Derivation of New Human Embryonic Cell Lines in Full Compliance with Current FDA Regulatory Guidance
The research we propose develops improved safety procedures for the establishment of new human embryonic stem cell lines to treat disease. Although it addresses critical safety concerns necessary to move these cells into the realm of human disease treatment, this work could not be funded currently by the federal government. Human embryonic stem cells are used by scientists to study basic questions about biology and how cells and tissues grow. There is also much hope that these same cells will eventually be used also to treat patients. To achieve safety when it becomes possible to use them to treat patients, the collection and handling of cells must be very different from the way the same cells would be handled if they were to be used only for laboratory study. The work we propose is intended to make a complete assessment of safety practices in the way embryonic stem cells are presently handled from the time they are donated to the time they are cultured and frozen for future use. By making this study, we will be able to identify ways to improve safety. We will do this by observing the Food and Drug Administration's regulations for safety in using cells that are intended for use in treating human disease. At the present time, safety procedures are not well developed and it is crucial that they be greatly improved before embryonic stem cells can be used to treat human disease. We believe that these studies will both make stem cells safer to use for people and make such uses for people available more rapidly.
Statement of Benefit to California:
The research we propose is concerned with developing improved safety procedures for the establishment of new human embryonic stem cell lines to treat human disease. Although it addresses critical safety concerns necessary to move these cells into the realm of human disease treatment, this work could not be funded currently by the federal government. When the voters of California approved Proposition 71, they anticipated that research done under its funding would lead to treatment of human diseases and to economic benefits to California's citizenry, although it is understood that much more basic research is also needed before this is to happen. Our work will pave the way for treatment of any human disease using embryonic stem cells by making a detailed and comprehensive study of safety procedures needed for the establishment of new embryonic stem cell lines. The currently approved federal cell lines have both biologic and safety limitations. Therefore, it is critical that new stem cell lines are established in full compliance with existing FDA safety regulations. A method to accomplish this has not yet been devised and we propose to address this barrier to safety and clinical use of human stem cells to treat diseases. This work will benefit California directly because the state will become known as the first to comprehensively address the safety issue. In addressing this issue, the clinical use of stem cells anticipated by Cailfornia's voters will be greatly facilitated while simultaneously being made more safe. In this environment, it will also become more likely that additional biotechnology companies, whose business models will be based on cellular therapy with stem cells, will be established and thrive in the state. these companies will pay taxes and provide employment.
SYNOPSIS: This proposal aims to improve GMP procedures for the isolation of human embryonic stem cells (hESCs), including the consent process and the technical procedure itself. SIGNIFICANCE AND INNOVATION: For hESCS to be useful clinically, it will be important to have GMP procedures that are used for obtaining the blastocyst, the derivation of the cells and the maintenance and banking of the cells. Hence, studies aimed at generating GMP quality hESCs are important. The proposal is not innovative nor terribly significant as it relates to the RFA. The PI proposes to audit current hESC derivation protocols in use by Dr. Susan Fisher, compare these with FDA requirements, and make modifications and recommendations for changes in order for protocols to be more in-line with the FDA. STRENGTH: The only strength is that this project may lead to better compliance with FDA guidelines. WEAKNESSES: Although the goal is important, it is not clear why the investigators approach this question by first surveying the presumed GMP practices, and then making changes. The methodology for obtaining consent, the derivation , expansion and cryopreservation of stem cells should be developed based on knowledge of GMP production of other cells, and implemented. Hence, it is not clear to the reviewers what the investigators hope to gain by the surveillance, and why they do not directly proceed to create consensus guidelines/procedures to be adopted by all "GMP" labs that isolate hESCs. In addition, little attention is given to the degree of differentiation that will be obtained, and how to assure purity of the differentiated progeny, in order to minimize the chance for teratoma formation from the grafted hES-derived cells. The reviewers felt that the proposal was not responsive to the intent of the RFA. The FDA and CFR have already published detailed guidelines for use of human tissue and cell lines. The Center for Biologics Evaluation and Research (CBER) at the FDA regulates human cellular therapy. The FDA is an open, governmental institution and will work with any group planning on deriving or manufacturing cells for therapies. DISCUSSION: There was no further discussion following the reviewers comments.