Definition of a Pregnancy Test

A urine pregnancy test device is an In-Vitro Diagnostic (IVD) hormonal assay that measures the beta (β) subunit of Human Chorionic Gonadotrophin (hCG) levels in urine. It is also known as a ‘home pregnancy test’, an ‘over-the-counter (OTC) pregnancy test’, or a ‘point-of-care pregnancy test’ if a provider administers the test. The generic device is designed to provide a binomial outcome or a positive or a negative result.

Classification of Pregnancy Tests

The medical device classification for pregnancy tests is based on the perceived risk associated with using the device. The class of the device within a regulatory authority will ultimately determine the choice of its testing pathways and the applicable quality standards and regulatory requirements. The U.S. FDA and Health Canada have classified pregnancy tests as a Class II device (medium risk), and applicable to “substantial equivalence” to marketed or predicate devices (510(k) clearance).

FDA Pathway for Pregancy Devices

Quality Standards

U.S. FDA governs the cGMP requirements for medical devices in part 820 (21 CFR Part 820) and incorporates them into a quality system regulation (QSR). The QSR includes requirements related to the methods, facilities, and controls used in the design, manufacturing, packaging, labeling, storing, and performance and maintenance of medical devices intended for human use. The global equivalent is ISO 13485.

For low-to medium-risk class products, compliance with quality-related regulations often depends on the manufacturer’s declaration. Manufacturers are expected to prepare QMS-controlled technical documentation including a description of product design and manufacturing process.

Note: The proof of industry standard for quality management, ISO 9001, is not satisfactory evidence for compliance with ISO 13485. All ISO 13485 requirements are specific to organizations providing medical devices and are required in many countries as the basis for quality assurance management of IVDs for their registration and regulatory control.

Regulatory Requirements

The level of regulatory scrutiny is determined by the level of the potential risks of medical devices. Since pregnancy tests are classified as class II IVD, a product that intends to launch in the United States market is required to submit a 510(k) application, also known as premarket notification.

‘Substantial equivalence’ is a part of the U.S. FDA 510(k) clearance process, where the manufacturer provides evidence indicating that the product to be marketed is at least as safe and effective as a marketed predicate device. FDA will evaluate the product’s intended use, performance, and labeling for clearance determinations. Upon the receipt of written notification of FDA clearance confirming ‘substantial equivalence’, the product can be marketed in the U.S.

See below for the required elements for FDA 510(k) application:

1. Performance Characteristics/Laboratory Evaluation
   1. Comparison Study/OTC study
      1. FDA recommends using at least 100 fresh, human urine samples.
      2. FDA recommends each subject be tested using a predicate device and the new device by both the subject and the professional.
      3. The lay-user performance should mimic actual use (at-home use), such that the subject performs the sample collection and the test without assistance.
      4. FDA recommends administering a subject questionnaire to collect feedback for each use, ensuring readability, and clarity of package insert.
   2. Data Analysis – FDA recommends determining percent accuracy.
2. Specificity and Interference
   1. Interference studies should be performed for pregnancy tests with common prescription and OTC drugs, endogenous compounds, and varying levels of biological analytes, pH, and specific gravity.
   2. Identify the presence of ‘hook effect’ (extremely high concentration of hCG results in false negative/low result).
   3. FDA recommends performing a specificity study using spiking samples with LH, FSH, or TSH for potential cross-reactivity with the hCG antibody used.
3. Sensitivity/Detection Limit
   1. For qualitative assays, the sensitivity/detection limit is the lowest concentration of the analyte that can be detected by the assay (>95%).
4. Imprecision or Reproducibility Studies (optional)
    
5. Expected Values
   1. A clear statement of the product’s expected performance based on the clinical data. For example ‘the test is capable of detecting pregnancy by the first day of the missed period and no sooner’.
6. Stability Data
   1. Shelf-life and open-vial stability.
   2. A summary of stability data of a product that does not need calibration by the end-user.
7. Labeling
   1. The test instruction must be easy to understand (8th-grade reading level) and contain clear pictures or diagrams to aid end-users.
   2. The user manual must include calibration and quality control instructions.
   3. Device limitations shall be included in the labeling, as needed.
   4. The labeling format should conform to the 21 CFR 809.10 labeling regulations. However, for OTC products, some sections can be simplified and contained within the text without such subheadings.

Below is a checklist of the requirements for premarket submissions for pregnancy tests intended for over-the-counter use:

1. Center for Devices and Radiological Health (CDRH) Premarket Submission Cover Sheet.
2. Truthful and Accurate Statement verbatim as required by 21 CFR 807.87(j). Additions and deletions are not permitted.
3. 510(k) Summary or Statement as required by 21 CFR 807.92 or 21 CFR 807.93 respectively.
4. Indications for Use Form.
5. Sensitivity/Detection Limit Data.
6. Specificity Data including LH, FSH, and TSH.
7. Interfering Substances Data.
8. Comparative Study Data including the following: summary of the study protocol, concentrations of spiked specimens used, data to validate all testing procedures (e.g., urine stream and cup method), and summary of responses to the OTC study questionnaire.
9. Antibody Characterization/Purification Information.
10. Components and Function of Internal Control.
11. Predicate Device Labeling.

Health Canada Pathway for Pregnancy Devices

Quality Standards

Health Canada (HC) requires medical device manufacturers to use a quality system certificate as evidence of compliance with the appropriate regulatory quality system requirement. HC only accepts the Medical Device Single Audit Program (MDSAP) certificate issued by Health Canada-authorized Conformity Assessment Bodies (CAB).

Regulatory Requirements

Since pregnancy tests are categorized as class II medical devices in Canada, a Medical Device Licence (MDL) approval by HC is required for a product to be marketed. For class II devices, the process of obtaining an MDL is usually faster than that for 510(k) clearance. There are different application forms for devices in each class. The submitted class II device application will undergo HC’s administrative screening, regulatory screening, administrative processing, and review process.

HC recommends all manufacturers use the guidance documents and tools available on their website when preparing and submitting the MDL application, as inapplicable, incomplete, or unacceptable applications can significantly delay or result in application rejection.

Conclusion

The pathway to market for your pregnancy test depends on the regulatory authority responsible for the market in which you launch your product. In the US, a pregnancy device is classified by the FDA as a class II medical device and requires a 510(k) application to go to market. In Canada, a pregnancy device is classified by Health Canada as a class II medical device and requires an MDL application in order to go to market.

Need assistance getting a pregnancy device to market in Canada or the United States? dicentra is a Contract Research Organization and Consulting firm which helps medical device companies bring their vital products to market. We have extensive regulatory and clinical experience with Medical Devices in Canada and the United States. We have provided clinical research support and consulting expertise to hundreds of medical device clients. Our combination of clinical and regulatory expertise specific to medical devices means we understand the full product lifecycle better than any of our competitors, to the benefit of our clients and sponsors.

Contact us for assistance in bringing your pregnancy test devices to market.