CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
This addition to the checklist documents for international laboratories the same thing that is required of U.S. laboratories, Dr. Sarewitz says. “In other words, non-U.S. labs implementing tests or instruments that are approved by a body such as CE need only verify the manufacturer’s performance characteristics and show they can meet the level of performance in the manufacturer’s instructions.”
As always, Dr. Jhaveri adds, “Laboratories must practice to the maximum requirements applicable to their geographic regions.”
If a laboratory performs tests that are not FDA approved or cleared or not approved by an internationally recognized regulatory authority, those tests are considered LDTs and subject to the requirements for test method validation found in COM.40350 “Validation of Test Performance Specifications—Modified FDA-Cleared/Approved Tests and LDTs.”
“This simply says that if a test is not approved, the lab must do a full validation. If the lab modifies an approved test, the modification must be validated,” Dr. Sarewitz says.
COM.40350 now says that for labs not subject to U.S. regulations, this requirement also applies to tests not approved by an internationally recognized regulatory authority and to approved tests that the lab has modified.
Dr. Goodman
Test modification is sometimes so subtle, Dr. Goodman says, that lab personnel may not be aware a modification has been made. “For example, let’s say I have an FDA- or CE-approved method of running a gonorrhea test on a cervical swab, and now I want to run it on a throat swab but my platform hasn’t been approved for that specimen type. That is now a modification of an FDA- or CE-approved test and it becomes an LDT.
“Or let’s say I have an FDA- or CE-approved test to look at alpha mutations in lung cancer using a specific probe but I decide to use a different probe. I’ve now modified the test,” he explains, “and it is no longer FDA or CE approved. In both of those cases I would have to do studies to validate them.”
Even when labs are aware of these subtleties, he says, often clinicians are not. “They’ll bring down a specimen and say, ‘We just want you to run this fluid and see if it has creatinine in it,’ but the fluid is not urine. That would mean changing an FDA- or CE-approved serum test for creatinine into a body fluid test for creatinine, and that would not be FDA or CE approved. That modification would require validation.” With a simple change, he says, it’s easy to turn a cleared or approved test into a modified test or an LDT.
COM.40830 says the lab must maintain a list of LDTs and modified approved tests, and the same is true of labs not subject to U.S. regulations.
The all common checklist says, in COM.40640 “Clinical Claims Validation,” that all claims the laboratory makes must be validated for LDTs and for FDA-cleared or -approved tests for which the claim is not in manufacturer instructions. It now says this requirement applies to labs not subject to U.S. regulations that make clinical claims not included in manufacturer instructions about tests approved by an internationally recognized regulatory authority.
“Many laboratories perform testing without making any clinical claims about their testing. They perform a test, then deliver their results, period,” Dr. Goodman says.
If a lab suggests an FDA-approved or -cleared test may be used for something not in the manufacturer instructions, or if a non-U.S. lab does so for a test approved by an internationally recognized regulatory authority, then the lab has to validate the clinical claim.
“Let’s say a lab has an FDA- or CE-approved blood test that detects some kind of cancer that is detailed in the manufacturer instructions,” Dr. Sarewitz says, “but the lab sends out a memo on its catalog saying the test can be used to detect another condition not in the manufacturer instructions. The lab must show it has done its due diligence and completed studies to support that contention.”
Valerie Neff Newitt is a writer in Audubon, Pa.