Professional Documents
Culture Documents
Is BioDfactor a stem cell product? NO. BioDfactor is a viable human tissue product. Specifically, BioDfactor is derived from placental tissue that has been cryopreserved to maintain the biologic structure of the collagen that forms the extracellular matrix inherent in the tissue and the viability of the cells naturally present in the placenta. The extracellular matrix provides a natural scaffold for cellular attachment in the body. It is the natural scaffold or micro-scaffold created by the morselized tissue matrix that facilitates the cell migration and proliferation of the patients own cells to achieve the primary function of the product as an in vivo wound covering. The microscaffold is derived from those components essential for fetal growth and development and includes the residual proteins, carbohydrates, hyaluronic acid, growth factors, and other chemical compounds and cells naturally present in the placental tissues and fluid.
1
Copyright
2012
BioPathways/LUXmed.
Confidential
Company
Material.
All
Rights
Reserved.
BioDfence should be promoted as an adhesion barrier to reduce surgical complications associated with scar tissue formation around the dura, nerve endings or surgical hardware. BioDfence is sterile and is resorbed in the body during the healing process. BioDfactor should be promoted as a viable human tissue product. The extracellular matrix formed by the placental collagen provides a natural scaffold for cellular attachment in the body. It is the micro-scaffold created by the morselized tissue matrix that provides the primary function of the product as it covers and protects the wound. In addition to the structural properties of amnion, scientific studies have shown that amniotic fluid contains proteins, hyaluronic acids, cytokines and various growth factors, all of which aid in fetal growth and development. These studies have also shown that amniotic fluid contains multipotent cells that are not only osteogenic, but capable of differentiating into all three germ layers of the human body. While the primary function of BioDfactor is to provide a tissue matrix to cover and protect the wound, the presence of these cells may provide ancillary clinical benefits to the patient. Help me understand the term homologous use in the context of filling bone voids in a spine fusion procedure. One of the four criteria for assessing whether a product qualifies as a Section 361 tissue is whether it is intended for homologous use. Specially, under 21 CFR Part 1271, the term homologous use means the repair, reconstruction, replacement, or supplementation of a recipients cells or tissue with an HCT/P that performs the same basic function or functions in the recipient as in the donor. In the donor, amniotic tissue, fluid and cells function as a biologic system that covers and protects the fetus and aids in fetal growth and development, including the growth and development of bone tissue and the musculoskeletal system of the fetus. In fact, it is the hyaluronic acid, growth factors, proteins, and cells in the amniotic fluid that provides the osteogenic environment that is essential for bone tissue growth in vivo. BioDlogics promotes BioDfactor as a cryopreserved human tissue product. We believe this approach is consistent with other FDA guidance issued in connection with their review of other Section 361 HCT/Ps and supported by the extensive literature assessing the therapeutic application of amniotic fluid and tissue generally. As an example of the broader context in which the FDA has historically interpreted homologous use, in 2001 the FDA acknowledged that amniotic tissue could be marketed for ocular surface wound healing and repair as a Section 361 tissue. We believe the FDA would use a similar approach to the interpretation of the term in any review of BioDfactor. Do I need to be a registered Tissue Bank to distribute BioD products? You do not need to register as a tissue bank if you never take physical possession of the products and, therefore, you are not in the chain-of-custody of the tissue. The intention is to have the products sent directly to the hospital where the clinical procedure is to be performed. If, however, you are in the chain-ofcustody, even to transport the product to the health care facility, then the distributor would be required to also be registered as a tissue bank with the FDA. Remember you do not sell human tissue as that is against the law. You are given a commission for your distribution services. Be sensitive to understanding this especially around the hospital environment. I know a doctor that wants to use BioDlogics products in tendon repair and I have heard of both products being used in different areas of the body. Can I sell it for other clinical applications that meet the homologous use requirement? A physician may use these allografts in
any manner that he sees fit based on his professional judgment and the needs of his patient. You may not promote the products beyond the claims that have been approved by BioDlogics, but you can sell it to him. Officially the agreement between BioDlogics and Amedica is for the spine market.
2
Copyright
2012
BioPathways/LUXmed.
Confidential
Company
Material.
All
Rights
Reserved.
3
Copyright
2012
BioPathways/LUXmed.
Confidential
Company
Material.
All
Rights
Reserved.
Can BioDfence-DryFlex be placed down a tube in an MIS surgery? Yes. The product was specifically designed to allow placement using minimally invasive techniques. The handling characteristics of the dry graft allow it to be pushed down the tube then manipulated by the surgeon for appropriate placement in vivo.
