FDA Issues May Hinder Anti-abuse Opioids: Tufts
Although FDA encourages development of abuse-deterrent formulations (ADF) for opioid drugs, lack of a consistent regulatory policy may hinder innovation in the area, according to a roundtable of pharmaceutical experts convened by the Tufts Center for the Study of Drug Development. The experts’ assessment of the clinical development, regulatory, and reimbursement challenges facing ADF product development are reported in the center’s July/August Impact Report (subscription or purchase required).
The report says that FDA has adopted a flexible, adaptive approach to evaluating and labeling abuse-deterrent products and has identified four categories of studies to comprehensively evaluate ADFs to establish approvability and labeling claims. But, it says, there is a lack of regulatory consistency about demonstrations needed to support labeling of abuse claims and lack of clarity regarding eligibility for three-year data exclusivity for ADF products.
Of the 10 ADF products approved by FDA, four have been launched, Tufts says. The 10 products include nine extended-release formulations and one immediate-release formulation. The report notes that while the focus of ADF development has been primarily on extended-release products, they are the formulations that hold a greater attraction for abusers due to higher per-dose levels of active ingredient.
As of May, there were 25-30 NDAs pending for ADF products. The experts say the three biggest clinical development challenges facing ADF opioids relate to approvals of prodrugs or new molecular entities that can be designed to be resistant to crushing or dissolving, approvals of agents that protect against oral abuse, and approvals of immediate-release ADFs. To date, they say, there are no approved prodrugs or approved agents protecting against oral abuse.
The analysis found that 96% of all opioid products prescribed in the U.S. in 2015 lacked ADF properties. Only 2% of generic opioids prescribed in the U.S. that year contained abuse-deterrent properties, compared with 36% of branded opioids. “The challenge for prescribers and payers is to increase the appropriate uptake of both branded and generic ADFs to reduce the likelihood of abuse,” the report says.
The report concludes that developers, regulators, and payers all hold keys to improving access to ADF products. “Drug developers face considerable challenges regarding prodrug and oral abuse deterrent development,” the experts say. “Prodrugs are new molecular entities, which make them inherently more difficult to develop. Protecting against oral abuse presents a unique problem, as swallowing pills is generally how patients take pain medications. While it is important to demonstrate the clinical effectiveness of new ADF products, post-approval studies take time to generate, and this delay between approval and reimbursement can impede patient access.”