Posted: 07 May 2020 07:09 PM PDT
By Sara W. Koblitz —
The Pharmaceutical Manufacturing Research Services (“PMRS”) appears to abide by the proverb “If at first you can’t succeed, try try again.” After several denied Citizen Petitions, striking out in the Eastern District of Pennsylvania, and bringing then dismissing another suit against FDA in that same court, PMRS has tried its hand at influencing FDA’s abuse deterrence policy for opioids in the courts once again. PMRS filed suit against FDA in the D.C. Circuit in December 2018 alleging violations of the Administrative Procedure Act (“APA”) when FDA refused to approve its abuse deterrent oxycodone product. And once again, PMRS lost.
As a quick refresher, PMRS is a contract drug manufacturer that has made a habit of challenging FDA’s approval of abuse-deterrent opioids. Most of its challenges have failed, so PMRS decided to submit to FDA its own New Drug Application (“NDA”) for an immediate-release abuse-deterrent oxycodone formulation containing a dye intended to create a “visual deterrent” to abuse by suggesting that the product was contaminated. FDA refused to approve the NDA, determining that the proposed product labeling was false and misleading because there was no evidence that the product was, in fact, less prone to abuse by patients. Further, there were no abuse-deterrent properties of the formulation itself, meaning that it could not be considered an “abuse-deterrent formulation.” PMRS refused to reformulate the product and insisted that the product had abuse-deterrent dosing instructions. PMRS argued that FDA’s approach to abuse deterrence was “misleading, unscientific, and dangerous” and requested a hearing on the agency’s approach to abuse deterrence more generally. FDA denied this request on the grounds that legal and policy objections have no bearing on the approvability of the NDA. After PMRS requested a hearing, FDA refused to review a labeling resubmission.
PMRS challenged the denial of its NDA approval and FDA’s procedural denials. First, PMRS argued that a false or misleading label is not a sufficient ground to deny approval under the FDC Act. Second, PMRS contended that denying approval of an NDA on the basis of labeling was arbitrary and capricious under the APA. In a decision that is unlikely to surprise anyone, the D.C. Circuit found that the statute does provide FDA the authority to deny an NDA based on false and misleading labeling and that FDA’s denial of NDA approval was not arbitrary and capricious.
The Court first addressed FDA’s authority to deny an NDA based on false or misleading labeling. The Court acknowledged that section 505 of the FDC Act states an “irreconcilable contradiction” in that it states that FDA shall approve an application if none of the grounds for denying approval in subsection (d) applies while subsection (d), containing grounds (1)-(7), states that FDA shall approve an application if grounds (d)(1) through (d)(6) do not apply. Given this inconsistency in the statute, the Court looked to the context. It determined that “the totality of the statutory context confirms that the FDA must deny an application if the label is false or misleading. . . .”
With respect to PRMS’s claim that denial of NDA approval was arbitrary and capricious, the Court looked at whether the decision was reasonable and reasonably explained. In the context of a challenge to the FDA’s decision-making, the Court noted that it gives “a high level of deference” to the agency’s scientific analysis of the evidence before it. FDA explained its reasoning in detail in the Denial Order—even if “not a model of clarity”—and “examined the material factors” and “considered the record as a whole.” Further, FDA gave a rational explanation for its refusal to consider a resubmission with a revision to draft labeling since FDA regulations require an applicant to choose a hearing or a resubmission, and PMRS chose a hearing. In sum, FDA provided a reasonable explanation for its decision to deny PMRS’s application and resubmission, and that’s all the APA requires.
Finally, the Court admonished PMRS for its use of the court system to convince FDA to accept its “preferred approach to abuse deterrence.” Noting that dosing and labeling have nothing to do with abuse deterrent formulation, the Court explained that referring to the product as an “abuse-deterrent formulation” is plainly false and misleading. PMRS provided no evidence to support its claim that its product was an abuse-deterrent formulation and therefore could not remedy the false misleading nature of its labeling. As such, there is no relevant factual dispute providing a basis on which to grant a hearing. Further, FDA regulations clearly state that hearings will not be granted on issues of policy and law under 21 C.F.R. § 12.24(b)(1).
Given PMRS’s litigation track record, this probably isn’t the last FDA or the courts will hear from them.
