(30 days)
The BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel Mini is a multiplexed polymerase chain reaction (PCR) test intended for use with the BIOFIRE® System for the simultaneous, qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swab (NPS) specimens obtained from individuals with signs and symptoms of respiratory tract infection, including COVID-19; (Respiratory menu) or in throat swab (TS) specimens from individuals with signs and symptoms of pharyngitis (Sore Throat menu).
The following analytes are identified and differentiated using the SPOTFIRE R/ST Panel Mini:
Respiratory Menu:
Viruses
Coronavirus SARS-CoV-2
Human rhinovirus
Influenza A virus
Influenza B virus
Respiratory syncytial virus
Sore Throat Menu:
Viruses
Human rhinovirus
Influenza A virus
Influenza B virus
Respiratory syncytial virus
Bacteria
Streptococcus pyogenes (group A Strep)
Nucleic acids from the viral and bacterial organisms identified by this test are generally detectable in NPS/TS specimens during the acute phase of infection. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of respiratory infection and/or pharyngitis is indicative of the presence of the identified microorganism and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
Negative results in the setting of a respiratory illness and/or pharyngitis may be due to infection with pathogens that are not detected by this test, or a respiratory tract infection that may not be detected by an NPS or TS specimen. Positive results do not rule out co-infection with other organisms. The agent(s) detected by the SPOTFIRE R/ST Panel Mini may not be the definite cause of disease.
Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection and/or pharyngitis.
The SPOTFIRE R/ST Panel Mini simultaneously identifies 5 different respiratory viral pathogens in nasopharyngeal swabs (NPS) or 5 different viral and bacterial pharyngitis pathogens in throat swabs (TS) from individuals with signs and symptoms of respiratory tract infections or pharyngitis, respectively, (see Table 1) The SPOTFIRE R/ST Panel Mini is compatible with the BIOFIRE® System, a polymerase chain reaction (PCR)-based in vitro diagnostic system for infectious disease testing. The BIOFIRE System Sottware executes the SPOTFIRE R/ST Panel Mini test and interprets and reports the test results. The SPOTFIRE R/ST Panel Mini was designed to be used in CLIA-waived environments.
A test is initiated by loading Hydration Solution injection solution injection port of the SPOTFIRE R/ST Panel Mini pouch and NPS or TS specimen, mixed with the provided Sample injection port of the SPOTFIRE R/ST Panel Mini pouch and placing it in the SPOTFIRE System. The reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the SPOTFIRE System Software guides the user through the steps of placing the pouch into the instrument, scanning the sample identification, and initiating the run.
The SPOTFIRE System contains coordinated systems of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically-controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.
Nucleic acid extraction occurs within the SPOTFIRE R/ST Panel Mini pouch using mechanical Ivsis followed by purfication using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the SPOTFIRE System performs a nested multiplex PCR that is executed in two stage. During the first stage, the SPOTFIRE System performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent doublestranded DNA binding dye (LC Green® Plus, BioFire Diagnostics). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data.
The SPOTFIRE System Software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the SPOTFIRE R/ST Panel Mini.
This document describes the BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel Mini, a multiplex PCR test.
1. Table of Acceptance Criteria and Reported Device Performance
The document provides extensive analytical performance data rather than a direct comparison of acceptance criteria to reported clinical performance metrics (like PPA and NPA). However, the "Summary of Performance Data" for clinical studies does present sensitivity/PPA and specificity/NPA, which can be interpreted as the reported device performance against implied clinical acceptance criteria.
