International Society for Stem Cell Research Finally Releases Guidance Document for Clinical Translation of Stem Cells

By: Brett A. Hoover [Follow me on Twitter and LinkedIn]

On Dec. 3^rd, 2008, the International Society for Stem Cell Research (ISSCR) released its long awaited document on the Guidelines for the Clinical Translation of Stem Cells. This document is a first step towards establishing the much needed regulatory standards missing from the Stem Cell and Cellular Therapies industry. Guidelines, in essence, are recommendations founded on general principles. In this case, said guidelines are established by both academic and industrial professionals whose collective experience on the subject matter is unquestionably comprehensive. The following is a summary of the recommendations offered by ISSCR as they pertain to thee particular areas of translational stem cell research: 1) cell processing and manufacture; 2) preclinical studies; and 3) clinical research. It is these thee areas that will be the focus of today’s entry. For brevity, some of the less intriguing recommendations have been omitted:

Cell Processing and Manufacture

Recommendation 5: In the course of development of stem cell-based products, it is imperative to validate surrogate markers of the identity and potency of cell products.

Recommendation 7: Acknowledging the limitations in current assays, scientists and regulators must work together to develop common reference standards for minimally acceptable changes during cell culture, to ensure quality and safety of cell therapy, and to facilitate comparisons across studies.

Recommendation 9: To facilitate international collaboration and universal access to stem cell-based treatments (both during clinical trials and when established as standards of clinical care), there is a need to develop appropriate quality management systems for donation, procurement, testing, coding, processing, preservation of stem cell potency, storage, and distribution of the cells. For extensively manipulated stem cells (either autologous or allogeneic) destined to clinical application, the ISSCR recommends adherence to GMP procedures, which includes minimizing risks to patients from unwanted cell products.

Pre-Clinical Studies

Recommendation 15: The need for studies in non-human primates should be evaluated on a case-by-case basis, and performed only if the studies promise to provide necessary and otherwise unobtainable information for experimental therapeutic application of stem cells or their progeny in patients. All studies involving the use of non-human primates must be conducted under the close supervision of qualified veterinary personnel with expertise in their care and their unique environmental needs.

Recommendation 17: Criteria for release of cells for transfer to patients must be designed to minimize risk from culture-acquired abnormalities.

Recommendation 18: Risks for tumorigenicity must be assessed for any stem cell-based product, especially when extensively manipulated in culture or when genetically modified. A clear plan to assess the risks of tumorigenicity for any cell product must be implemented under the direction of an independent review body prior to approval for human clinical use.

Clinical Research

Recommendation 23: The peer review process for stem cell-based clinical trials should have appropriate expertise to evaluate (a) the in vitro and in vivo preclinical studies that form the basis for proceeding to a clinical trial and (b) the scientific underpinnings of the trial protocol, the adequacy of planned end-points of analysis, statistical considerations, and disease-specific issues related to human subject protection.

Recommendation 25: As a general principle, a stem cell-based approach must aim at being clinically competitive or superior to existing therapies. If an efficacious therapy already exists, the risks associated with a stem cell-based approach must be low and the stem cell-based approach must offer a potential advantage (for example, better functional outcome; single procedure (cell administration) versus life-long drug therapy with associated side effects; reduction in long-term cost).

Recommendation 26: Clinical research should compare new stem cell-based therapies against the best medical therapy currently available to the local population.

Recommendation 31: To advance scientific understanding, research subjects should be asked, in the event of death, for consent to the performance of a partial or complete autopsy to obtain information about the extent of cellular implantation and its morphological and functional consequences. Any request for an autopsy must consider cultural and familial sensitivities.

Recommendation 33: Researchers should publish both positive and negative results and adverse events. To ensure the integrity of scientific information and to promote the highest standards of professional conduct, researchers should present their results at professional scientific conferences or in peer-reviewed scientific journals before reporting their research to the lay media or to patient advocacy groups and associations.

We’re a long way from realizing the full potential of stem cells…at least a decade away from a widely accepted stem cell-based therapeutic to treat a non-quality-of-life disease. Regardless, developing regulatory standards now is critical to long-term success. Should a patient lose their life on account of a stem cell therapy (Clinical Trials or Open Market), the set-back would be monumentally devastating to the industry as a whole.

Slainte Mhath!