Taking on FDA in court is a tough task since the agency wins far more cases than it loses. But Watson Laboratories Inc.’s recent victory in litigation over its generic Actos (pioglitazone) ANDA shows that companies have little to lose in challenging FDA decisions and can reap big rewards.

Watson objected to FDA’s award of 180-day marketing exclusivity to Ranbaxy Laboratories Ltd. for its generic version of the blockbuster diabetes drug. In a surprising ruling, the court ordered the agency to approve Watson’s ANDA, the first time a court has ever done so ([A#00121105006]).

The case is among a recent spate of suits drug makers have brought against the agency. Since March at least nine pharma-related complaints have been filed (see chart below). In most of these cases companies are seeking a court order to overturn FDA decisions on market exclusivity. In total, FDA now has 50 pending defensive cases.

Lawyers specializing in food and drug law say companies are more willing to sue FDA than they were in past years. This is driven on the generic side by a more competitive marketplace where winning a period of marketing exclusivity has become more crucial. Brand name companies meanwhile are watching their products fall off the patent cliff and seeking ways to delay generic competition.

Among the recent brand name company cases, Depomed Inc. filed suit to get orphan exclusivity for its Gralise (gabapentin); ViroPharma Inc. unsuccessfully sued to get three years of exclusivity for its Vancocin (vancomycin), arguing that its supplemental NDA included a significant new use; and AstraZeneca PLC sought to block generic versions of Seroquel (quetiapine) claiming it had exclusive right to clinical data in the labeling.

Frustration With FDA Is Spurring Some Suits

Kurt Karst, of Hyman, Phelps & McNamara, said the surge of suits this year is probably due to a conglomeration of factors. “Some of it is happenstance. Approvals come up and people sue,” he said. But he said some of the litigation may reflect frustration with the agency, as was the case in Apotex Inc.’s suit over FDA’s delay in approving its irbesartan ANDAs. The company claimed a paperwork snafu in the Office of Compliance stalled final approval of its generics.

Apotex quickly hammered out its differences with FDA. The agency approved the ANDAs, and the company dismissed the complaint on Oct. 17.

Meredith Manning, a partner at Hogan Lovells who represented Apotex in the case, attributed the uptick in litigation to “a sense that people are having more success” in being able to demonstrate arbitrary and capricious behavior by FDA.

“Perhaps what we’re seeing is a high frustration level [among companies] if they are not able to persuade FDA that its position is unfounded,” Manning said. In such situations “they are more willing to roll the dice.”

Former Apotex attorney Shashank Upadhye noted that some suits seek clarity about FDA’s rationale. Upadhye, now a partner at Seyfarth Shaw, cited Mylan Laboratories Ltd.’s complaint challenging the agency’s decision that Ranbaxy had not forfeited exclusivity for generic Diovan (valsartan). Mylan contends that Ranbaxy forfeited the award by failing to get tentative approval of its ANDA within 30 months of submitting its application.

“Mylan is trying to break through one sentence to see FDA’s reasoning,” Upadhye said, referring to the agency’s letter to Ranbaxy granting its ANDA tentative approval. In the letter, FDA noted that there had been a change to the USP monograph for valsartan, which was apparently the reason Ranbaxy did not lose exclusivity. Forfeiture does not apply if the failure to obtain approval was caused by a change in, or review of, approval requirements.

FDA has filed a motion to dismiss the suit, or alternatively, for summary judgment. Its memorandum in support of the motion was filed under seal, as were documents filed by Ranbaxy, which intervened as a defendant, and Mylan. A motions hearing is scheduled for Dec. 7.

Citizen Petitions Give FDA Ammunition

For its part, FDA believes companies are pursuing unwarranted claims against it.

“In my view, many of the generic drug lawsuits are unnecessary and have little chance of success,” Eric Blumberg, deputy chief counsel for litigation in FDA’s Office of Chief Counsel, said. “The potential rewards are sufficiently high that companies are overly optimistic about their chances of success, which results in the courts and FDA lawyers having to spend a lot of time evaluating and defending non-meritorious suits.”