Clinical Performance Summary (NPS Specimens - Respiratory Menu)
| Analyte | Performance Metric (Prospective) | % | 95% CI |
|---|---|---|---|
| Coronavirus SARS-CoV-2 (PPA) | 71/73 | 97.3 | 90.5-99.2% |
| Coronavirus SARS-CoV-2 (NPA) | 1031/1037 | 99.4 | 98.7-99.7% |
| Human rhinovirus (PPA) | 345/348 | 99.1 | 97.5-99.7% |
| Human rhinovirus (NPA) | 695/767 | 90.6 | 88.3-92.5% |
| Influenza A virus (PPA) | 0/0 (no positive cases identified) | - | - |
| Influenza A virus (NPA) | 1115/1115 | 100 | 99.7-100% |
| Influenza B virus (PPA) | 0/0 (no positive cases identified) | - | - |
| Influenza B virus (NPA) | 1110/1110 | 100 | 99.7-100% |
| Respiratory syncytial virus (PPA) | 26/27 | 96.3 | 81.7-99.3% |
| Respiratory syncytial virus (NPA) | 1086/1088 | 99.8 | 99.3-100% |
Clinical Performance Summary (TS Specimens - Sore Throat Menu)
| Analyte | Performance Metric (Prospective) | % | 95% CI |
|---|---|---|---|
| Human rhinovirus (Sensitivity/PPA) | 202/213 | 94.8 | 91.0-97.1% |
| Human rhinovirus (Specificity/NPA) | 619/662 | 93.5 | 91.4-95.1% |
| Influenza A virus (Sensitivity/PPA) | 35/35 | 100 | 90.1-100% |
| Influenza A virus (Specificity/NPA) | 840/840 | 100 | 99.5-100% |
| Influenza B virus (Sensitivity/PPA) | 4/4 | 100 | 51.0-100% |
| Influenza B virus (Specificity/NPA) | 872/872 | 100 | 99.6-100% |
| Respiratory syncytial virus (Sensitivity/PPA) | 21/24 | 87.5 | 69.0-95.7% |
| Respiratory syncytial virus (Specificity/NPA) | 849/851 | 99.8 | 99.1-99.9% |
| Streptococcus pyogenes (PPA - PCR) | 209/217 | 96.3 | 92.9-98.1% |
| Streptococcus pyogenes (NPA - PCR) | 654/660 | 99.1 | 98.0-99.6% |
| Streptococcus pyogenes (Sensitivity - Culture) | 174/177 | 98.3 | 95.1-99.4% |
| Streptococcus pyogenes (Specificity - Culture) | 654/692 | 94.5 | 92.6-96.0% |
Analytical Acceptance Criteria and Results for key studies:
| Study | Acceptance Criteria | Reported Device Performance (Results) |
|---|---|---|
| Sample Storage and Handling | 100% expected positive results in all samples tested for each organism. Crossing point (Cp) values evaluated and trended across conditions to assess analyte stability. | Positive results were observed in 100% of all TSa samples tested at all conditions evaluated for all SPOTFIRE R/ST Panel Mini analytes. |
| Limit of Detection (LoD) | LoD confirmed when positive results were reported in at least 95% (≥19/20) of replicates tested at 1x LoD, and fewer than 95% (≤18/20) of replicates tested at 0.1x LoD. Equivalent detection in single and multi-analyte samples based on concordance of positive/negative results. | The LoD concentrations for the SPOTFIRE R/ST Panel Mini analytes were confirmed in viable or infectious units and/or nucleic acid copies/mL. The panel accurately detected viruses and bacteria in samples contrived in either VTM or Amies media containing one or multiple organisms. |
| Analytical Reactivity (Inclusivity) | Assay reactivity of each isolate confirmed if positive results were reported for the appropriate analyte in 3/3 or 4/5 replicates tested within 10x LoD. If fewer than 4/5 replicates, additional testing at 100x LoD or higher. Isolates with reactivity limitations noted in product literature. | Analytical reactivity testing demonstrated that the SPOTFIRE R/ST Panel Mini can detect and accurately report results for a diverse collection of isolates from a variety of strains, serotypes, and genotypes with few limitations. (Limitations noted in conclusion include rare S. pyogenes strains not detected). |
| Analytical Specificity (Exclusivity) | On-panel organisms expected positive for target analyte and negative for others. Off-panel organisms expected negative for all panel analytes, unless otherwise indicated. | Three cross-reactivities were identified by empirical and/or in silico evaluations: SARS-CoV-2 with closely related sarbecoviruses, some Bordetella species with Human Rhinovirus (at high concentration), and some bovine/canine picornaviruses with Human Rhinovirus. These limitations are noted in the device labeling. |
| Interference | Primary results evaluated: pass/fail/invalid for internal controls, and analyte positive/negative results. If unexpected result/control failure for one replicate, retested in two additional pouches. | Accurate results for the SPOTFIRE R/ST Panel Mini were reported in the presence of a variety of potentially interfering substances (endogenous, exogenous, technique-specific, microorganisms). |
| Near-LoD/Reproducibility | Minimum of 90% agreement with expected positive results (≥95% desired) for all organisms. Minimum of 95% agreement with expected negative results. | For positive samples, agreement with expected positive results (all systems/sites) was ≥98% for all analytes. Agreement with expected negative results was 100% for all analytes. Total positive agreement nearly identical between BioFire and clinical sites (99.8% vs. 99.0%). |
| Matrix Validation | Equivalent performance between artificial and natural matrices based on agreement of positive and negative results at each test concentration. Considered equivalent if negative results observed at same or similar test concentration. | Equivalent results achieved when samples prepared in natural and artificial NPS or natural and artificial TS matrices and tested with the SPOTFIRE R/ST Panel Mini. |
| Transport Media Validation | Primary metric: percent agreement between candidate medium and control medium (CDC VTM) for each spiked analyte at each test concentration. 100% agreement when testing above LoD and ≥95% at LoD for compatibility. | Equivalent analyte detection observed for all representative analytes when samples were prepared in each of the candidate media types (BD™ Universal Viral Transport, and Remel MicroTest™ M4RT® Multi-Microbe Media) compared to the control medium (CDC VTM). |
| Sample Carry Over | Positive and negative analyte results evaluated. Positive samples expected positive for target and negative for others. Negative samples expected negative for all analytes. | No unexpected positive results were observed in this study. |
2. Sample Sizes and Data Provenance
- Clinical Performance (Test Set):
- NPS Specimens (Respiratory Menu - Prospective): Total of 1115 specimens. The document doesn't explicitly state the country of origin but implies clinical sites (e.g., "as tested by intended users"). This is prospective data.
