MYLAN LABORATORIES INC.
May 25, 2006
Dockets Management Branch
Food and Drug Administration
Department of Health and Human Services
Room 1061, HFA-305
5630 Fishers Lane
Rockville, MD 20857
DOCKET NO. 2006P-0123: SUPPLEMENT TO CITIZEN PETITION
On March 16, 2006, Mylan Technologies Inc . ("MTI"), a wholly-owned subsidiary of Mylan Laboratories Inc. ("Mylan"),submitted a Citizen Petition ("Petition") under section 505 of the Federal Food, Drug, and Cosmetic Act and 21 C.F .R. § 10.30. The Petition requested that the Commissioner of the Food and Drug Administration (FDA) require all applicants and holders of approved applications for fentanyl transdermal systems to conduct a study to support the safe and appropriate use of an overlay system with their respective patch.
In this Petition Supplement, submitted under 21 C .F .R. § 10.30(g), Mylan provides evidence from its clinical study that demonstrates that an application of a BioclusiveTM overlay system with the Mylan fentanyl transdermal system does not alter the rate and extent of absorption of fentanyl from the patch. In addition, the study concludes that the use of a Bioclusive overlay system is an effective mechanism to ensure continuous contact between the patch and the skin. See Attachment A for Summary of Study (A copy of the Study in its entirety is simultaneously being submitted by MTI to the Office of Generic Drugs, Bioequivalence Division, for their review.)
As previously noted in the Petition, continuous contact with the skin is necessary for proper drug
delivery from any transdermal product. Disadhesion of a transdermal system may alter the
consistent delivery of therapeutic blood levels in patients who use multiple systems throughout
the course of therapy . Fentanyl transdermal systems are designed for use in patients with chronic pain and therefore the chances of the use of multiple systems is anticipated. As discussed in the Petition, however, the patches may have a problem "sticking" to the skin. Without continuous contact with the skin, the patient may not get the relief from the severe chronic pain, for which the fentanyl patch is prescribed . This has led patients to use untested devices such as athletic tape to ensure continuous contact with the skin. The innovator/distributor of Duragesic(&, Janssen Pharmaceutica Product, L.P ., also recognizes "lack of adhesion" as a problem and offers directly to patients upon request, a Bioclusive overlay system to use on top of its patch.
Although the use of an overlay system can be very effective in making sure that the patch
constantly sticks to the skin, an overlay is also sometimes used to enhance penetration of
transdermally administered drugs . An opioid analgesic such as fentanyl requires very careful use and monitoring as any increase in penetration or damage to the transdermal system, such as the rupturing of a reservoir containing fentanyl system like Duragesic, can lead to a potentially fatal dose of fentanyll . See Duragesic Labeling section entitled "Safety and Handling".
Accordingly, in the interest of public health and safety, Mylan conducted a clinical study to
investigate whether the use of an overlay system with the Mylan fentanyl transdermal system
alters the rate and extent of absorption of fentanyl . The overlay system used by Mylan in the
conduct of this study was Bioclusive, the same overlay system being made available by Janssen to patients having adhesion problems with Duragesic . The results clearly indicate that the Mylan fentanyl transdermal system with a Bioclusive overlay system is bioequivalent to the Mylan fentanyl transdermal system without a Bioclusive overlay. Moreover, the study indicates that continuous adhesion is maintained with the use of a Bioclusive overlay system. By requiring
applicants and holders of approved applications to conduct similar clinical studies, FDA will be
assured that use of a specifically identified and tested overlay system with their respective patch
does not alter drug delivery and can be used as an intervention to overcome "lack of adhesion".
In addition, with the data generated from a study to support the use of an overlay system, FDA
should require all applicants and holders of approved applications to provide information in their
respective labeling that identifies which overlay system was tested and, therefore, considered
appropriate for use. This will ensure that the public, including, physicians prescribing the
product, pharmacists dispensing the product, and patients using the product, have sufficient
information to make an informed decision on the appropriate overlay to be used if a patch does
not stick to the skin. Examples of the type of language that should be added to the labeling to
appropriately inform the public on the correct use of an overlay system for a specific transdermal system is provided in Attachment B.
Sincerely,
John P. O'Donnell
Chief Scientific Officer
