify the DENV serotypes detected by your assay and any additional specific confirmatory measures that are needed to be taken to confirm your test result if your test is presumptive.
The intended use must specify the sample type and the specific population for which the test is intended. In the device description, you must briefly describe the assay methodology and rationale used in this type of device. This section must include a general description of the entire analysis procedure from the collections of patient samples to result reporting.
You must provide clear and concise instructions that delineate the procedures for using the device, and the types of controls that will minimize risks of inaccurate results.
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