We shouldn’t be surprised: the specters of ghosting agency scientific and technical determinations have been wafting about for some time:
- In Alliance for Hippocratic Medicine v. FDA (the Mifepristone “abortion-drug case”), among the issues to be considered by the Supreme Court is whether the petitioners have standing to challenge the FDA’s actions on approving abortion pill, whether the agency’s actions easing restrictions on its conditions of use were arbitrary and capricious, and whether the district court's order suspending the effective date of FDA's actions was improper.
- In Roman Catholic Diocese v. Cuomo, the Supreme Court overturned state Board of Health rulings on social distancing during COVID if religious rights are threatened.
Now, two cases seek to overturn Chevron and, in so doing, dishonor the time-venerated deference to administrative expertise and research resources.
Califf commented that until fairly recently, courts yielded to the FDA as a science-based agency. He worries that Courts will not have the knowledge-based wherewithal to make science-based decisions should Chevron be neutered
“Judges are obviously not scientists and not trained to adjudicate clinical outcome data or biomarker data to make these kinds of decisions….But recently, more judges have stepped in and, … acted like they were FDA.”
- Robert Califf, FDA Commissioner
Califf is concerned that reversing Chevron will not only interfere with or entirely impede the FDA drug approval process, but will invite litigation from companies where FDA decisions are adverse to their interests. Some argue that FDA decisions will be delayed as the FDA spends more time justifying its decisions in preparation for these actions.
While the Supreme Court seems poised to address the Mifepristone case judiciously, that doesn’t provide reassurance that future lower court rulings, like the Fifth Circuit decision leading up to the Supreme Court review, might go rogue.
As the FDA noted in its brief:
“To the government’s knowledge, this case marks the first time any court has restricted access to an FDA-approved drug by second-guessing FDA’s expert judgment about the conditions required to assure that drug's safe use…. through a series of errors that contradict this Court’s precedents and violate black-letter … administrative-law principles.”
And Don’t Even Think About Being Funny
A Chevron reversal would allow courts to assert their judicial (aka political) views on scientific/technical matters, squelching FDA guidance on cutting-edge concerns and technical concerns and interfering with technical decisions from similar agencies like the EPA or NOAA.
Even light-hearted medical guidance by the FDA has provoked judicial ire. Amidst the flourishing of ivermectin use during COVID’s heyday, the FDA and the Department of Health and Human Services sought to discourage the prescription of the veterinary antimalarial drug. Besides concern over effectiveness, the FDA worried about the depletion of the drug for its intended target population – livestock. The FDA posted to social media:
“You are not a horse. You are not a cow. Seriously, y’all. Stop it.”
The post linked to a consumer update noting reports of patients who required medical attention, including hospitalization, after self-medicating with the veterinary product.
Three doctors sued, claiming the FDA’s messaging interfered with medical practice and that the posts violated the Administrative Procedure Act. The Fifth Circuit in Apter v. HHS reversed the lower court ruling, remanding the initial dismissal for further proceedings - but not before ruling that while the FDA “has the authority to inform, announce, and apprise” it did not have the right to endorse, denounce, or advise.” [emphasis added].
Further proceedings have been sealed, so the last word on the subject indicates that judges may forestall FDA advice, even if done in a light-hearted manner.
Orphan Drug Development and the Judicial “Busy-body”
Chevron throws another wrinkle into the decision-making process. The case holds that where a statute act is ambiguous, courts must defer to the Agency charged with its enforcement for interpretation. But often, big bucks are involved, as well as technical concerns. Sometimes, as with the cases before the Supreme Court, economics are the drivers - and insistence on technical or scientific interpretation of statutory language is pedantic. But other times, scientific or medical understanding may matter – at least to those relying on agency practice and policy.
Take the Orphan Drug Act (ODA) of 1982, [1] enacted to encourage pharmaceuticals to develop drugs for rare diseases. In essence, the Act grants a manufacturer a temporary monopoly (“exclusivity”) and other benefits to induce companies to bear development costs for diseases affecting less than 200,000 people.
One such condition is Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune disease affecting adults and children, characterized by fluctuating muscle weakness and autonomic dysfunction, and frequently associated with small-cell lung cancer (SCLC).
Two drug companies entered the “horse race” to obtain FDA approval for their drug candidates. Catalyst Pharmaceutical Co. was the first to cross the FDA- marketing-approval finishing line, and its drug Firadapse was granted Orphan Drug Exclusivity (ODE) for treatment of adult-onset LEMS in 2019. Consequently, competitor Jacobus Pharmaceutical’s drug, Ruguzi, was denied ODE approval. But, Jacobson submitted a new request for the pediatric market, even though the clinical trials submitted were not developed to test that population.
Here, the FDA split the bonanza granting ODE approval to Ruzurgi for treating LEMS in pediatric patients 6 to less than 17 years of age, perhaps motivated by policy concerns or reportedly caving to political pressure.
Not unexpectedly, Catalyst sued.
Legal resolution of the issue depends on the arguably ambiguous statutory wording. FDA policy had been consistent and clear: The statute directs the FDA not to approve a competitor application for the “same drug for the same disease or condition,” but the FDA historically limited its approvals to “indication or use” (e.g., drugs for adults or drugs for children were separate indications, granted separate exclusivities.
Using “indications for use” as a predicate for ODE approval is considered a narrower construction than the statutory language of “disease or condition.” Catalyst challenged the narrower interpretation and claimed the statutory language was clear. On appeal, in Catalyst Pharms v. Becerra, the 11th Circuit agreed, finding that the Orphan Drug Act (ODA) language was not ambiguous and provided for “disease-specific” exclusivity, not the narrower “indications for use.” In so doing, it denied Jacobson’s claim that FDA determination should be afforded deference.
The FDA responded in a rather schizoid fashion, signaling its displeasure. While setting aside its approval of Ruzurgi (as ordered by the 11th Circuit), the FDA declined to adopt the Catalyst ruling across the board and announced it would continue to tie exclusivity to the uses or indications for which a drug was approved, citing expectations in the market-place and the impact on future drug development.
“The FDA expects that the statutory interpretation adopted in the Catalyst decision would affect the incentives for research and development of medical products for rare diseases.”
Perhaps the most significant problem is the uncertainty now surrounding the FDA’s decision-making for orphan drug sponsors. This matter is sure to be exacerbated if Chevron is eviscerated.
“[Reversing Chevron] significantly undercuts FDA’s indication-specific view of orphan exclusivity in favor of a broader approach….”
- George O’Brien, partner Mayer, Brown
While the purpose of the ODA was to encourage drug development, uncertainty in the application and statutory construction torpedoes such incentives. Should Chevron be entirely dismantled, each case will stand on its own, with disgruntled manufacturers seeking to undermine FDA rulings by racing to a court unschooled in science. The cost might just be too much for the market – and patients to bear.
The legislature giveth and the courts taketh away.
[1] “The Orphan Drug Act - Amends the Federal Food, Drug, and Cosmetic Act to allow sponsors of a drug for a rare disease or condition (orphan drug) to request the Secretary of Health and Human Services to provide written recommendations … [regarding ] whether such drug is for a disease or condition which is rare in the United States…. [and] Prohibits the Secretary from approving any other applications or issuing any other licenses for an orphan drug until seven years after the initial application or license approval date….”