The Office of Chief Counsel leads the charge against these suits. Its staff of approximately 100 attorneys -- 36 in the litigation unit and about double that in the counseling unit -- also helps craft regulations and oversees enforcement actions Also see "FDA’s Office of Chief Counsel Is Growing Its Ranks As It Amends Its Act" - Pink Sheet, 5 May, 2008..

In addition to defending the agency, the litigation unit also pursues enforcement cases against products from all FDA centers. Its active workload currently includes 70 injunctions, a dozen seizures, and several hundred civil complaints for violation of the Family Smoking Prevention and Tobacco Control Act. The unit also handles third party information requests, such as subpoenas and depositions. On the criminal side, 14 lawyers in the litigation unit work almost exclusively with the Office of Criminal Investigations. In addition, the OCC is assisting the Department of Justice with more than 100 qui tam cases.

The most recent data on the agency’s litigation success rate was published in an article in the March/April 2008 issue of the Food and Drug Law Institute’s Update magazine. Covington & Burling attorneys analyzed FDA’s 10-year track record in federal court and found that its win-loss record from 1998 to 2007 was roughly 55 to 25. Of the cases involving Hatch-Waxman litigation, FDA lost 11 of 44 court decisions.

Chad Landmon, a partner at Axinn, Veltrop & Harkrider who represented Watson in the Actos litigation, said that companies are more combative than they used to be. “Where the generic market is more competitive than it was five or 10 years ago, companies may feel that they need to be more aggressive,” he said.

However, he said that in the last three or four years FDA has rarely lost an exclusivity case. He attributes this in part to the citizen petition process. Generic parties used to file suit without filing citizen petitions, he said. But three or four year years ago FDA became more insistent that they file petitions. “Now through the citizen petition process FDA gets a couple hundred pages of legal briefs and comes up with a decision that anticipates everything that can come up in court,” he said.

Peter Barton Hutt, who created the citizen petition procedure during his tenure as FDA chief counsel in the 1970s, acknowledged that the goal was to curtail litigation. At the time, he said, FDA received numerous letters from people threatening to sue if the agency did not take some action. He would argue that they had to exhaust administrative remedies – i.e., the citizen petition process – before filing suit. If they did not do so, he would succeed in getting the court to dismiss the suit on the grounds they had not exhausted the administrative remedy.

“I thought [creating] this much-maligned citizen petition was one of the simplest and most important things I did,” Hutt said.

Hutt, senior counsel at Covington & Burling, also established the use of preambles in final rules and regulations, which have similarly deterred litigation. Hutt said that at the time his mentor correctly pointed out that in publishing a preamble he was filing his briefs in the Federal Register so no one would sue him. “Lots of people sued because they didn’t like a regulation,” Hutt said. “By putting out a reasonable explanation you would never lose.”

There has been no such defense against litigation over the Hatch-Waxman amendments. The exclusivity provisions have been particularly vexing for the agency. Elizabeth Dickinson, who took the helm as chief counsel in March, noted at a conference two years ago that the agency was looking to the courts for guidance on 180-day exclusivity questions. “There’s no way even 10 regulatory lawyers sitting around a table with many hours to work would come up with what you regularly bring us in terms of unbelievable fact patterns,” she said at the time. “Maybe we’ll get a sense of what the rules are from the courts as these [FDA decisions] are challenged” Also see "FDA Wrangles With Generic Exclusivity, Looks To Courts For Direction" - Pink Sheet, 18 October, 2010..

In one of the most significant cases, the U.S. District Court for the District of Columbia ruled in 2009 that FDA correctly interpreted the statute in denying Teva Pharmaceuticals USA Inc. 180-day marketing exclusivity for generic versions of the hypertension drugs Cozaar (losartan) and Hyzaar (losartan/hydrochlorothiazide). The agency had concluded that Teva lost rights to exclusivity because Merck had delisted patents on the drugs in FDA’s Orange Book. However, the U.S. Court of Appeals for the District of Columbia Circuit reversed the lower court opinion, ruling that brand name companies cannot trigger forfeiture of exclusivity by delisting their patents.

