OKTOS Surgical Corp
June 23, 2005
Mr. Erich Zieler
OKTOS Surgical Corporation
3151 Airway Avenue
Suite I - 1
Costa Mesa, CA 92626
Re: AmbioDry Amniotic Membrane Tissue Grafts
Dear Mr. Zieler:
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed your internet website http://www.oktoophtho.com for the AmbioDry Amniotic Membrane Tissue Grafts (AmbioDry). Copies of the pertinent Internet website pages are enclosed for your reference.
Dehydrated, decellularized amniotic membrane, such as AmbioDry, is a human cell, tissue, or cellular or tissue-based product (HCT/P) regulated under section 361 of the Public Health Service Act (PHSA) and 21 CFR Parts 1270 and 1271, as long as it complies with the criteria in 21 CFR 1270.10(a). One of these criteria is that the HCT/P be minimally manipulated (21 CFR 1271.10(a)(1)), which is defined for cells and nonstructural tissues as "processing that does not alter the original relevant biological characteristics of cells or tissues" (21 CFR 1271.3(f)(2)). A characteristic is "original" if it is present in the tissue in the donor. A characteristic is "relevant" if it could have a meaningful bearing on how the original tissue performs. We have concluded that dehydration and decellularization of amniotic membrane constitute minimal manipulation when the amniotic membrane is used as a wound covering. Such manipulations do not alter the original characteristics of the HCT/P in a way that could have a meaningful bearing on how the HCT/P performs as a wound covering.
However, your website describes AmbioDry's use for wound repair and wound healing, uses that are based on complex interactions between the wound and the product, which actively mediates the healing process through the action of biologically active proteins produced by the cells that reside in this tissue. Examples from your website of wound repair and wound healing claims for your product include:
- "The proprietary AmbioDry tissue process removes the cellular components within the tissue to allow for healthy host revascularization and normal healing integration within the patient's body."
- "The recent availability of AmbioDry Deyhdrated (sic) Amniotic Membrane Allografts for pterygium surgery has provided surgeons with better results that (sic) traditional therapies." Pterygium surgery involves reepithelialization, a process that is actively mediated by cellular factors.
- "Our main goal with the AmbioDry technology has been, and continues to be, to replace the time consuming techniques traditionally employed by ophthalmologists for the treatment of pterygium," stated Erich Ziegler, President of OKTO Ophtho."
FDA has recognized that amniotic membrane that has not been dehydrated or decellularized may be used for wound repair and wound healing. However, the dehydration and decellularization of AmbioDry alters the characteristics of the original amniotic tissue in a way that could have a meaningful bearing on how the HCT/P performs when used for wound repair or wound healing. More specifically, based on a review of the published literature and other data available to the agency, FDA has concluded that removal of cytokine containing cells from this tissue would interfere with human amniotic membrane's ability to actively mediate wound repair and wound healing. Therefore, when intended for these uses, AmbioDry is more than minimally manipulated and does not meet the criteria in 21 CFR 1271.10(a)(1) for regulation solely under section 361 of the PHSA and 21 CFR Parts 1270 and 1271. The wound repair and wound healing claims described in your website require a pre-market application or notification before the product may be legally marketed.
We also note that the articles listed on the "References" page of your website raise concerns which we would like to discuss with you. To the extent that these articles describe wound healing and wound repair uses of amniotic membrane that is minimally manipulated, the articles have very limited relevance to AmbioDry, which is more than minimally manipulated.
AmbioDry may continue to be regulated under Section 361 of the Public Health Service Act and 21 CFR Part 1270 and 1271 as a 361 HCT/P only if all materials are revised to indicate that this product is only intended for wound covering. Please submit a written response to this letter within 10 business days of the date of this letter, describing your intent to comply with this request, listing all materials for AmbioDry that contain claims the same as or similar to those described above, and explaining your plan for discontinuing use of such materials.
Please direct your response to Mr. Glenn N. Byrd, Chief, APLB, at the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448, facsimile 301-827-3528. We remind you that only written communications are considered official responses.
If you choose to revise your materials, APLB is willing to assist you in assuring that your revised materials comply with applicable statutes and regulations by reviewing your revisions before you use them.
----- signature -----
Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research