2-1 provides a summary of the major steps in the anticipated regulatory pathway for the development of a new medical product created using genome editing. The individual steps and considerations listed in this table are discussed in greater detail in the remainder of the chapter. TABLE 2-1 Summary of U.S. Regulatory Pathway for a Medical Product Created Using Genome Editing Step Primary Regulatory Authorities (U.S. System) Examples of Considerations Laboratory research in cells and tissues (nonembryonic), including human induced pluripotent stem cells (iPSCs) · Institutional biosafety committee · Institutional review board (certain uses of human tissue) · NIH-funded researchers must comply with NIH Guidelines for Human Stem Cell Research (certain uses of iPSC lines are prohibited) · NIH-funded researchers must comply with NIH Guidelines for Human Stem Cell Research (only hESC lines approved by NIH may be used; certain uses of hESC lines are prohibited) · Laboratory worker safety · Tissue donor safety, privacy, and rights (human cells and tissue). Adequacy of consent process Laboratory research in human embryonic stem cells or embryos · Institutional embryonic stem cell research oversight or embryo research oversight committees (voluntary but widespread) · Prohibition on use of federal funds for research in which human embryos are created for research purposes, destroyed, or subject to a certain level of risk of harm · Additional state laws as applicable · Special ethical concerns and regulations (federal and state) associated with research using human embryo and hESC lines Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance OVERSIGHT OF HUMAN GENOME EDITING 27 PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION Preclinical animal studies · U.S. Department of Agriculture · Public Health Service Policy on Humane Care and Use of Laboratory Animals · Institutional animal care and use committee · Humane care, study design, and pain minimization Clinical trials (Investigational New Drug [IND] application) · Institutional review board · Institutional biosafety committee · Recombinant DNA Advisory Committee (National Institutes of Health) (advisory) · U.S. Food and Drug Administration (FDA), Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research (CBER) · Balance of anticipated risks and benefits to human subjects · Appropriate protocol design and informed consent New medical product application (Biologic Licensing Application) · FDA CBER · Evaluation of safety and efficacy data Licensed medical product (postmarket measures) · FDA CBER · Long-term patient safety Oversight of Laboratory-Based Research Rules governing research with human cells and tissues, including somatic cells, gametes, embryos, and fetal tissue tend to focus on several key issues. For most cells and tissues, an initial question is whether the donor can receive any kind of payment, in cash or kind. This has been a particularly sensitive issue with respect to gametes used in research, with debate being focused less on the ethics of research using gametes and more on the ethics of how they are obtained and whether it involves anything that resembles undue inducement. For embryos and fetal tissue, rules are influenced by broader legal regimes governing human reproduction and products of conception, to the extent such regimes exist in a given country. And for all tissues, attention is given to whether the tissue is obtained with required permissions from the donor and whether its use poses any risk to the donor’s privacy. These rules can change, of course, when tissue is obtained from cadavers rather than live donors. In the United States, human tissue is donated for research in various ways. Rules governing that donation depend on several factors, the most important of which are whether the tissue is left over from a clinical procedure or is being obtained through a new intervention specifically for research, and whether the resulting tissue specimen has information attached to it that makes the donor’s identity readily ascertainable. When tissue is collected through a physical intervention (such as a blood draw) specifically for research, the donor is a human subject, and an IRB Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 28 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION oversees the recruitment of donors, the procedures used for collection, and the information provided to obtain consent.16 However, as discussed below, merely giving consent to use of already excised tissue does not render the donor a human subject, unless the tissue has information that makes the donor's identity readily ascertainable. Once the tissue has been obtained, it is available for laboratory research, subject to the usual rules for oversight of recombinant DNA research by IBCs. This pattern of regulation is the same regardless of whether genome editing will be carried out on the tissues. Recombinant DNA Research and Institutional Biosafety Committees Research with human tissues and cells that takes place entirely within a laboratory and does not involve either preclinical testing on