Mylan’s EpiPen Defense Against Generics Focuses On Device Design
This article was originally published in The Pink Sheet Daily
Executive Summary
Mylan wants Teva to conduct comparative studies of its epinephrine auto-injector and to resubmit its ANDA as a 505(b)(2) NDA; citizen petition includes declaration from former FDA advisory committee member.
Mylan Specialty LP contends that Teva Pharmaceuticals USA Inc.’s generic epinephrine auto-injector differs in design and operation from Mylan’s EpiPen and should not be approved until Teva conducts comparative performance tests and is evaluated at a joint meeting of several FDA advisory committees.
In a citizen petition to FDA, Mylan Specialty, a subsidiary of Mylan NV, asks the agency not to approve Teva’s ANDA unless it finds that patients and caregivers can use the generic according to EpiPen instructions and that the differences between the two products do not introduce new risks. It also requests FDA to require Teva to withdraw its ANDA, which references EpiPen, and instead submit a 505(b)(2) NDA.
Mylan says FDA must require Teva to demonstrate that patients and caregivers trained on the EpiPen auto-injector can, without physician intervention or training, safely and effectively use Teva’s proposed generic product in an emergency. Epinephrine auto-injectors are used for emergency treatment of allergic reactions, including potentially fatal anaphylaxis.
“Meeting the burden of proof requires, at a minimum, very carefully designed human factor studies that would demonstrate the Teva product’s safety and effectiveness and its comparability to the EpiPen auto-injector in that regard, as well as technical performance data,” the petition states.
Mylan says such data are beyond the scope of an ANDA and therefore Teva should withdraw the ANDA and resubmit its application as a 505(b)(2) NDA, which allows a sponsor to rely on FDA’s findings of safety and effectiveness for a previously approved drug.
Further, the petition requests that if the product is approved under a 505(b)(2) NDA, FDA not assign it a therapeutic equivalence code indicating its therapeutic equivalence to EpiPen unless the agency finds the two products are bioequivalent and the generic can be expected to have the same clinical effect and safety profile when substituted without retraining.
Approval Standards Raised In Previous Petitions
Mylan’s Jan. 16 petition says that FDA previously established standards for evaluating the approvability of generic epinephrine auto-injectors in its May 2010 response to a citizen petition submitted by Dey Pharma (renamed Mylan Specialty) and in its July 2009 response to a citizen petition submitted by King Pharmaceuticals Inc. (since acquired by Pfizer Inc.).
For example, in its response to the Dey petition, the agency noted that it is important to ensure that patients in an emergency situation can use the generic product safely and effectively in accordance with the instructions provided for the reference listed drug.
Mylan says the Dey petition sought relief with regard to all proposed generic versions of the EpiPen auto-injector and that the agency denied Dey’s request, in large part, because it was categorical and the relevant issues require a case-by-case analysis. Mylan notes that FDA also said it would conduct a product-specific analysis of each proposed generic product that relies on EpiPen as the RLD.
“The Teva ANDA presents a first-of-a-kind, first-in-class medical product, i.e., the first proposed substitutable epinephrine auto-injector, and, more broadly, the first proposed substitutable emergency use auto-injector, presented to the agency,” the petition says.
Product Switch Requires Retraining, Former Advisory Committee Member Says
Mylan’s EpiPen requires users to remove the safety release and then push the tip of the device against the outer thigh. The petition says EpiPen instructions warn users not to touch the needle end of the device.
By contrast, the petition states, Teva’s product, which uses the Vibex auto-injector, has two steps as it requires users to remove a safety cover covering the needle end of the device and to flip a safety clip at the other end before pressing the device into the thigh. The petition also notes that the EpiPen has a higher beginning and ending spring force than the Vibex device.
The petition includes an expert comparative analysis conducted by Interface Analysis Associates which concludes that if Teva’s product is substituted for the EpiPen the use errors that are likely to occur include potential delayed therapy, partial or complete failure to delivery therapy, and possible injury due to unintentional or inverted injection.
The petition also includes a declaration from Eli Meltzer, who was a member of FDA’s Pulmonary-Allergy Drugs Advisory Committee from 1993 to 1995, supporting Mylan’s argument that the two products are significantly different.
Meltzer, of University of California-San Diego School of Medicine, stated that “based on the description of the design and operating principles of the Vibex auto-injector contained in the comparison analysis prepared by Dr. Andre [of Interface Analysis Associates], I do not believe that EpiPen patients could be safely switched to any generic epinephrine auto-injector that utilizes the Vibex platform without retraining by a physician or other healthcare professional.”
Mylan requests that FDA convene a joint meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee, the Pulmonary-Allergy Drugs Advisory Committee, and the General Hospital and Personal Use Devices Panel of the Medical Devices Advisory Committee, to address the issues raised by Teva’s proposed generic version of the EpiPen auto-injector.