Regulatory Update, November 2016
Proposed Changes to NIH Guidelines for Human Stem Cell Research
In the August 5, 2016 Federal Register, the NIH requested public comment on a proposal to amend Section IV and Section V of the NIH Guidelines for Human Stem Cell Research and on the proposed scope of certain human-animal chimera research that will be considered internally by an NIH steering committee to provide programmatic input to the director of the relevant NIH Institute(s) or Center(s) or equivalent NIH officials responsible for funding decisions. The comment period was extremely brief, ending on September 6, 2016.
Since the NIH Guidelines were issued in 2009, growing knowledge and advancement of stem cell biology has created new research opportunities. Some scientists are exploring strategies for growing human tissue and organs in animals through the introduction of human pluripotent cells into early stage embryos of non-human vertebrate animals. These experimental designs raise questions regarding where the human cells might go in the developing animal and how they might function, such as whether the human cells might contribute to the central nervous system and affect the cognition of the animal.
In 2015, while considering these issues, the NIH issued a funding moratorium. It also held a workshop with experts on November 6, 2015, to review the state of the science and discuss animal welfare issues. The workshop illustrated that while there are significant challenges to creating chimeric models, there is clear interest and potential in producing animal models with human tissues or organs for studying human development, disease pathology and eventually organ transplantation.
The NIH has decided to establish a steering committee to provide input to the relevant NIH Institute(s) or Center(s) on human-animal chimera research proposals. It will consider factors such as (1) the characteristics of the human cells to be introduced (including potency and any modifications of those cells); (2) characteristics of the recipient animal (e.g., species, stage of development, and any modifications that affect location or function of human cells); (3) other data relevant to the likely effects on the animal (e.g., changes in cognition, behavior or physical appearance); (4) planned monitoring (including animal welfare assessments); and (5) any staging of proposed research (e.g., assessing the outcome of a particular experiment before conducting a further experiment). This internal programmatic work will be conducted independent of, and in addition to, the usual peer review procedures for research at the NIH.
The NIH also proposes to revise the Guidelines to expand the existing prohibition on introducing human pluripotent stem cells into blastocyst stage nonhuman primate embryos to include pre-blastocyst stage nonhuman primate embryos; and to expand the prohibition on research involving the breeding of animals where the introduction of human embryonic stem cells or human induced pluripotent stem cells may contribute to the germ line to include any human cells that may result in the formation of human gametes. Interested readers should see the notice for a detailed summary of the proposed changes for which comments are solicited.
FDA Final Guidance on Medical Device Clinical Study Adaptive Designs
In the July 27, 2016 Federal Register, the FDA announced the availability of a final guidance document titled “Adaptive Designs for Medical Device Clinical Studies.” This guidance provides sponsors with guidance on how to plan and implement adaptive designs for clinical studies when used in medical device development programs. An adaptive design for a medical device clinical study is defined as a clinical trial design that allows for prospectively planned modifications based on accumulating study data without undermining the trial’s integrity and validity. Adaptive designs, when properly implemented, can reduce resource requirements and/or increase the chance of study success.
The document provides guidance on how to plan and implement adaptive designs for clinical studies when used in medical device development programs. It addresses adaptive designs for medical device clinical trials and is applicable to all medical device marketing submissions, including investigational device exemption (IDE) submissions. This guidance can be applied throughout the clinical development program of a medical device, from feasibility studies to pivotal clinical trials. It does not apply to clinical studies of combination products or co-development of a pharmaceutical product with an unapproved diagnostic test.
Interested parties may submit electronic or written comments on final guidance at any time. FDA may consider those comments for future revisions. Submit electronic comments at http://www.regulations.gov/. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Room 1061, Rockville, MD 20852. Identify comments with Docket No. FDA-2015-D-1439. The FDA also has instructions on how to submit confidential information. If those instructions are not followed, any submitted confidential information will be made public.
The Regulatory Update is excerpted from Research Practitioner, Volume 17, Number 05, September-October 2016.