Prepopik - USA

On Feb 13, 2018, Judge Rudolph Contreras of District of Columbia denied Ferring’s Motion to Enforce Judgment in PREPOPIK new chemical entity (NCE) exclusivity case.

Prepopik, a fixed-combination drug product used to cleanse the colon prior to colonoscopies, contains three active ingredients: sodium picosulfate, magnesium oxide, and anhydrous citric acid. While magnesium oxide and anhydrous citric acid had already been approved in previous New Drug Applications (“NDA”) when Ferring submitted its NDA for Prepopik, sodium picosulfate had not been. Therefore, when it submitted its NDA for Prepopik, Ferring also sought five years of exclusivity for the drug as a New Chemical Entity (“NCE”). The FDA approved Ferring’s NDA for Prepopik on Jul 16, 2012. However, the agency refused to grant Ferring five years of exclusivity for Prepopik because two of the active ingredients in the drug (magnesium oxide and anhydrous citric acid) existed in drugs previously approved by the FDA. Instead, it granted Ferring three years of exclusivity for new clinical investigation.

Ferring submitted a Citizen Petition requesting that the FDA change its exclusivity determination for Prepopik. A year later, the FDA issued a response to this Citizen Petition and Citizen Petitions filed by two other pharmaceutical companies & stated that it believed that its then-current interpretation of the relevant statute and regulations—that fixed-combination drugs that contain at least one previously approved active moiety cannot be granted exclusivity, even if the drug also contains at least one new active moiety—was “permissible.” After filing a Petition for Reconsideration and Petition for Stay, which the FDA denied, Ferring filed this action in federal court & sought “a declaratory judgment declaring that the FDA’s determination of the exclusivity period for Prepopik violates the [APA]” and “injunctive relief ordering the FDA to grant the full five years of exclusivity for Prepopik.” On first review, the Court denied Ferring all of the relief it requested [Ferring Pharm. Inc. v. Burwell (“Ferring I”), 169 F. Supp. 3d 199 (D.D.C. 2016)]. Following the Court’s grant of summary judgment to the FDA, Ferring moved for reconsideration on the grounds that it could identify several examples of a single-entity drug substance being denied five-year exclusivity due to the order in which the NDAs for drugs that include that substance were approved. The Court granted the motion for reconsideration, entered summary judgment for Ferring, and “remand[ed] th[e] action to FDA for further proceedings not inconsistent with [its] opinion.” Ferring Pharm., Inc. v. Burwell (“Ferring II”), No. 15-802, 2016 WL 4734333, at *11 (D.D.C. Sept. 9, 2016).

Throughout the NDA process, the NCE exclusivity Citizen Petition process, and this litigation, the FDA has consistently agreed with Ferring that the active moiety in sodium picosulfate is picosulfate. For example, when Ferring submitted its NDA for Prepopik, the FDA classified the NDA as a “Type 1 – New Molecular Entity” submission. Eight months after the Court remanded this matter back to the FDA for further proceedings consistent with its arbitrary and capriciousness finding, the FDA changed its mind regarding the identity of the active moiety in sodium picosulfate. It now believes, upon “further review,” that the active moiety in sodium picosulfate is not picosulfate, but rather bis-(p-hydroxyphenyl)-pyridyl-2-methane (BPHM), an active moiety that is also found in other previously approved drug products. As such, it concluded that Prepopik was not entitled to five-year NCE exclusivity. The agency’s change in position is based in its new chemical analysis of picosulfate.  Now the FDA explains that, following the Court’s remand, it has taken a closer look at the chemical properties of sodium picosulfate and “determined that sodium picosulfate is the disodium salt of a di-sulfate derivative of [BPHM],” because “[a]fter excluding the salt and ester portions of sodium picosulfate, as FDA’s regulations require, what remains is BPHM. After performing a “virtual hydrolysis to cleave all ester bonds,” and “[e]xamin[ing] the alcohol and acid components” to “determine which are ‘responsible for the physiological or pharmacological action of the drug substance,’” the FDA determined that the active moiety in sodium picosulfate is BPHM. It therefore concluded that “[d]espite [its] prior statements that sodium picosulfate was an NME and an NCE, it is now evident that those statements were incorrect because this drug substance contained a previously approved active moiety when it was approved in Prepopik.”

