Description
FDA is issuing thisguidanceto facilitate study designs to establish the performance characteristics of in vitro diagnostic devices (IVDs) intended for the detection, or detection and differentiation, of human papillomaviruses (HPVs). These devices are used in conjunction with cervical cytology to aid in screening for cervical cancer or as first-line primary cervical cancer screening devices. These devices include those that detect a group of HPV genotypes, particularly high risk HPVs, as well as devices that detect more than one genotype of HPV and further differentiate among them to indicate which genotype of HPV is present. Approximately 200 HPV genotypes have been identified, about 40 of which can infect the genital tract [Ref. 1]. Infection with ‘high-risk’ types of HPV is considered a necessary cause of virtually all cervical cancer [Ref. 2]. Approximately fourteen HPV genotypes are considered carcinogenic or “high risk” [Ref. 3 & Ref. 20]. For the remainder of this document, “HPV” refers to a “high risk” HPV, except where otherwise noted. A “high risk HPV test” refers to an HPV IVD device that detects, but does not differentiate between different types of HPV; while a “HPV genotyping test” refers to an HPV IVD device that detects and further differentiates HPV types (some HPV tests provide individual HPV genotyping results in addition to the results of pooled probes).
Scope & Applicability
Product Classes
4Validation of certain in vitro diagnostic devices (IVDs) for emerging pathogens; Validation of certain IVD devices for emerging pathogens
FDA will be evaluating all cytology categories when reviewing data to support the adjunct claim going forward to ensure the safety and effectiveness of HPV IVD devices.
Guidance for establishing performance characteristics of IVD HPV devices.
Generally recommended for Enhanced Documentation; Regulatory classification mentioned for implantable sensors and HPV tests; Mentioned in the context of an in vitro nucleic acid test for CMV DNA.
Stakeholders
3responsible for justifying omission of studies
Provides clinical judgment and conducts assessments for ClinROs.
medical professional requesting HCT/P for urgent need; requesting HCT/P based on urgent medical need
Regulatory Context
Attributes
10Variance component used to present precision study results.
Scientific factor evaluated using epidemiological studies.; Factor #2: Prevalence of an IgE-mediated food allergy in the U.S. population; Key criterion for assessing public health importance of allergens.
calculated based on likelihood ratio and prevalence
statistical parameter used to calculate predictive values
Performance measure for categorical variables in validation.; PPV and NPV are variable by data source and study population characteristics.
Performance metric achieved by the model
used to inform the choice of a biomarker cutoff
the biomarker's clinical sensitivity, specificity, and positive and negative predictive values should be well characterized
Specifications that are directly associated with the intended use of the device.
Approximately fourteen HPV genotypes are considered carcinogenic
Identified Hazards
Hazards
4automated liquid handling systems can pose a risk of contamination within or between test runs
randomizing testing on two cytology samples would not mitigate sampling bias
May lead to delays in timely diagnosis of cervical cancer.
Could lead to unnecessary invasive procedures like colposcopy.
Related CFR Sections (3)
- 21CFR809.10§ 809.10 Labeling for in vitro diagnostic products.
(a) The label for an in vitro diagnostic product shall state the following information, except where such information is not applicable, or as otherwise specified in a standard for a particular product class or as provided in paragraph (e) of this section. Section 201(k) of the act provides that “a Read full regulation →
- 21CFR814.15§ 814.15 Research conducted outside the United States.
(a) Data to support PMA. If data from clinical investigations conducted outside the United States are submitted to support a PMA, the applicant shall comply with the provisions in § 812.28 of this chapter , as applicable.Read full regulation →
- 21CFR814.20§ 814.20 Application.
(a) The applicant or an authorized representative shall sign the PMA. If the applicant does not reside or have a place of business within the United States, the PMA shall be countersigned by an authorized representative residing or maintaining a place of business in the United States and shall identRead full regulation →
See Also (8)
- Recommendations for Premarket Notifications for Lamotrigine and Zonisamide Assays: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Clinical Study Designs for Catheter Ablation Devices for Treatment of Atrial Flutter: Guidance for Industry and FDA Staff (Status: Final)
- FDA Inspections of Clinical Investigators: Guidance For IRBs, Clinical Investigators, and Sponsors (Status: Final)
- In Vitro Diagnostic (IVD) Device Studies - Frequently Asked Questions: Guidance for Industry and FDA Staff (Status: Final)
- The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Exception from Informed Consent Requirements for Emergency Research: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors (Status: Final)
- Design Considerations for Pivotal Clinical Investigations for Medical Devices: Guidance for Industry, Clinical Investigators, Institutional Review Boards and FDA Staff (Status: Final)
- Patient Preference Information - Voluntary Submission, Review in Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and Inclusion in Decision Summaries and Device Labeling: Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders (Status: Final)