FDA Advisory Committee Does Not Support Approval of Opioid with Blue Dye Deterrent

Posted by on November 7, 2017

On July 26th, the FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) to discuss the New Drug Application (NDA 209653) for oxycodone hydrochloride extended-release oral tablets. Oxycodone hydrochloride (HCL) extended-release (ER) oral tablets is an opioid analgesic manufactured by Intellipharmaceutics Corp.  The proposed indication is for management of moderate-to-severe pain where the use of an opioid analgesic is needed for a continuous, extended period. The product has been formulated with properties intended to deter abuse and is available in seven doses: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg. The sponsor requested abuse deterrent labeling only for the IV route of administration, which is believed to be the most dangerous route for abuse.

The committee’s discussions focused on the overall risk-benefit profile of the product, and whether abuse-deterrent properties for their product demonstrated would support labeling. At the end of the day-long meeting, there were 3 discussion questions and 3 voting questions posed to the committee.

The committee was asked whether it was appropriate to consider labelling this product for abuse-deterrent properties for a single route without a complete assessment of all relevant routes of abuse. The totality of data generated from Categories 1, 2, and 3 studies should be used to assess the deterrent effects of opioids to oral and intranasal abuse. The 2015 FDA guidance for industry recommends the submission of studies in all three categories. Intellipharmaceutics Corp submitted Category 1 physical manipulation and chemical extraction studies, but no Category 2 or 3 oral or intranasal human abuse potential studies for the manipulated product. The majority of the committee agreed that it was not appropriate to consider labeling this product with abuse-deterrent properties for a single route without a complete assessment of all relevant routes of abuse. Category 2 and 3 studies provide important information for the evaluation of abuse deterrent formulations with respect to oral and intranasal abuse that cannot be derived from Category 1 studies alone.

The presence of excipients that have been included to deter abuse was also discussed. Oxycodone HCL ER tablets contain a nasal irritant, SLS, and a blue dye, that are intended to deter abuse by the nasal and oral routes. However, no data was provided to support these deterrent claims. Most of the committee agreed that there were concerns regarding the safety and the potential toxicity that may be caused by the excipients. Overall, the committee noted that there has been no assessment for benefit or harm of the blue dye when taken orally or when abused nasally or intravenously, and that there is no evidence of proven deterrent effect of the blue dye. They stated that it was not acceptable to predict intranasal or oral abuse-deterrent effects from Category 1 studies alone for this product and agreed on the need for Category 2 and 3 studies.

The committee voted 4 Yes to 19 No when asked if the applicant demonstrated that the product has properties that can be expected to deter IV abuse. Those voting “yes” said they were strictly addressing the question as written and that the product does have properties that can be expected to deter abuse. Many of those voting against commented that it would be inappropriate to consider labeling this product as having abuse-deterrent properties for a single route of abuse.

There was unanimous agreement that there was not sufficient data to support inclusion of language regarding abuse-deterrent properties in the product’s label for the IV route of administration. Many committee members reiterated the need for category 2 and 3 studies. The majority (No: 22, Yes: 1, Abstain: 0) of the committee agreed Oxycodone HCL ER tablets, should not be approved. The one member who voted “Yes” explained that despite concerns with the blue dye, this drug did not seem any less safe than others currently on the market. The agency is not obligated to follow its committee’s recommendation, but normally does so.

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