Knoepfler Paul S
Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, 4303 Tupper Hall, Davis, CA 95616, USA; Genome Center, University of California Davis School of Medicine, 451 Health Sciences Drive, Davis, CA 95616, USA; Institute of Pediatric Regenerative Medicine, Shriners Hospital For Children Northern California, 2425 Stockton Blvd., Sacramento, CA 95817, USA.
Adv Drug Deliv Rev. 2015 Mar;82-83:192-6. doi: 10.1016/j.addr.2014.12.001. Epub 2014 Dec 7.
The phrase "bench-to-bedside" is commonly used to describe the translation of basic discoveries such as those on stem cells to the clinic for therapeutic use in human patients. However, there is a key intermediate step in between the bench and the bedside involving governmental regulatory oversight such as by the Food and Drug Administration (FDA) in the United States (US). Thus, it might be more accurate in most cases to describe the stem cell biological drug development process in this way: from bench to FDA to bedside. The intermediate development and regulatory stage for stem cell-based biological drugs is a multifactorial, continually evolving part of the process of developing a biological drug such as a stem cell-based regenerative medicine product. In some situations, stem cell-related products may not be classified as biological drugs in which case the FDA plays a relatively minor role. However, this middle stage is generally a major element of the process and is often colloquially referred to in an ominous way as "The Valley of Death". This moniker seems appropriate because it is at this point, and in particular in the work that ensues after Phase 1, clinical trials that most drug product development is terminated, often due to lack of funding, diseases being refractory to treatment, or regulatory issues. Not surprisingly, workarounds to deal with or entirely avoid this difficult stage of the process are evolving both inside and outside the domains of official regulatory authorities. In some cases these efforts involve the FDA invoking new mechanisms of accelerating the bench to beside process, but in other cases these new pathways bypass the FDA in part or entirely. Together these rapidly changing stem cell product development and regulatory pathways raise many scientific, ethical, and medical questions. These emerging trends and their potential consequences are reviewed here.
“从实验室到临床应用”这一表述通常用于描述诸如干细胞相关的基础研究成果转化至临床，供人类患者治疗使用的过程。然而，在实验室研究和临床应用之间存在一个关键的中间步骤，涉及政府监管，比如美国食品药品监督管理局（FDA）的监管。因此，在大多数情况下，或许以这样的方式描述干细胞生物药物的研发过程更为准确：从实验室到FDA再到临床应用。基于干细胞的生物药物的中间研发和监管阶段是开发诸如基于干细胞的再生医学产品这类生物药物过程中一个多因素且不断演变的部分。在某些情况下，与干细胞相关的产品可能不被归类为生物药物，在这种情况下，FDA所起的作用相对较小。然而，这个中间阶段通常是该过程的一个主要元素，并且常被通俗地以一种不祥的方式称为“死亡谷”。这个称谓似乎很恰当，因为正是在这个阶段，尤其是在1期临床试验之后的后续工作中，大多数药物产品研发会终止，通常是由于资金短缺、疾病难治或监管问题。不出所料，在官方监管机构领域内外，应对或完全避开这一艰难阶段的变通方法正在不断涌现。在某些情况下，这些努力涉及FDA启用加速从实验室到临床应用过程的新机制，但在其他情况下，这些新途径部分或完全绕过了FDA。这些快速变化的干细胞产品研发和监管途径共同引发了许多科学、伦理和医学问题。在此对这些新出现的趋势及其潜在后果进行综述。