Ferring did not accept this conclusion, claiming that it resulted from a mid-adjudication change in the interpretation of the term “ester” to include “covalently bound sulfur-based appendages.” It argued that if the agency wanted to change its interpretation of the term “ester,” it should have followed the appropriate administrative procedures.  According to Ferring, the FDA’s “sudden reversal is not just an unreasonable break with past practice,” but also “an end-run around this Court’s” grant of summary judgment and remand order. Therefore, it has filed a motion to enforce the Court’s prior judgment, requesting that the Court “order FDA to award NCE exclusivity to Prepopik instead of ordering another remand.” Ferring argued that the FDA’s change in position regarding sodium picosulfate’s prior approval status violates the law of the case; that the agency is judicially estopped from changing its position in this manner; that the agency’s eleventh hour chemical analysis of sodium picosulfate impermissibly retroactively applies a new interpretation of the term “ester” and violates due process; and that the agency’s actions are arbitrary and capricious.

Ferring’s first argument was that the FDA’s change in position regarding the active moiety in sodium picosulfate violates the law of the case doctrine because the FDA’s actions on remand “undermine the clear thrust of this Court’s order instructing FDA to take further proceedings. The FDA counters that “[t]he doctrine of law of the case is inapplicable here because the factual issue of whether sodium picosulfate contains a new active moiety was never raised as a disputed issue to be decided during the litigation and FDA’s actions on remand were fully within the scope of the Court’s mandate.” Court sided with FDA & said that the FDA is correct that its determination regarding the active moiety in sodium picosulfate cannot be bound by the law of the case doctrine, though not, as it suggests, because the parties never disputed the issue. Court further held that at a basic level, Ferring’s argument that the law of the case applies here must fail because the Court never actually found that the active moiety in sodium picosulfate is picosulfate, either explicitly or by necessary implication.

Ferring’s second argument was that the FDA’s switch in position regarding the active moiety in sodium picosulfate is barred by judicial estoppel, which “prevents parties from abusing the legal system by taking a position in one legal proceeding that is inconsistent with a position taken in a later proceeding. The FDA responds that judicial estoppel does not apply because the agency did not intentionally change its position regarding the active moiety in sodium picosulfate in order to gain a tactical advantage in this suit, and because it never “succeeded in persuading [the Court] to accept [its] earlier position” regarding the active moiety in sodium picosulfate. Court held that the FDA is correct on both counts, and accordingly, the Court will not grant Ferring the relief it seeks on this ground either.

Court said that there is no doubt that Ferring is inconvenienced by the FDA’s new position that the active moiety in sodium picosulfate can be found in other, previously approved active ingredients. Indeed, had Ferring known that the FDA would argue that the active moiety in sodium picosulfate was BPHM rather than picosulfate, it may have decided not to pursue this litigation in the first place. At the very least, this revelation is a setback. However, this change in position certainly did not give the FDA an unfair advantage throughout the course of this litigation. Indeed, had the FDA staked out this position at the outset, it may have avoided litigating two dispositive motions regarding its prior interpretation of the NCE statutory and regulatory provisions, depending on how Ferring had chosen to respond. Because the FDA’s actions do not meet the three criteria set forth in Maine, and because it appears that the FDA’s late change in position may have been due to inadvertence or mistake, the Court does not find that the FDA is judicially estopped from determining that the active moiety in sodium picosulfate is BPHM, thereby denying Prepopik five years of exclusivity. Accordingly, the Court cannot grant Ferring the relief it seeks on this basis either.

Therefore for the reasons set forth above, the Court found that the FDA’s actions on remand do not violate the law of the case and that the FDA is not judicially estopped from asserting its change in position concerning sodium picosulfate’s prior approval status. The Court also found that Ferring’s arguments regarding retroactivity, due process, and arbitrary and capriciousness are not suitable for consideration within the context of a motion to enforce judgment. Thus Ferring’s Motion to Enforce Judgment is DENIED.