Global Perspectives: Comparing Regulations for Point of Care Tests in the U.S. and EU

Point of Care tests (POCT) is a term that is widely used to describe IVDs that are used at the same location as the patient, as opposed to an IVD that is used within a laboratory. This can include a wide range of locations including doctor's offices, clinics, patient bedside, near-patient settings, or other locations outside of a traditional laboratory. POCTs have gained popularity globally as they provide faster results to the patient and can help inform patient management decisions without the delays involved in transferring a sample between a patient location (e.g. doctor's office or hospital) and the reference laboratory. Note that a POCT is different from a test for home use (also called a self-test, or over the counter test), where the patient can directly access and use the test within their home environment.

With the increased demand for POCTs, there has been an increase in investment from MedTech companies to design and develop new POCTs that cover a wider range of analytes and can be utilized in a variety of healthcare settings. The development of new tests necessitates that these tests also must go through regulatory approval for the relevant geographic regions.  

In this technical brief, we will explore the complexities of bringing POCTs to market through a comparison of the difference in regulatory requirements between the U.S. FDA and EU IVDR.

Point of Care Tests in the United States

In the U.S., FDA categorizes IVDs according to their complexity. There are three levels of complexity that are determined by FDA after the IVD is cleared: high complexity, moderate complexity, and waived tests. These complexity levels correspond to the type of laboratory that may run the test. The laboratories are certified under the Clinical Laboratory Improvement Amendments (CLIA) program for a certain complexity level: High complexity, moderate complexity, and CLIA waived.

Moderate and high complexity laboratories are subject to inspection, and must meet CLIA quality system standards, quality control and assessment, and personnel requirements.  In contrast, a testing site that only wants to run waived tests would not need to meet the requirements of moderate or high complexity and would instead require only a certificate of waiver from CLIA [1] [2].

A POCT may be categorized as either a moderate complexity or waived test. The appropriate complexity for the test depends on several factors including complexity and risk of erroneous results. When the POCT is designed, the manufacturer must consider whether it can meet the requirements of a waived test as outlined in FDA guidance documents [3] [4] [5]. The complexity of the test, and inclusion of the test requirements for waived tests must be included up front during design and development to ensure that the device can ultimately be cleared at the expected CLIA level.

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POCT in the EU

In the EU, POCT are not recognized as a type of test under the EU In Vitro Diagnostic Regulation (IVDR). Instead, the term "device for near-patient testing" is used [6]. The IVDR defines near-patient tests (NPTs) as any device that is not intended for self-testing but is intended to perform testing outside of a laboratory environment, generally near to, or at the side of, the patient by a health professional. Unlike in the U.S., there is no laboratory designation level akin to CLIA associated with this type of test. It is typically expected to be used outside of a laboratory environment, but by users who would not be considered "lay persons" but rather "healthcare professionals" such as nurses and physicians.

The IVDR outlines requirements for tests that meet the definition of an NPT. This includes specific labeling requirements as well as design requirements. As with all devices, the IVDR requires that NPTs are designed and developed for the intended purpose, which must be demonstrated through the performance evaluation. For NPTs, this includes a design that considers the competence of the user, as well as instructions for use that are appropriate for the user to apply in order to correctly run the test and interpret the result (GSPR 19). These tests must also account for variation that can be reasonably anticipated in the intended users’ technique and environment. Performance evaluation is expected to include clinical performance in the hands of the intended user, as well as usability studies to ensure that the test can be used as intended.

Bridging the Differences Between EU and US POCT Regulations

For companies looking to gain market access in both the U.S. and EU, the regulatory pathway within one geography may or may not align with the other. Different potential scenarios are outlined below:

• Scenario 1: An IVD for rapid detection of Strep A in throat swabs is CLIA waived by FDA and considered a NPT under IVDR.
  
  
• Scenario 2: A POC Clinical analyzer is CLIA waived in the U.S. for use in POC healthcare settings and is an NPT under IVDR.
  
  
• Scenario 3: A rapid molecular test for identification and differentiation for respiratory infection is moderate/high complexity under FDA and an NPT under IVDR.

