Penile Cosmetic Surgery Center

Historically, penile augmentation surgery used free dermal grafts of the patient’s own skin (dermal fat grafts, or DFGs). These grafts were placed on the penis to increase penis girth. Today, a patient can choose to have his penis enlarged with AlloDerm®. AlloDerm is the most up-to-date material for use in penile augmentation surgery. Dr. Alexander Krakovsky is among a select group of physicians who perform penile augmentation surgery using AlloDerm for penile girth augmentation and penile glanular augmentation.

Why AlloDerm?  There are several reasons why a patient might prefer AlloDerm to DFGs. One advantage of AlloDerm over DFGs is that the patient does not need to provide grafts from his own body, thereby avoiding the potential complications and discomfort of additional incisions and the accompanying healing process. A second advantage is the avoidance of unsightly residual scars. A third advantage is that, because the need to take grafts from the patient’s body is eliminated, the time required for the surgical augmentation procedure itself is reduced.

What is AlloDerm? AlloDerm, a product of LifeCell Corporation, is an acellular tissue regeneration matrix. It is what remains after donated human skin (tissue) is processed to remove human cells (acellular)—most notably the epidermal and dermal cells—through a patented method, while preserving and stabilizing the remaining biochemical components and structure (matrix) of the dermis. This resulting framework (comprised of collagen, elastin, protein, hyaloronan, proteoglycans, fibronectin, and vascular channels) is used as a graft to support cellular repopulation and vascularization (regeneration). Put another way, the patient’s body fills the AlloDerm scaffolding with its own blood and cells to create and incorporate new tissue. In phalloplasty surgery, the AlloDerm graft is used to enhance the girth and/or glans of the penis in the male cosmetic surgical procedures described on this website.

How safe is AlloDerm? AlloDerm is regulated by the FDA as a human tissue for transplantation, or as a banked human tissue. The donated human cadaver skin (allograft) from which AlloDerm is derived comes from United States AATB-compliant tissue banks. The allograft is recovered, screened, tested, processed, stored, and distributed in accordance with the standards and guidelines of the American Association of Tissue Banks (AATB); the Food and Drug Administration’s (FDA) applicable CFR (Center for Devices and Radiological Health) regulations and requirements for the procurement and processing of banked human tissue; and any applicable state requirements.

AlloDerm undergoes a strict and comprehensive series of procedures, guided by FDA, AATB, and other standards, to assure its safety. AlloDerm donors are pre-screened and tested for transmissible diseases, and the grafts from which AlloDerm are derived are subsequently obtained at the time of death. Microbiological cultures are performed on each lot to assure the absence of bacterial and fungal pathogens. Once processed, histology and immunohistochemistry are performed on AlloDerm to confirm the presence of an intact basement membrane complex, retention of collagen, and an absence of cells. According to LifeCell Corporation, AlloDerm has been used for more than 1 million implants and grafts with no confirmed cases of viral infectious disease transmission.

What is the difference between FDA-approved and off-label uses of a drug or product?The FDA licenses and approves a drug or product to be safe and effective for each specific type of use (indication) of the product. As the FDA explains:

It is important to recognize that it is never a drug or other product that is approved or not approved, but a claim about the use of the drug or product. The claim is granted a marketing license, which is, in effect, a product label.

These approved uses are “on-label uses,” because the uses (as well as dosage and other details) are listed on the product packaging and in product promotions and advertising. Obtaining this use-specific FDA licensing and approval can be a long and costly process, involving many clinical trials, extensive research, and other requirements to ensure the safety and efficacy of the drug or product for a particular indication.

There may be many other, often related, uses or indications for which the drug or product is beneficial, but for which not enough research evidence or research funding has been gathered, or for which the approval process has not yet been completed or even begun. These uses that have not been approved by the FDA are called “off-label uses.” Eventually, once the FDA licensing and approval process has been completed for an off-label use, that use can be added to the product’s label.

The FDA approves uses of drugs, but does not regulate the practice of medicine. In the words of the FDA’s Center for Drug Evaluation and Research:

Neither the FDA nor the Federal government regulate the practice of medicine. Any approved product may be used by a licensed practitioner for uses other than those stated in the product label. Off-label use is not illegal, but means that the data to support that use have not been independently reviewed by the FDA.