The Pharmaceutical Manufacturing Research Services (“PMRS”) appears to abide by the proverb “If at first you can’t succeed, try try again.” After several denied Citizen Petitions, striking out in the Eastern District of Pennsylvania, and bringing then dismissing another suit against FDA in that same court, PMRS has tried its hand at influencing FDA’s abuse deterrence policy for opioids in the courts once again. PMRS filed suit against FDA in the D.C. Circuit in December 2018 alleging violations of the Administrative Procedure Act (“APA”) when FDA refused to approve its abuse deterrent oxycodone product. And once again, PMRS lost.
As a quick refresher, PMRS is a contract drug manufacturer that has made a habit of challenging FDA’s approval of abuse-deterrent opioids. Most of its challenges have failed, so PMRS decided to submit to FDA its own New Drug Application (“NDA”) for an immediate-release abuse-deterrent oxycodone formulation containing a dye intended to create a “visual deterrent” to abuse by suggesting that the product was contaminated. FDA refused to approve the NDA, determining that the proposed product labeling was false and misleading because there was no evidence that the product was, in fact, less prone to abuse by patients. Further, there were no abuse-deterrent properties of the formulation itself, meaning that it could not be considered an “abuse-deterrent formulation.” PMRS refused to reformulate the product and insisted that the product had abuse-deterrent dosing instructions. PMRS argued that FDA’s approach to abuse deterrence was “misleading, unscientific, and dangerous” and requested a hearing on the agency’s approach to abuse deterrence more generally. FDA denied this request on the grounds that legal and policy objections have no bearing on the approvability of the NDA. After PMRS requested a hearing, FDA refused to review a labeling resubmission.
PMRS challenged the denial of its NDA approval and FDA’s procedural denials. First, PMRS argued that a false or misleading label is not a sufficient ground to deny approval under the FDC Act. Second, PMRS contended that denying approval of an NDA on the basis of labeling was arbitrary and capricious under the APA. In a decision that is unlikely to surprise anyone, the D.C. Circuit found that the statute does provide FDA the authority to deny an NDA based on false and misleading labeling and that FDA’s denial of NDA approval was not arbitrary and capricious.
The Court first addressed FDA’s authority to deny an NDA based on false or misleading labeling. The Court acknowledged that section 505 of the FDC Act states an “irreconcilable contradiction” in that it states that FDA shall approve an application if none of the grounds for denying approval in subsection (d) applies while subsection (d), containing grounds (1)-(7), states that FDA shall approve an application if grounds (d)(1) through (d)(6) do not apply. Given this inconsistency in the statute, the Court looked to the context. It determined that “the totality of the statutory context confirms that the FDA must deny an application if the label is false or misleading. . . .”
With respect to PRMS’s claim that denial of NDA approval was arbitrary and capricious, the Court looked at whether the decision was reasonable and reasonably explained. In the context of a challenge to the FDA’s decision-making, the Court noted that it gives “a high level of deference” to the agency’s scientific analysis of the evidence before it. FDA explained its reasoning in detail in the Denial Order—even if “not a model of clarity”—and “examined the material factors” and “considered the record as a whole.” Further, FDA gave a rational explanation for its refusal to consider a resubmission with a revision to draft labeling since FDA regulations require an applicant to choose a hearing or a resubmission, and PMRS chose a hearing. In sum, FDA provided a reasonable explanation for its decision to deny PMRS’s application and resubmission, and that’s all the APA requires.
Finally, the Court admonished PMRS for its use of the court system to convince FDA to accept its “preferred approach to abuse deterrence.” Noting that dosing and labeling have nothing to do with abuse deterrent formulation, the Court explained that referring to the product as an “abuse-deterrent formulation” is plainly false and misleading. PMRS provided no evidence to support its claim that its product was an abuse-deterrent formulation and therefore could not remedy the false misleading nature of its labeling. As such, there is no relevant factual dispute providing a basis on which to grant a hearing. Further, FDA regulations clearly state that hearings will not be granted on issues of policy and law under 21 C.F.R. § 12.24(b)(1).
Given PMRS’s litigation track record, this probably isn’t the last FDA or the courts will hear from them.
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