- NPS Specimens (Respiratory Menu - Archived): Used for some analytes, e.g., Human Rhinovirus (30 positive, 454 negative), Influenza A (59 positive, 423 negative), Influenza B (30 positive, 28 negative), RSV (37 positive, 447 negative). This is retrospective data.
- TS Specimens (Sore Throat Menu - Prospective): Total of 876 specimens for most viral targets. Streptococcus pyogenes had 217 positive (PCR) / 177 positive (Culture) and 660 negative (PCR) / 692 negative (Culture). This is prospective data.
- TS Specimens (Sore Throat Menu - Archived): Used for some analytes, e.g., Human Rhinovirus (2 positive, 57 negative), Influenza A (11 positive, 44 negative), Influenza B (20 positive, 0 negative), RSV (2 positive, 57 negative), Streptococcus pyogenes (39 positive, 10 negative). This is retrospective data.
- TS Specimens (Sore Throat Menu - Contrived): Used for some analytes, e.g., Influenza A (93 positive, 332 negative), Influenza B (49 positive, 333 negative), RSV (50 positive, 381 negative). This would be laboratory-generated data.
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical test set. It mentions using "molecular assays or known specimen composition" as comparator methods for most analytes, and "culture" as the reference method for Streptococcus pyogenes.
4. Adjudication Method
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth or resolving discrepancies in the clinical test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study is mentioned or implied, as this device is an in vitro diagnostic (IVD) PCR test for direct pathogen detection, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply.
6. Standalone Performance
Yes, the studies described are for standalone performance. The BIOFIRE® SPOTFIRE® R/ST Panel Mini provides automated interpretation and reporting of test results based on the PCR assay. It is designed to be used independently to generate a qualitative detection and identification of microbial nucleic acids.
7. Type of Ground Truth Used
- Clinical Performance (Prospective/Archived): The ground truth for most analytes was established using molecular assays or, in some cases, known specimen composition. For Streptococcus pyogenes, culture was also used as a reference method for some comparisons.
- Analytical Performance (LoD, Inclusivity, Exclusivity, Interference, Reproducibility, Matrix Validation, Transport Media Validation, Carry Over): The ground truth was established through known specimen composition (e.g., contrived samples with known concentrations of organisms, presence of interfering substances, specific transport media).
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. This device is a PCR-based test, and its performance is validated through analytical and clinical studies, not typically through a machine learning training phase with a distinct dataset. The "training" in this context refers to the development and optimization of the PCR primers, probes, and reaction conditions.
9. How the Ground Truth for the Training Set Was Established
Given that this is a PCR diagnostic device, not an AI algorithm in the typical sense of needing a "training set" for model learning, this question isn't directly applicable. The "ground truth" for developing and optimizing the PCR assays themselves would have been established through:
- Careful selection and validation of synthetic nucleic acid targets.
- Testing with characterized microbial isolates and clinical samples whose status was confirmed by established reference methods (e.g., sequencing, culture, validated molecular tests).
- In silico analysis of genetic sequences to design primers and probes with high specificity and inclusivity.
§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.
(a)
Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(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.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(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).(vi) Limiting statements that indicate that:
(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) Accurate results are 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
(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) Design verification and validation must include:
(i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains (
e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection.
(iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device (
e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review.
(vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter.
(6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following:
(i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation.
(ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
(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 must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result.
(iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated (
i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.