When the FDA approval process is complete for prescription use of a particular drug or product, the drug or product becomes available to the physician for unlisted or off-label use in his or her practice of medicine. FDA regulations permit physicians to prescribe FDA-approved drugs or products for off-label uses, with the exception of certain regulated substances, such as opiates.

Off-label use, that is, use of an FDA-approved drug or medical product for a purpose or indication not listed on the product label, is not only legally acceptable, but even prevalent in the United States, and has been for years. In a 2001 study by Radley, Finkelstein, and Stafford, there were an estimated 150 million off-label prescriptions among the sampled medications. Available research estimates range widely regarding the percentage of drug prescriptions written in the United States for off-label use. This figure is higher for certain groups and for certain drugs. For example, Namjoshi points out that “some 80% of pediatric drug use is off-label” and the GAO, reporting on their study in 1991, stated that: “More than half of the patients (56 percent) were prescribed at least one drug off-label.”

Sometimes the off-label use of a drug or product is the standard of care for a particular indication ; sometimes it represents optimal care ; and it has even been called the “gold standard” in some cases. Some drugs or products are used more for off-label purposes than for their FDA-approved indications ; for some indications, particularly rare diseases, the off-label use of a product is the only remedy available.

Klein and Tabarrok summarize in this way: “Physicians prescribe off-label because medical knowledge advances at a faster rate than the FDA.” Or, as noted in a decision by a Tennessee Appellate Court in 2000: “Because the pace of medical discovery runs ahead of the FDA's regulatory machinery, the off-label use of some drugs is frequently considered to be 'state-of-the-art' treatment.”

In their off-label use of prescription drugs and products, physicians are expected to apply their best professional judgment to ensure safety, effectiveness, and benefit for the patient. According to the USFDA,

Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment. If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence.

What are the FDA-approved and off-label uses of AlloDerm?AlloDerm was originally developed as a skin substitute for burn victims, and it is licensed and approved by the FDA as a skin substitute for transplantation in both medicine and dentistry for various uses. Although LifeCell can only advertise their product as being useful for these FDA-approved purposes, as noted above, it is legal for doctors to use AlloDerm for other applications.

Like many drugs and medical products in the United States, AlloDerm already has quite a number of off-label uses, and this number is growing every day. Uses of AlloDerm include general, dental, orthopedic, urogenital, and plastic reconstructive (breast and abdominal wall reconstruction, and rhinoplasty, for example) surgical procedures. AlloDerm is also being used as a cardiac patch, for repairs of the GI tract, as a dural replacement, and for ventral and other types of hernia.

The use of AlloDerm in phalloplasty augmentation surgery is an off-label use of the product that has now proven successful over a number of years. Off-label use of a product is bolstered by published peer-reviewed articles that provide further information about the product’s off-label use. Dr. Alexander Krakovsky has been one of the first to publish articles that specifically and extensively address the use of AlloDerm in penile augmentation surgery.

More information about AlloDerm can be found at the LifeCell Corporation website. Copies of legal documents related to the regulation and processing of AlloDerm can also be found at this site, including LifeCell’s AATB Accreditation, California Tissue Bank License, and FDA Registration for AlloDerm. Please see the LifeCell website at http://www.LifeCell.com/.

