FDA Sounds Off On Unapproved Ear Drops Through Enforcement Notice
This article was originally published in The Tan Sheet
Executive Summary
FDA says firms marketing unapproved and misbranded prescription otic products containing one or more of antipyrine, benzocaine, chloroxylenol, hydrocortisone, pramoxine and zinc acetate will be subject to enforcement actions including seizure, injunction and/or criminal proceedings.
An infant’s death and the threat that unapproved Rx drugs represent to the OTC monograph process influenced FDA’s decision to enforce against unapproved prescription ear drops, according to the agency.
In a notice prepared for the July 2 Federal Register, FDA said it informed firms marketing unapproved and misbranded prescription otic products containing one or more of the ingredients antipyrine, benzocaine, chloroxylenol, hydrocortisone, pramoxine and zinc acetate that they will be subject to enforcement actions including seizure, injunction and/or criminal proceedings.
The agency did not identify the firms, but said it received at least five adverse event reports of allergic reactions to the unapproved Rx otic products, including angioedema of the ear, eye, face, neck and mouth. Other adverse reactions associated with the products include contact hypersensitivity, pruritus, stinging, burning and irritation.
In addition to safety concerns, the marketing of unapproved drugs presents “direct challenges to the FDA drug approval system and, in some cases, the OTC monograph system.” The targeted products compete with OTC monograph products labeled for cerumen – ear wax – removal and for ear drying.
Additionally, the death of an infant caused by methemoglobinemia – a blood disorder in which an abnormal amount of methemoglobin is produced – was linked to use of a benzocaine otic product, according to the notice.
A spokesman for FDA’s Center for Drug Evaluation said the death was reported in medical literature in 2005. The other adverse events were reports of allergic reactions FDA received through its Medwatch system from 2003 to 2011.
The ear drop enforcement marks another move in an initiative FDA launched in 2003 and strengthened in 2006 with the final guidance, "Marketed Unapproved Drugs - Compliance Policy Guide." The guidance explained that because FDA is unable to take action immediately against all unapproved drugs on the market, it will focus on drugs deemed high priority, under a risk-based approach (Also see "FDA Maps Pathways To Compliance At Unapproved Drugs Workshop" - Pink Sheet, 15 Jan, 2007.).
“As part of the ongoing initiative, a careful recent review by the agency of prescription ear drop (otic) products revealed multiple unapproved versions still being marketed,” the CDER spokesman said.
Homeopathics Stand To Gain
FDA said it expects little to no impact on consumers from the removal of the unapproved products, which frequently are given to young children with ear infections and other conditions that cause ear pain and swelling.
The agency also stated that in addition to safety concerns, the marketing of unapproved drugs presents “direct challenges to the FDA drug approval system and, in some cases, the OTC monograph system.” The targeted products compete with OTC monograph products labeled for cerumen – ear wax – removal and for ear drying.
FDA’s final monograph “Topical Otic Drug Products for Over-the Counter Human Use” permits the use of carbamide peroxide 6.5% formulated in an anhydrous glycerin vehicle as an active ingredient for earwax removal, and isopropyl alcohol 95% in an anhydrous glycerin 5% base as an ear drying aid.
Available OTC carbamide peroxide products indicated for ear wax removal include Prestige Brands Holdings Inc.’s Murine brand and similar private label products offered by retailers.
Homeopathic OTCs, which are not subject to the monograph process, also stand to gain from the agency cracking down on unapproved Rx products indicated for ear problems. Firms marketing homeopathic OTCs to relieve ear problems include Hyland’s Inc. and Similasan Corp.
However, FDA also has made clear it expects homeopathic OTCs to comply with labeling regulations. The agency in 2013 warned three firms that claims for pain and inflammation relief for homeopathic earache products made the products subject to prescription drug regulation (Also see "FDA Warns Homeopathic Earache Products About Rx Claims" - Pink Sheet, 30 Sep, 2013.).
The Mucinex brand OTC guaifenesin-containing expectorant line likely benefitted from the unapproved drug enforcement FDA initiative. After the agency approved an NDA by the brand’s then-marketer Adams Respiratory Therapeutics Inc. to make guaifenesin available OTC in 2002, granting market exclusivity, FDA in 2003 removed unapproved Rx guaifenesin products from the market.
At Mucinex’s OTC launch, Adams – since acquired by RB (Reckitt Benckiser Group PLC) – estimated that 9.4 million prescriptions were being made annually for unapproved guaifenesin products similar to Mucinex, representing around $119 million in lost revenue annually.