An Introduction to Laboratory Regulations – Part II (Testing Complexity)

Last month we reviewed the different federal regulatory agencies responsible for establishing laboratory testing guidelines, and a brief overview of the different roles each department has. This month we’ll attempt to demystify testing complexity (waived, non-waived, PPM) and why testing classification matters. Still to come, we’ll review the optional accreditations available to labs, and how accreditation differs from certification.

For all in vitro diagnostic tests, the FDA is responsible for categorizing each test based on their perceived complexity during the pre-market approval process. From least to most complex, the categorizations are waived, moderate complexity, and high complexity. The reason this is important is because with each jump in test category, the CLIA rules associated with performing testing will change – as will the permit designation required to perform testing. This includes things such as QC requirements, validation testing, and personnel requirements to define who can perform testing in the first place.

Waived tests are considered easy to use, with little to no chance that the test result will provide wrong information or cause harm if it is done incorrectly. This includes over-the-counter tests such as home use urine pregnancy kits, where if the sample is applied incorrectly or in insufficient volume there will simply be no result obtained at all. Many Point of Care tests fall under this category, with testing performed in a wide variety of locations including physician offices, urgent care clinics, imaging centers and nursing homes. Locations performing waived testing only are still required to obtain an appropriate CLIA Certificate of Waiver. (See the reference links at the end for a list of all FDA approved CLIA-Waived tests.)

For waived testing, laboratories must follow the manufacturer’s instructions for testing, including the stated FDA approved intended use, without any deviation. If the procedure is modified, or the test is used with specimens not approved by the FDA – the complexity classification of the test will change from waived to high complexity. A common situation where this occurs is with fingerstick whole blood glucometers. Most device manufacturers on the market today for point of care glucose testing are not FDA approved for use with critically ill patients. Using these waived meters for patients deemed “critically ill” based on your local institution’s designation would change the complexity of testing from waived, to high, for this population of patients as it would be considered “off-label use” – meaning you are using it against FDA recommendations and approved forms of use for the test/instrument.

Another caveat to be mindful of is your local state regulations. Certain states (NY, especially) have very strict rules regarding testing complexity designation. In NY, all tests performed within the same designated laboratory space will have the same testing complexity designation. Meaning that if you have a moderate complexity CBC analyzer in the same room you perform your waived urine pregnancy tests – both are now considered moderate complexity. Even though you’re following the manufacturer’s instructions for the pregnancy kit, using only approved specimen types, and the kit is on the FDA approved CLIA-Waived list – that test is now moderate complexity just because it is in the same room as other higher complexity tests. That same pregnancy kit is considered waived when kept separate in the emergency department, but becomes moderate complexity (or higher) when used in the central laboratory.

Nonwaived tests refer to both moderate and high complexity testing. After the FDA has approved a marketing submission, their CLIA categorization of the test follows by utilizing a scorecard to grade the test complexity on 7 different criteria. All phases of testing (preanalytic, analytic and postanalytic) are evaluated in these steps:

  1. Knowledge – low scores require minimal scientific and technical knowledge to perform the test, and knowledge needed can be easily obtained through on-the-job instruction.
  2. Training & Experience – low scores require minimal training and limited experience to perform the test.
  3. Reagents & Materials Preparation – low scores have stable and reliable reagents, and require no special handling, precautions, or storage conditions. They typically come prepackaged, premeasured, and ready for use; whereas high scores may include manual steps such as volumetric measurements and/or reconstitution.
  4. Characteristics of Operational Steps – low scores have automatically executed steps (such as dispensing specific volumes of sample/reagent, temperature monitoring, or timing of steps); high scores require close monitoring or control, precise temperatures or timing, accurate pipetting or extensive calculations.
  5. Calibration, Quality Control, and Proficiency Testing Materials – low scores have all required reagents, controls and PT material commercially available and products are stable.
  6. Test System Troubleshooting & Equipment Maintenance – low scores have automatic troubleshooting or self-correction of errors (failed internal QC will automatically repeat), or requires minimal judgement. Equipment maintenance will be performed by the manufacturer or is minimal and easily performed, whereas high scores require decision-making and direct intervention to resolve most issues, or maintenance tasks require special skills and abilities.
  7. Interpretation & Judgement – low scores require minimal interpretation and judgement for resolution of problems or determination of test results.

Low scores indicate low complexity, with tests obtaining a total score of ≤12 being categorized as moderate complexity. Tests with final scores >12 are categorized as high complexity.

PPM: Within the category of nonwaived tests is a subcategory referred to as Provider Performed Microscopy (PPM). These are tests that are performed directly by a clinician during a patient visit, and require the use of a microscope limited to bright-field or phase-contrast microscopy. Based on the nature of the sample obtained, testing must be performed immediately at the time of collection as delays could compromise the accuracy of test results. As controls are typically not commercially available for these tests, the testing is restricted to clinicians only as knowledge and judgment is required to confirm testing accuracy and correlation to the clinical presentation.

Tests allowed under a PPM certificate are mostly related to OB/GYN procedures, with a full list available through CMS here:

https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/Downloads/ppmplist.pdf

So why does it matter?

So the next time you receive a request to add a new test at your laboratory, you’ll be armed with a fairly long list of the requirements that come with that test based on its complexity. Coming up next month we’ll discuss the difference between laboratory certification and accreditation, along with the benefits of obtaining accreditation for your lab.

References

  1. Electronic Code of Federal Regulations: https://www.ecfr.gov/cgi-bin/text-idx?SID=1248e3189da5e5f936e55315402bc38b&node=pt42.5.493&rgn=div5
  2. CLIA-Waived Analytes: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/analyteswaived.cfm
  3. CLIA Complexity Database: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCLIA/Search.cfm?sAN=0
  4. FDA Approved Devices: https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm


-Kyle Nevins, MS, MLS(ASCP)CM is one of ASCP’s 2018 Top 5 in the 40 Under Forty recognition program. She has worked in the medical laboratory profession for over 18 years. In her current position, she transitions between performing laboratory audits across the entire Northwell Health System on Long Island, NY, consulting for at-risk laboratories outside of Northwell Health, bringing laboratories up to regulatory standards, and acting as supervisor and mentor in labs with management gaps.

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