Skip to main content

Currently Skimming:

6 Imagining a Potential Clinic Research Pathway for Human IVG in the United States
Pages 79-98

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 79...
... • Based on its regulatory mandate from Congress, FDA would have jurisdiction over IVG, if it progresses into clinical trials or use. However, the current U.S.
From page 80...
... This chapter summarizes perspectives on the elements that could be part of a potential clinical research pathway for IVG in humans and the existing regulatory barriers. These presentations and discussions were held during a panel and a breakout group.
From page 81...
... Bush to the Clinton Administration, NIH established the Human Embryo Research Panel to reevaluate the de facto prohibition on federal funding, Charo said. The panel, on which Charo served, agreed that research using human embryos could be funded in certain 1 Charo noted that, unlike the United Kingdom, no effort was made to create a federal regulatory body focused on ARTs, and such an authority would have been inconsistent with the primarily state-based regulation of medical practice in the United States.
From page 82...
... perform research in which an embryo is destroyed, discarded, or knowingly subject to risk greater than the minimal risk that is allowed for research on fetuses.2 In the amendment, an embryo is defined by how it is made, including by fertilization, parthenogenesis, or cloning, rather than by its biological potential for normal development to term. Charo said that "this now is the background in terms of funding restrictions for the U.S." Embryonic Stem Cell Lines Although the Dickey-Wicker Amendment clearly prohibits using federal funds to derive new ESC lines, as it would destroy embryos, different interpretations allow for federal funding for research on existing ESC lines.
From page 83...
... may be used to notify a sponsor or otherwise acknowledge receipt of a submission for an exemption for investigational use of a drug or biological product … in research in which a human embryo is intentionally created or modified to include a heritable genetic modification. FDA cannot use its money or personnel time or acknowledge receipt of a request to start a trial that creates heritable genetic modifications.
From page 84...
... AN INDUSTRY PERSPECTIVE ON A POTENTIAL PATH TO CLINICAL RESEARCH Krisiloff offered an industry perspective, drawing on his experience as the CEO of Conception Bioscience, a for-profit company developing IVG. He focused his talk on safety requirements that would need to be assessed in preclinical contexts for IVG and potential regulatory frameworks.
From page 85...
... Based on the pace of progress in the field at large, Krisiloff speculated that the first in vitro–derived human gametes could be achieved within the next few years, but these would require years more research and refinement before any potential human clinical trials. Rigorous preclinical research is necessary and would need to encompass in vitro optimization of gamete derivation, quality control development, animal models to test the ability of mammalian in vitro–derived gametes to support successful pregnancies that result in healthy offspring, and safety testing.
From page 86...
... Conversations need to be had to discuss whether other types of animal models would be useful for assessing IVG, he said. Potential Endpoints for Clinical Trials Before IVG ever reaches potential clinical trials, it is important to consider what mechanisms would be used to assess safety.
From page 87...
... Research in both academia and industry relies on private funding to avoid issues related to the Dickey-Wicker Amendment. Last, his view is that IVG does not require genetic modifications to cells and therefore does not contravene the FDA appropriations rider.
From page 88...
... In practice, FDA oversees biologics through rules and regulations derived from these laws, which are interpreted through agency-issued guidance. Appropriations Rider As Charo outlined, the appropriations rider dictates that FDA cannot accept applications for treatments that intentionally create heritable genetic modifications.
From page 89...
... Its rules and regulations ensure that fields are not set back by errors that compromise human safety. Failing to adhere to FDA oversight and the ensuing issues can have a chilling effect on research advances, Marks explained.11 Rigorous preclinical research that establishes safety and efficacy would be key if FDA were ever to consider an IVG application for human use.
From page 90...
... However, the rider was a "product of its time," Marks said, written to block potential clinical uses that would create heritable genetic modifications. A strict interpretation of it as written might enable an application to FDA for IVG, but "there is an excellent chance that at the state and at the federal level, somebody is going to catch on and pass something else that clarifies that this too is not allowed," Charo concluded.
From page 91...
... Greely cautioned that there is not "infinite time" and urged FDA to consider potential pathways for regulating human embryos resulting from technologies soon. Marks agreed, noting that since MRT is likely closer to clinical application in the United States than IVG, learning from its path could help "prepare the way" for IVG if it ever were considered for clinical research.
From page 92...
... Intergenerational Consent Marks discussed informed consent, a key part of any clinical trial that involves giving patients important information, including possible risks and benefits, to help them decide whether they want to take part. As part of follow-up for any first-in-human use of IVG, it would be particularly valuable to track the children conceived for certain medical data.
From page 93...
... Panelists answered and uncovered shared concerns about the United States falling behind if regulatory restrictions are not relieved. IVG as Clinical Innovation Ogbogu asked Marks about whether FDA is anticipating clinicians claiming IVG is a clinical innovation and performing it outside of FDA oversight.
From page 94...
... has advanced MRT to initial clinical trials, and the U.K. political backdrop seems more comfortable with reproductive innovations.
From page 95...
... However, if IVG were combined with a technology such as genome editing of the resulting embryo, then the embryo would also become subject to FDA regulatory authority, many suggested. During the report-out, Glenn Cohen questioned whether regulating the gamete as the product would impact the current interpretation of the appropriations rider.
From page 96...
... Animal Models in Preclinical Research Although standard safety studies could be performed in rodents,15 several participants noted that the proof of concept that IVG creates functional gametes and healthy offspring would need to be shown in a non­human primate model. The proof-of-concept model is important for ­demonstrating feasibility and establishing safety for the resulting baby and 14 Such a system would involve using a nonhuman primate in vitro–derived gamete to create an embryo and then implanting that embryo into a nonhuman primate of the same species.
From page 97...
... Concerns were raised about the feasibility of such multigenerational studies in either model system. Ultimately, one participant noted that laboratory characterization of human IVG and studies in other species, although vital, will not perfectly predict its safety and efficacy for human clinical use and that a decision on whether the evidence was sufficient to permit progress toward human clinical trials would need to be made.
From page 98...
... In the absence of NIH funding and associated standards and oversight, many participants expressed concern that the human embryo research landscape has become a "Wild West." Appropriate oversight and regulation, many noted, would be critical for the ethical advancement of IVG and other reproductive technologies.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.