End Notes

1. E.D. Whitehead, Allograft Dermal Matrix Grafts (AlloDerm®), http://www.drwhitehead.com/phallo_allo.html, 1998-2005 (accessed April 1, 2008).
2. LifeCell Corporation, AlloDerm Defined,http://www.lifecell.com/products/95/, 2008 (accessed April 1, 2008).
3. LifeCell Corporation, Patient Information: AlloDerm – A Safe and Effective Alternative to Your Own Tissue,http://www.lifecell.com/products/12/, 2008 (accessed April 1, 2008).
4. LifeCell Corporation, AlloDerm Defined, 2008.
5. LifeCell Corporation, FAQs,http://www.lifecell.com/products/138/, 2008 (accessed April 1, 2008).
6. All About Lip Augmentation!, Human Cadaver-derived Implants, http://www.lipaugmentation.com/bioimplants.htm#AlloDerm, 2001-2006 (accessed April 2, 2008).
7. LifeCell Corporation, Patient Information: AlloDerm – A Safe and Effective Alternative to Your Own Tissue, 2008.
8. Federal Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (USFDA), Oncology Tools: A Short Tour,http://www.fda.gov/cder/cancer/tour.htm, May 2, 2007 (accessed April 2, 2008).
9. Federal Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (USFDA), Oncology Tools: A Short Tour, May 2, 2007.
10. Federal Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (USFDA), Oncology Tools: A Short Tour, May 2, 2007.
11. United States General Accounting Office, Off-label Drugs: Reimbursement Policies Constrain Physicians in Their Choice of Cancer Therapies, GAO Report to the Chairman, Committee on Labor and Human Resources, U.S. Senate, September 27, 1991, pages 5, 27.
12. United States General Accounting Office, Prescription Drugs: Implications of Drug Labeling and Off-Label Use, GAO Testimony Before the Subcommittee on Human Resources and Intergovernmental Relations, Committee on Government Reform and Oversight, U.S. House of Representatives, September 12, 1996, pages 2-3.
13. D.C. Radley, S.N. Finkelstein, and R.S. Stafford, Off-label Prescribing Among Office-Based Physicians, Arch Intern Med, 2006, 166, page 1021.
14. S. Namjoshi, A Primer on: Off-Label Marketing of Pharmaceuticals, Reston, VA: American Medical Student Association, 2005, page 13.
15. United States General Accounting Office, Off-label Drugs: Reimbursement Policies Constrain Physicians in Their Choice of Cancer Therapies, September 27, 1991, page 21.
16. United States General Accounting Office, Off-label Drugs: Reimbursement Policies Constrain Physicians in Their Choice of Cancer Therapies, September 27, 1991, page 11.
17. S. Namjoshi, A Primer on: Off-Label Marketing of Pharmaceuticals, 2005, page 2.
18. United States General Accounting Office, Prescription Drugs: Implications of Drug Labeling and Off-Label Use, September 12, 1996, page 3.
19. D.B. Klein and A. Tabarrok, Who Certifies Off-Label?, Health and Medicine, Summer, 2004, page 60.
20. D.B. Klein and A. Tabarrok, Who Certifies Off-Label?, page 60.
21. D.B. Klein and A. Tabarrok, Who Certifies Off-Label?, page 60.
22. C. Richardson et. al. v. J. Miller et. al., In the Court of Appeals at Nashville, March 1998 Session, Appeal from the Circuit Court for Davidson County, No. 94C-1993, Marietta M. Shipley, Judge, No. M1997-00205-COA-R3-CV – Filed August 16, 2000, footnote 11, page 10.
23. J.M. Beck and E.D. Azari, FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions,Food and Drug L.J., 1998, 53: supra note 70 at page 79.
24. J. Han, The Optimal Scope of FDA Regulation of Genetic Tests: Meeting Challenges and Keeping Promises, Harvard Journal of Law & Technology, Spring, 2007, 20:2, page 437.
25. USFDA (U.S. Food and Drug Administration), “Off-Label" and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices, USFDA Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update, page 1.
26. LifeCell Corporation, Article Abstracts, http://www.lifecell.com/media/70/, 2008 (accessed April 1, 2008).
27. All About Lip Augmentation!, Human Cadaver-derived Implants, 2001-2006.
28. Biohorizons Implant Systems, Inc., AlloDerm Regenerative Tissue Matrix: soft tissue replacement without a palatal harvest , Retrieved March 15, 2008 from http://www.biohorizons.com/documents/alloderm_brochure.pdf, Birmingham: February 2006.
29. Biohorizons Implant Systems, Inc., AlloDerm Regenerative Tissue Matrix: soft tissue replacement without a palatal harvest , February 2006.
30. J.C. Vivian, Off-Label Use of Prescription Drugs, U.S. Pharmacist, http://www.uspharmacist.com, 28:05, posted 5/15/03 (accessed April 4, 2008).
31. Alexander A. Krakovsky, Pubic Liposuction as a Supplement Procedure for Male Enhancement Surgery, World Congress of Liposuction Surgery, St. Louis: October 1-3, 2004, pages 16-17.
32. Alexander Krakovsky, State of the Art in Phalloplasty,The American Journal of Cosmetic Surgery, 2005, 22:3, pages 172-178.
33. Alexander A. Krakovsky, Current Approach to Male Enhancement Surgery: Updated Phalloplasty Technique,Asia Pacific Aesthetic Medicine Journal (APAM), 2007, 1, pages 38-40.
34. Alexander A. Krakovsky, Up-to-Date Surgical Techniques for Penile Augmentation with AlloDerm®, The American Journal of Cosmetic Surgery, Sept 2008,in press.

