America’s Blood Centers (ABC) responded to the U.S. Food and Drug Administration’s (FDA) proposed laboratory developed tests (LDTs) rule in comments submitted on December 4th. In the laboratory developed tests rule comments, ABC described the potential negative impact of the proposed LDTs rule on both public health and the U.S. blood supply, in addition to its ability to be overly burdensome and, “prohibit patient access to tests necessary to ensure blood compatibility.”
ABC’s laboratory developed tests rule comments to the agency recommended that either blood centers be exempt from the regulation or that FDA revises the proposed LDTs rule to maintain the flexibility of the agency to exercise enforcement discretion over all tests developed and used by blood centers. The LDTs rule comments outlined four specific areas of concern with the regulation including:
- “LDTs developed by blood establishments are not associated with the type of safety concerns FDA is addressing with this rule;
- many LDTs developed in a blood center’s lab are 1976-Type LDTs and/or are developed with a high level of standardization across institutions;
- blood centers’ LDTs are comparable to Human Leukocyte Antigen (HLA) tests. FDA should apply general enforcement discretion to all HLA tests and blood center’s LDTs; [and]
- the impact [of the LDT regulation] on patient access.”
The LDTs rule comments explained that, “blood centers’ LDTs are extremely safe and effective under the current framework and do not have a history of safety issues. Blood centers and hospitals are required to report adverse events to FDA. The safety record of these tests is well-documented in this reporting system, and a mechanism exists to resolve any safety issues that are potentially identified.” Additionally, ABC noted in the laboratory developed tests rule comments that, “FDA is proposing to continue to apply the current general enforcement discretion approach to ‘1976-Type LDTs…[Since many] serological tests developed in a blood center’s immunohematology reference laboratory (IRL) are 1976-type LDTs, [FDA] should continue to apply its current general enforcement discretion to these tests. These tests use manual techniques and are performed by highly trained laboratory personnel under the oversight of a blood center medical director and use licensed reagents.” The laboratory developed tests rule comments also described how, “[these] tests are validated and rigorously quality-controlled, are well-established, and follow standard, published references for immunohematology. These test kits are not sold to any entity and are only utilized by the blood center. The volume of production for these tests does not make them commercially viable for mass marketing. Therefore, these important tests would be unavailable for use if not performed under the current enforcement discretion.”
In the laboratory developed tests rule comments, ABC listed additional examples of necessary tests used by blood centers that would be impacted by the new enforcement approach proposed in the LDT regulation including:
- ABO discrepancy resolution;
- other tests using in-house donor cells;
- tests using anti-sera created from donor plasma;
- flow cytometric analysis; and
- molecular testing.
In urging FDA to apply the same rationale and reasoning used for exempting HLA LDTs for transplantation from the proposed rule, the ABC LDTs rule comments stated that a similar approach should be applied to, “all LDTs in blood centers and to all HLA tests [since such] tests are generally developed, and the testing is generally performed in urgent, life-saving situations for the patient, where a physician must make a prompt decision about the transfusion based on medical judgment regarding their patient’s condition and the degree of mismatch between the donor and patient when performing a blood transfusion.”
ABC concluded the laboratory developed tests rule comments by explaining that, “[u]nless blood centers’ LDTs are fully excluded from FDA’s enforcement approach applied to in vitro diagnostic products (IVDs), there will be significant patient harm due to delays in care and the lack of patient access to medically necessary tests due to the new regulatory burdens. [These] tests are generally developed, and the testing is generally performed in urgent, life-saving situations for the patient, where a physician must make a prompt decision about the transfusion based on medical judgment regarding their patient’s condition and the degree of mismatch between the donor and patient when performing a blood transfusion. If these tests are unavailable, physicians must still make a prompt decision about the transfusion, and they will have less information available to them to determine the safest course of action.” ABC also noted the potential of the proposed LDT regulation to, “exacerbate the impact of the existing laboratory workforce shortage without improving safety. Blood centers would need to hire additional specialized staff and provide training to staff on a new, complicated FDA regulatory scheme. This would come at a time when pathology and laboratory medicine are experiencing extreme workforce challenges. For example, the overall vacancy rate for blood bank immunohematology laboratory departments was 17.8 percent in 2022, with staff vacancy rates at 18.9 percent.” ABC will continue to provide updates regarding the proposed rule.