BioDfactor
Why does the brochure say structural matrix when its a liquid? Amniotic tissue is an abundant source of collagen that provides an extracellular matrix to act as a natural scaffold for cellular attachment in the body. Collagen provides a structural tissue matrix that facilitates, among other things, cell migration and proliferation in vivo. BioDfactor was developed using a proprietary technique that morselizes the amnion in an effort to preserve its structural properties in an injectable form. This micro-scaffold created by the morselized tissue matrix is combined with the proteins, carbohydrates, lipids, hyaluronic acid, growth factors, and other chemical compounds naturally present in amniotic fluid and tissue to provide an in vivo wound covering that is derived from those components essential for fetal growth and development. BioDlogics believes that this micro-scaffold provides some structural properties as it covers and protects the wound. Can you explain the antigenic properties of amnion? Immune rejection in the human body occurs when there is a conflict between self and non-self cells that results is immunological conflict. Given the unique function of the placental membrane in the human body, it is believed to produce various immunosuppressive and anti-inflammatory molecules which makes the membrane less susceptible to immunological rejection and, therefore, suitable for use as an in vivo wound covering. The clinical studies and literature often refer to the immunological paradox of pregnancy as the immune privilege of the placental organ due to the low risk of immune rejection. The origin of the immunological conflict is generally known as the Major Histocompatibility Complex (MHC). The MHC is a set of molecules designated as Class I and Class II that are expressed on cell surfaces that trigger immune system defenses, such as an increase in white blood counts or lymphocyte activity. Class I molecules are found on virtually every cell in the human body while Class II molecules are found only on antigenic cells such as B-cells and macrophages. The MHC molecules control the immune response through recognition of self and non-self with those cells identified as non-self targeted for immunologic rejection. Studies have shown that the placental membrane cells do not express MHC Class II antigens which are responsible for the immunologic rejection of allografts in humans. In addition to the absence of MHC Class II molecules, recent scientific research suggests that the placental membrane secretes compounds that may actively cloak the placenta, and the fetus that resides in it, from immunological detection by the maternal cells. To better understand the immune privilege generally associated with amniotic tissue, take a look at the article Immunogenicity of Human Epithelial Cells and Transplantation into Volunteers that can be found on the BioDlogics website. We are not aware of any adverse clinical reactions to products derived from amniotic tissue or fluid that have been processed in a manner similar to BioDfence or BioDfactor. However, as with the implantation of any human tissue there is always some risk of an adverse reaction or immunological response. See the product insert for additional details.
4
Copyright
2012
BioPathways/LUXmed.
Confidential
Company
Material.
All
Rights
Reserved.
What studies have been done to confirm that the cells contained in amniotic fluid generally and BioDfactor specifically are not tumorigenic when implanted in vivo? Dr. Anthony Atala and his team at Wake Forest University School of Medicine and the Wake Forest Institute for Regenerative Medicine have published a number of scientific studies and abstracts related to their research of amniotic fluid stem cell lines. In the article, Isolation of amniotic stem cell lines with potential for therapy, the authors found that the surface marker profile of amniotic fluid-derived stem (AFS) cells and their expression of the transcription factor Oct4 suggests that they represent an intermediate stage between pluripotent embryonic stem cells and lineage-restricted adult stem cells. Unlike embryonic stem cells, they found that AFS cells do not form tumors in vivo. Specifically, they found that none of the four human AFS cell lines tested, including late-passage cells, formed tumors in severe combined immunodeficient mice. In addition to the work at Wake Forest on AFS cells generally, prior to the initial release of BioDfactor, a tumorigenicity study was completed using the product. The study involved 40 nude mice with 20 mice injected subcutaneously with BioDfactor. After 12 weeks, none of the animals developed tumors. The study concluded that BioDfactor is considered non-tumorigenic under the conditions of the assay. Does BioDfactor have Induced Pluripotent Cells? No. Induced means artificially derived. All cells in BioDfactor are naturally present in the placental organ and BioDlogics does not culture, expand, induce or otherwise manipulate any of the cell lines. Why cant we mix BioDfactor with a DBM with glycerol, is it dangerous? No, it is not dangerous, it is NOT a contraindication, but glycerol, depending on the concentration, may be harmful to viable cells. Accordingly, BioDlogics does not recommend use of the product with glycerol. In the end, it is the doctors choice.
AmnioExCel
What is AmnioExCel and how is it used? Unlike BioDfence which acts as an adhesion barrier, AmnioExCel has been developed as an extracellular wound covering that will resorb and incorporate more quickly into the surrounding soft tissue. As such, we believe that AmnioExCel is the ideal choice for filling soft tissue defects. It combines the unique biologic structure of amniotic tissue with the enhanced handling characteristics associated with the DryFlex processing technology. Like BioDfence, AmnioExCel is processed from human amnion.
________________________________________________________________________
5
Copyright
2012
BioPathways/LUXmed.
Confidential
Company
Material.
All
Rights
Reserved.