Noven Strikes Out Second Time With Transdermal Patch Citizen Petition
This article was originally published in The Pink Sheet Daily
Executive Summary
FDA says ANDA sponsors do not need to conduct real-world usability studies for generic transdermal patch drugs nor conduct adhesion studies in children.
A real-world usability study is not necessary to show that a generic transdermal patch drug has similar adhesion, skin sensitization and irritation effects as the reference listed drug, FDA reiterated in denying Noven Pharmaceuticals Inc.’s second citizen petition.
Noven asked FDA not to approve any ANDA for generic versions of its transdermal attention deficit hyperactivity disorder drug Daytrana (methylphenidate) unless the applicant conducted a usability study in adults, adolescents and children. The company submitted the petition in December after the agency denied a 2012 petition. In denying the first petition FDA said current Daytrana labeling already contains considerable information on usability and it would expect the labeling for generic products referencing Daytrana to contain the same information.
Noven tried to get FDA to change its position based on concerns the agency raised about the adhesion of Noven’s investigational methylphenidate patch. The agency told the company that a detached patch has the potential to adhere to another child. It also said that in vitro adhesive studies do not negate the need to conduct usability studies and such studies should be conducted under real-world conditions.
The company said the agency did not consider these safety and efficacy concerns when denying its 2012 petition (Also see "Noven: Our Patch Problems Should Be Everyone’s Patch Problems" - Pink Sheet, 18 Mar, 2014.).
In a May 20 letter to Noven, FDA Center for Drug Evaluation and Research Director Janet Woodcock said Noven’s suggestion that FDA did not consider these issues in its response “reflects a misunderstanding of how safety and effectiveness are established for a drug approved under an ANDA.”
“For an NDA transdermal patch drug, FDA may seek a usability study to demonstrate that the proposed product is safe and effective when used in real world conditions,” she stated. “Once that demonstration is made for the RLD [reference listed drug] in the NDA, an ANDA applicant relies on the previous finding of safety and efficacy of the RLD and must demonstrate that its product is bioequivalent to the RLD, has similar adhesion, skin sensitization and irritation effects, and is labeled in the same way. A usability study is not necessary to make that demonstration.”
ANDA Sponsors Do Not Need To Conduct Adhesion Study In Children
Noven had sought stricter requirements for ANDA sponsors than those in FDA’s 2010 draft guidance on methylphenidate. Woodcock said the agency disagreed with Noven’s claim that the adhesion study design in the guidance is inadequate to assess adhesion of methylpenidate, even though the guidance recommends that the adhesion study be conducted in adults and the product is indicated for use in children and adolescents. She said the agency is unaware of a significant difference in the adhesion of Daytrana in adults compared with children or adolescents, or of any studies that demonstrate the adhesion of a transdermal product is significantly different based on age.
“Therefore, considering the risk to children as test subjects, and in the absence of a compelling necessity to test adhesion in children as opposed to adults, adhesion studies in children currently are not recommended for any ANDA submissions,” Woodcock stated. “This may be in contrast to the requirements for an NDA, for which it may be appropriate to demonstrate whether relevant real-world differences exist among populations of different ages.”
Noven has two composition and method of use patents on methylphenidate that expire on Sept. 30 2018. A patent on the drug’s transdermal delivery system expires on Oct. 7, 2025. Daytrana had net sales of approximately $61 million in 2013.