The Center for Biologics Evaluation and Research (CBER) has just published a new draft guidance document intended to clarify the premarket notification, or 510(k), process for certain types of test kits used to match donors and recipients during transfusions and transplantations.

Background

The test kits in question are known as nucleic acid-based human leukocyte antigen (HLA) test kits, which are used to ensure compatibility between a donor of human cells, tissues, tissue-based products or organs and their eventual host. Non-compatible organs may be rejected by the immune system of the recipient or result in a condition known as graft-versus-host disease in which transplanted immune cells attack the new host.

The guidance comes at a time when the science behind HLA test kits is growing "increasingly complex," FDA observed.

"Testing has evolved from serology and cell-based methods with little instrumentation to deoxyribonucleic acid (DNA) based and multiplex assays that use complex instruments and software," FDA recalled. Regulators also noted the "high degree of polymorphism" and "rare phenotypes" associated with the HLA system, and said they represented "significant and unique challenges" to obtaining regulatory approval.

And those challenges can be amplified by the 510(k) submission system, which relies more on the history of similar devices to prove safety and efficacy than on new data submitted with respect to a new device.

Guidance

FDA's draft guidance, Recommendations for Premarket Notification (510(k)) Submissions for Nucleic Acid-Based Human Leukocyte Antigen Test Kits Used for Matching of Donors and Recipients in Transfusion and Transplantation, makes numerous recommendations to industry.

Among them:

• Specify in the intended use statement on the device's label which specific locus or loci the test is intended to be used with.
• Companies should specify in detail the characteristics of the device, including its test platform, composition, methods of use, assay components, methodology for FDA extraction, and processing limits.
• Performance studies conducted in support of the device "should demonstrate, with a high level of confidence, that the test kit performs within the established specifications." Studies should be conducted to determine accuracy, repeatability and reproducibility, and performance in clinical settings.
• If the HLA test kit utilizes software, that software should be validated per existing FDA guidance and include an assessment of how essential the software is to the functioning of the device
• Test kits of multiple loci may be bundled into a single 510(k) submission, but all required information on each device must be contained within the submission.

FDA will be accepting comments on the guidance until 18 February 2014.

Guidance

Federal Register