In December 2014, FDA published a new Draft Guidance on Minimal Manipulation of HCT/Ps. This Draft Guidance introduced new terminology not found in the regulations and was the apparent basis for the Untitled Letter that MiMedx received over a year earlier related to our micronized products. In October of 2015, FDA further published new Draft Guidance documents related to Homologous Use of HCT/Ps as well as Adipose Tissue. These new Draft Guidances, along with another Draft Guidance of the Same Surgical Procedure Exception, generated such a large outpouring of comments from Industry and the U.S. Congress, that the FDA scheduled public meetings to discuss the draft documents and solicit comments.
The FDA recently held a Public Workshop titled: Scientific Evidence in Development of HCT/Ps Subject to Premarket Approval on September 8, 2016, and held a Public Hearing; Request for Comments on the Draft Guidances Relating to the Regulation of Human Cells, Tissues or Cellular or Tissue-Based Products on September 12-13, 2016.
The FDA’s purpose of the Public Workshop was to identify and discuss scientific considerations and challenges to help inform the development of HCT/Ps subject to premarket approval, including stem cell-based products.
The FDA’s purpose of the Public Hearing was to obtain comments on the four draft guidance documents relating to the regulation of HCT/Ps. For example, the FDA asked for comments on the scope of the four draft guidances, including the particular topics covered, the particular questions posed, whether there are additional issues for which guidance would be helpful, and whether the FDA’s recommendations for each topic are sufficiently clear and consistent within and across documents to provide meaningful guidance to stakeholders. The FDA stated they will consider information it obtains from the public hearing in the finalization of the four draft guidance documents.
While we are encouraged that the FDA agreed to hear input from industry, academia, healthcare practitioners and patients, the Company urged the FDA to reconsider its Draft Guidances on Minimal Manipulation and Homologous Use of HCT/Ps. We were not alone in this respect. As expected, the almost universal sentiment expressed at the September 12-13 hearing from industry and the scientific community was that the Draft Guidances should be amended significantly or withdrawn in their entirety.
Summary of the Majority of Industry, Clinical and Scientific Sentiments Expressed During the Hearing:
Draft Guidances introduced new concepts or proposed changes to the current regulatory scheme, which is inappropriate for guidance. Therefore, Draft Guidances cannot be lawfully adopted in their current form.
Many of the principles in the Draft Guidances are scientifically unsound. Specifically, most presenters objected to the characterization of tissue as either structural or nonstructural, noting that many tissues have multiple functions, both structural and nonstructural.
Multiple objections to the concept that each tissue type has a single “main function.”
Draft Guidances should be amended significantly or withdrawn in their entirety.
If FDA wants to change the way tissue products are regulated, it must do so through a formal notice and comment rulemaking process.
For tissues that don’t currently qualify for regulation under Section 361, many presenters advocated for a new, abbreviated regulatory pathway that would take into account the unparalleled safety record of tissue products and the needs of patients for new and improved products.
Many physicians and patients testified as to the safety and efficacy of HCT/Ps.
MiMedx issued a press release on September 15, 2016 that further describes what we said at the hearing and several other comments from presenters. You can access this press release here.
In an effort to easily direct shareholders to relevant portions of the scientific workshop and to the hearing, we have posted various video clips here. Along with each link is a brief description of each video clip.
Minimal Manipulation & Homologous Use Draft Guidance
Steven R. Bauer, Ph.D., Chief of the Cellular and Tissue Therapy Branch, Division of Cellular and Gene Therapies in the office of Cellular, Tissue and Gene Therapies at the Center for Biologics Evaluation and Research, of the US Food and Drug Administration. Dr. Bauer provided a 30 minute lecture on FDA Perspectives on Scientific Evidence and HCT/P Development. 2 Clips are provided, one in which he states the FDA objective of SAFETY, and one in which he describes High and Low Risk HCT/Ps.
Parker H. “Pete” Petit, Chairman and CEO, MiMedx.
Mr. Petit recommended that the FDA:
Formally withdraw the Guidance Documents on minimal manipulation and homologous use and initiate the formal rulemaking process;
Give industry a reasonable time to comply with any new rules and exercise enforcement discretion on tenured products for companies that enter into and diligently pursue the BLA process.
And, substantively, any new rules:
Should take into account that tissues may have multiple important functions, both structural and non-structural.
Give deference to the proven record of safety and efficacy of human tissues
Provide a scientific basis for conclusions related to new regulations or enforcement action
Please note: Please excuse the distraction caused by a fly that was buzzing the microphone during Mr. Petit’s short 5-minute allotted time slot.
AATB: the AATB is the American Association of Tissue Banks. This video discusses “main” function and notice and comment rulemaking.
Dr. Rebecca Baergen, Professor of Pathology and Laboratory Medicine; Chief of Obstetric and Perinatal pathology and attending pathologist at New York – Presbyterian Hospital, Weill – Cornell Medical Center. Author: Manual of Benirschke and Kaufmann’s Pathology of the Human Placenta. Dr. Baergen summarizes that the in-vivo functions and characteristics of native amnion and chorion are not exclusively structural. She also notes that native amnion and chorion each have several different functions that are derived from the inherent biochemical and cellular compositions of these membranes. It is the position of MiMedx that Dr. Baergen’s presentation clearly illustrated the fact that the FDA’s “main function” argument of HCT/Ps is flawed.
Lisa A. Ferrara, Ph.D., OrthoKinetic Technologies & OrthoKinetic Testing Technologies, is an independent researcher who has conducted Tensile strength testing on EpiFix. Dr. Ferrara concluded that the allograft size does not impact the material properties of dHACM. MiMedx contends that this data illustrates that the argument the FDA made related to the MiMedx Micronized Untitled Letter which claimed that micronization of amniotic tissue resulted in a reduction of tensile strength and elasticity was flawed and incorrect.
Suzanne O’Shea, Navigant Consulting, former FDA employee. Ms. O’Shea recommended the FDA should expressly acknowledge thtat some tissues have both structural and non-structural functionality, among other things.
Paul Kim, Alliance of Wound Care Stakeholders. Dr. Kim speaks about the Minimal Manipulation and Homologous use documents being contradictory to each other, about basic function and main function terminology, and the narrow definition of homologous use in the guidance document.
Karen Ravitz, Esq. – Coalition of Wound Care Manufacturers. Ms. Ravitz contends that the Guidances should provide clarity to the regulations, and should not be adding new requirements to the regulations. Further, she recommends notice and comment rulemaking for substantive changes in regulation.
Jacques Galipeau, MD, Professor of Hematology and Medical Oncology at the University of Wisconsin. Dr. Galipeau explains differences between fresh and frozen Mesenchymal Stem Cells (MSCs), “Stem cells are like sushi – fresh is best.”
Arnold Kaplan, Ph.D., Professor at Case Western University. Dr. Kaplan discusses MSCs.
Michael A. Matthay, MD is a professor of Medicine and Anesthesia at the University of California at San Francisco, and a senior Associate at the Cardiovascular Research Institute. Dr. Matthay explains that Mesenchymal Stem Cells are actually Mesenchymal STROMAL cells.