Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
J Clin Virol. 2023 Dec;169:105611. doi: 10.1016/j.jcv.2023.105611. Epub 2023 Oct 10.
The 2022 mpox outbreak presented a familiar challenge to clinical laboratories. Accordingly, our institution was able to swiftly implement in-house mpox testing to meet the imminent diagnostic needs of the public health emergency. While the FDA authorized laboratory-developed tests (LDTs) for lesion specimens, however, it restricted the testing of rectal swabs despite mounting evidence of its clinical utility. Notably, within the short timeframe when rectal testing was available, we identified a high-risk patient without apparent lesions who tested monkeypox-positive only by our in-house rectal swab assay. In order for our institution to continue testing non-lesion samples, The FDA required a separate Emergency Use Authorization (EUA) application that demanded additional resource-costly validation studies despite utilizing the same testing platform as lesion samples. Here, we provide a brief review of the history, current status, and legal scope surrounding LDT validations, with an in-depth comparison of the technical requirements by CLIA, CAP and the FDA. Importantly, we provide our experience with the mpox EUA submission process to serve as context for the challenges that may be imposed by the new FDA regulations. We hope that our experience will offer a valuable perspective that promotes constructive discourse towards addressing the imperative to offer high-quality laboratory diagnostics without compromising on the need of the medical laboratory community to provide effective patient care.
2022 年猴痘疫情给临床实验室带来了一个熟悉的挑战。因此，我们机构能够迅速实施内部猴痘检测，以满足公共卫生紧急情况下即将到来的诊断需求。尽管有越来越多的证据表明直肠拭子具有临床实用性，但 FDA 仅授权对皮损样本进行实验室自建检测（LDT），而限制了对直肠拭子的检测。值得注意的是，在可以进行直肠检测的短时间内，我们发现了一名没有明显皮损的高风险患者，仅通过我们内部的直肠拭子检测呈猴痘阳性。为了使我们的机构能够继续检测非皮损样本，FDA 需要单独的紧急使用授权（EUA）申请，尽管与皮损样本使用相同的检测平台，但该申请需要额外资源成本的验证研究。在这里，我们简要回顾了 LDT 验证的历史、现状和法律范围，并深入比较了 CLIA、CAP 和 FDA 的技术要求。重要的是，我们提供了我们在猴痘 EUA 提交过程中的经验，以作为新 FDA 法规可能带来的挑战的背景。我们希望我们的经验将提供一个有价值的视角，促进建设性的对话，以解决提供高质量实验室诊断的紧迫性，同时不影响医学实验室社区提供有效患者护理的需求。