Bibliography

All About Lip Augmentation! Human Cadaver-derived Implants. http://www.lipaugmentation.com/bioimplants.htm#AlloDerm, 2001-2006 (accessed April 2, 2008).

Beck, J.M. and E.D. Azari. FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions. Food and Drug L.J., 1998, 53, 71-104.

Biohorizons Implant Systems, Inc. AlloDerm Regenerative Tissue Matrix: soft tissue replacement without a palatal harvest . Retrieved March 15, 2008 from http://www.biohorizons.com/documents/alloderm_brochure.pdf, Birmingham: February 2006.

Federal Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (USFDA). Oncology Tools: A Short Tour. http://www.fda.gov/cder/cancer/tour.htm, May 2, 2007 (accessed April 2, 2008).

Han, J. The Optimal Scope of FDA Regulation of Genetic Tests: Meeting Challenges and Keeping Promises. Harvard Journal of Law & Technology, Spring, 2007, 20:2, 423-441.

Klein, D.B. and A. Tabarrok. Who Certifies Off-Label? Health and Medicine, Summer, 2004, 60-63.

Krakovsky, Alexander A. Pubic Liposuction as a Supplement Procedure for Male Enhancement Surgery. World Congress of Liposuction Surgery, St. Louis: October 1-3, 2004.

Krakovsky, Alexander. State of the Art in Phalloplasty. The American Journal of Cosmetic Surgery, 2005, 22:3, 172-178.

Krakovsky, Alexander A. Current Approach to Male Enhancement Surgery: Updated Phalloplasty Technique. Asia Pacific Aesthetic Medicine Journal (APAM), 2007, 1, 38-40.

Krakovsky, Alexander A. Up-to-Date Surgical Techniques for Penile Augmentation with AlloDerm(R). The American Journal of Cosmetic Surgery, Sept 2008, in press.

LifeCell Corporation. AlloDerm Defined. http://www.lifecell.com/products/95/, 2008 (accessed April 1, 2008).

LifeCell Corporation. Article Abstracts.http://www.lifecell.com/media/70/, 2008 (accessed April 1, 2008).

LifeCell Corporation. FAQs.http://www.lifecell.com/products/138/, 2008 (accessed April 1, 2008).

LifeCell Corporation. Patient Information: AlloDerm – A Safe and Effective Alternative to Your Own Tissue. http://www.lifecell.com/products/12/, 2008 (accessed April 1, 2008).

Namjoshi, S.A. Primer on: Off-Label Marketing of Pharmaceuticals. Reston, VA: American Medical Student Association, 2005, 1-31.

Radley, D.C., Finkelstein, S.N. and R.S. Stafford. Off-label Prescribing Among Office-Based Physicians. Arch Intern Med 2006, 166, 1021-1026.

Richardson, C. et. al. v. J. Miller et. al. In the Court of Appeals at Nashville, March 1998 Session, Appeal from the Circuit Court for Davidson County, No. 94C-1993. Marietta M. Shipley, Judge, No. M1997-00205-COA-R3-CV, Filed August 16, 2000, 1-29.

Thomas, P. in response to a question from B. Koshgarian. Quarterly conference call with LifeCell Corporation, Wall Street University.http://siliconinvestor.advfn.com/readmsg.aspx?msgid=22120679, January 1, 2006 (accessed April 5, 2008).

United States General Accounting Office. Off-label Drugs: Reimbursement Policies Constrain Physicians in Their Choice of Cancer Therapies. GAO Report to the Chairman, Committee on Labor and Human Resources, U.S. Senate, September 27, 1991, 1-59

United States General Accounting Office. Prescription Drugs: Implications of Drug Labeling and Off-Label Use. GAO Testimony Before the Subcommittee on Human Resources and Intergovernmental Relations, Committee on Government Reform and Oversight, U.S. House of Representatives, September 12, 1996, 1-8.

USFDA (U.S. Food and Drug Administration). “Off-Label" and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices. USFDA Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update, 1.

Vivian, J.C. Off-Label Use of Prescription Drugs. U.S. Pharmacist, http://www.uspharmacist.com, 28:05, posted 5/15/03 (accessed April 4, 2008).

Whitehead, E.D. Allograft Dermal Matrix Grafts (AlloDerm®).http://www.drwhitehead.com/phallo_allo.html, 1998-2005 (accessed April 1, 2008).