Due to the differences in regulation between U.S. and EU, manufacturers of POCT need to be especially careful that the differences in user are considered when planning clinical studies. For Scenario 1, a CLIA waived test in the U.S. does not have any user training requirements associated with it beyond the test instructions. This is in contrast to an NPT in the EU, which would require that the user be "healthcare professionals", and that specific qualifications and training are outlined in the IFU. In the case of a test that is moderate complexity in the U.S., but an NPT in the EU, the opposite problem exists. In the U.S. the POC setting must be CLIA certified, requiring specific training for users as well as a quality system. This is different from an NPT in the EU as IVDR does not have any specific user training like under a CLIA certification, but rather allows the legal manufacturer of the IVD to set their own requirements. There are also no quality system requirements for sites using IVDR certified NPTs.

It is important to consider how the differences in the regulatory landscape and intended user within each of the geographies impacts the design and development pathway for the device. While it can be complicated to design and validate an IVD to support multiple geographies, planning and considering regulatory requirements early in the process will support more efficient market access. The following activities will help outline the path forward for a given POCT.

1. Consider POCT classification in both geographies early such that appropriate design controls can be included up front. For example, CLIA waived will require more simplistic operation versus a test that is cleared for use in a moderate complexity laboratory. The IVDR has requirements regarding the design including a warning if the device has failed to provide an accurate result (GSPR 19.3).
   
   
2. Consider how performance data from the same clinical study can be leveraged for multiple geographies. In order to leverage data across both U.S. and EU, the clinical trial must be designed in such a way to demonstrate both regulatory scenarios. This may mean running a multi-country clinical trial with sites in both the U.S. and EU. It could also mean collecting information regarding the users within the U.S. clinical study to demonstrate that the appropriate "healthcare professionals" are included to support EU market access. Both FDA and EU notified bodies will expect that the clinical data presented accurately reflects the intended use within their geography, so a combined study needs to be carefully executed to ensure that all requirements are included and that the proper details are gathered to support the indications.
   
   
3. Consider running separate usability studies. The differences in regulatory requirements for labeling as well as intended user demographics in each geography can be mitigated by running separate usability studies, which will help to demonstrate the acceptability of the test for the desired user within each geography. Additionally, the different geographic regions may require different labelling, which should be verified through a usability study. It is good practice to perform summative usability studies prior to starting a prospective clinical study to allow for design changes in response to the outcome of the usability study prior to the pivotal trial.
   
   
4. In the case where a usability study identifies systematic design issues that must be corrected, making these changes prior to the pivotal trial is ideal to avoid additional clinical studies to bridge the design changes.

Conclusion

Navigating the regulatory landscape for POCTs across both the U.S. and the EU requires careful planning and a clear understanding of the unique requirements in each region. While the U.S. CLIA system categorizes tests based on complexity and imposes specific quality and training standards, the EU's IVDR has no clear standards for sites and focuses more on device design and performance in the intended use setting by healthcare professionals. Manufacturers must address these regulatory differences early in the design and development process, ensuring that clinical studies, usability testing, and labeling requirements align with both U.S. and EU standards. By anticipating and integrating these diverse requirements, companies can streamline their path to market and ensure that their POCTs are safe, effective, and accessible in multiple regions. The good news is that we are here to help! Our experts know the ins and outs of bringing POCTs to the market and keeping them there, so contact us today to learn more.

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Sources:

[1] CDC, "Test Complexities," [Online]. Available: https://www.cdc.gov/clia/php/test-complexities/index.html.
[2] FDA, "CLIA Categorizations," [Online]. Available: https://www.fda.gov/medical-devices/ivd-regulatory-assistance/clia-categorizations
[3] FDA, "Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices," [Online]. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-clinical-laboratory-improvement-amendments-1988-clia-waiver-applications.
[4] FDA, "Recommendations for Dual 510(k) and CLIA Waiver by Application Studies," [Online]. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-dual-510k-and-clia-waiver-application-studies.
[5] FDA, "CLIA Waiver by Application," [Online]. Available: https://www.fda.gov/medical-devices/ivd-regulatory-assistance/clia-waiver-application.
[6] "EU Regulation 2017/746 In Vitro Diagnostic Regulation," Official Journal of the European Union, 2017.