May 12, 2006
Bruce S. Lamb, Ph.D.
Senior Vice President, Regulatory Affairs and Quality
One Millennium Way
Branchburg , NJ 08876
Re: LifeCell Corporation and Wright Medical Group - GRAFTJACKET®
Dear Dr. Lamb:
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed the Internet website http://www.wmt.com/graftjacket for GRAFTJACKET® Matrix, GRAFTJACKET® XPRESS Scaffold and GRAFTJACKET Ulcer Repair Matrix. GRAFTJACKET is manufactured and listed with the FDA by both LifeCell Corporation and Wright Medical Group, Inc. (Wright Medical Technology, Inc.) Copies of the website are enclosed for your reference.
GRAFTJACKET® is made from human donor skin, which undergoes a process that removes the epidermis and dermal cells, thereby creating an acellular dermis. Human cells or tissues intended for implantation, transplantation, infusion, or transfer into a human recipient are regulated as human cell, tissue, and cellular and tissue-based products (HCT/P) under Section 361 of the Public Health Service Act (PHSA) and 21 CFR Parts 1270 and 1271, as long as they comply with the criteria in 21 CFR 1271.10(a). Under section 1271.10(a), a product regulated solely as an HCT/P must be minimally manipulated, intended for homologous use only, and not combined with another article, and must not have a systemic effect. This letter focuses on the minimal manipulation criterion.
Minimal manipulation is defined for cells and nonstructural tissues as "processing that does not alter the relevant biological characteristics of cells or tissues" (21 CFR 1271.3(f)(2)). A characteristic is "relevant" if it could have a meaningful bearing on how the tissue performs. Decellularization of dermis constitutes minimal manipulation when the acellular dermis is used as a wound covering. Such manipulations do not alter the original relevant characteristics of the HCT/P in a way that could have a meaningful bearing on how the HCT/P performs as a wound covering. Therefore, if GRAFTJACKET® is marketed as an HCT/P for wound covering only, it is regulated as a "361" HCT/P.
However, the website describes use of GRAFTJACKET® for wound repair and 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 cells that reside in the tissue. The decellularization process alters the characteristics of the original skin in a way that could have a meaningful bearing on how the HCT/P performs when used for wound repair or wound healing. Therefore, the skin has been more than minimally manipulated when promoted for repair or healing of diabetic foot ulcers.
Examples from the website of problematic claims for repair and healing of diabetic foot ulcers include:
- "In fact, clinical data currently submitted for publication shows that treatment with the GRAFTJACKET® matrix is 85% effective, compared to 5% effectiveness for conventional treatment. With the innovative approach of Wright GRAFTJACKET® matrix, physicians and their patients have the potential benefits faster, less costly wound repair- the right results for treating diabetic foot ulcers."
- "Studies show that GRAFTJACKET® Matrix aids in repair of deep wounds with only one application."
- "How GRAFTJACKET® Ulcer Repair Matrix Works... GRAFTJACKET® matrix, when implanted, does several things. The goal is to help repair the foot sore as quickly as possible. Doing so will help prevent infection and possible amputation. GRAFTJACKET® matrix is an important new advance in foot care."
"Building Blocks for Repair ... GRAFTJACKET® matrix is actually a collection of preserved 'bio-building blocks' for repair." "... can often be repaired if given a few essential building blocks."
"Another important aspect of the GRAFTJACKET® matrix is that it is readily revascularized. This means that new blood vessels gain access through preserved blood vessel channels and, essentially, turn the GRAFTJACKET® matrix into living tissue. Lastly, all the components that are in the GRAFTJACKET® matrix are preserved in the biologic state. This means that the body can use these components to help repair itself."
- " How long will it take my wound to heal after GRAFTJACKET® matrix is applied? Between 5-7 days after your surgery, the GRAFTJACKET® matrix starts to incorporate into your body. Normally, complete healing will depend on many factors."
We are concerned that the website contains various claims above and beyond those for wound covering of diabetic foot ulcers. As explained above, we would consider GRAFTJACKET to be more than minimally manipulated, when promoted for wound repair or wound healing, and therefore, it would not meet all of the criteria for regulation solely under section 361 of the PHS Act and 21 CFR parts 1270 and 1271.
GRAFTJACKET® may continue to be regulated solely under Section 361 of the Public Health Service Act and 21 CFR Part 1270 and 1271 as a "361" HCT/P if the website and other promotional materials are revised to indicate that this product is only intended for wound covering. You should specifically delete references to biological activity, healing, and active repair. In addition, the term "repair" should be removed from the proprietary name of the product. If you do wish to make these claims, please contact us so that we may advise you on filing the appropriate pre-market application for the product.
Please submit a written response to this letter describing your intent to comply with this request, and explaining your plan for discontinuing such claims.
Please direct your response to Robert A. Sausville, 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. Should you have any questions or concerns involving this matter, please contact Nancy Chamberlin, Pharm.D, Regulatory Review Officer at 301-827-3028.
If you choose to revise your materials, we are willing to assist you in assuring that your revised materials comply with applicable statutes and regulations by reviewing your revisions before you use them.
Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
Cc: Wright Medical Technology, Inc.
5677 Airline Road
Arlington, TN 38002