Abbott Is Expected To File Suit Over Its Biosimilars Citizen Petition

While FDA has prevailed in most of the recent exclusivity suits, it has suffered a string of losses in other areas this year. In September, the D.C. District Court vacated FDA’s decision that Prevor’s Diphoterine Skin Wash is a drug-device combination requiring data to support drug review. In August, an appeals court upheld the district court’s decision that FDA’s regulation requiring graphic warnings on cigarette packages was unconstitutional Also see "Labeling Regs Feel Ripple Effects From FDA’s Capsized Cigarette Warnings" - Pink Sheet, 5 March, 2012.. In March, the district court ruled in favor of death row inmates who sued FDA to block importation of sodium thiopental, finding that the foreign manufactured drug is misbranded and an unapproved new drug.

The agency will face more thorny issues in the future. Lawyers expect brand name companies to pursue more litigation against the agency. And once FDA begins to approve biosimilars, there will undoubtedly be litigation on the scale of Hatch-Waxman disputes. In the near term, lawyers say they expect Abbott Laboratories Inc. will file suit when the agency denies its citizen petition asking the agency not to approve a biosimilar that references an innovator biologics license application that was approved before March 23, 2010, the date legislation establishing a biosimilar approval pathway was enacted. The company argues that use of an innovator’s confidential data constitutes a “taking” of the BLA sponsor’s trade secrets under the Constitution’s Fifth Amendment Also see "FDA Biosimilar Guidances Stir Innovator Worries About BLA Exclusivity, Trade Secrets" - Pink Sheet, 30 April, 2012..

To date, only the Generic Pharmaceutical Association has submitted comments on Abbott’s petition. The association contends that, if granted, the petition would preclude the filing of any biosimilar application until sometime after March 2014 and the approval of any such application until sometime after 2022.

GPhA argues that the showings needed for approval of a biosimilar under the statute “are completely unrelated to the showings needed for approval of a BLA and require no reference to confidential data in the reference product’s BLA.” It says a BLA must demonstrate that the product is “safe, pure, and potent,” while a biosimilar application must show that the follow-on biologic is “biosimilar” to the reference product based on the applicant’s own data.

Taking On FDA: Major Bouts Of The Past Four Years

Below are suits that have been brought against the agency since February 2009. All of the complaints were filed in the U.S. District Court for the District of Columbia.

Suit

Date Filed/Issue

Status

Apotex Inc. v. HHS

12-01647

October 2012 – Apotex seeks an order directing the agency to issue final approvals of ANDAs for the antihypertensive drugs Avapro (irbesartan) and Avalide (irbesartan and hydrochlorothiazide)

FDA approved the ANDAs and Apotex voluntarily dismissed the suit Also see "Apotex’s Generic Approvals Delayed By FDA Paperwork Snafu, Lawsuit Says" - Pink Sheet, 4 October, 2012.

Mylan Laboratories Ltd. v. FDA

12-01637

October 2012 – Mylan requests the court to vacate FDA’s award of 180-day marketing exclusivity to Ranbaxy’s generic version of the antihypertensive Diovan (valsartan)

Motions hearing is scheduled for Dec. 7 Also see "Mylan vs. FDA (And Ranbaxy): Diovan Exclusivity Forfeiture Edition" - Pink Sheet, 4 October, 2012.

Depomed Inc. v. FDA

12-01592

September 2012 – Depomed seeks a court order directing FDA to grant Gralise (gabapentin) orphan exclusivity for post-herpetic neuralgia

Suit is pending ([A#14120926005])

Public Citizen Inc. v. FDA

12-01461

September 2012 – Public Citizen seeks to compel FDA to act on its citizen petition requesting that Aricept (donepezil) 23 mg tablets be withdrawn from the market and a warning be added to the labeling for 5 mg and 10 mg tablets of increased toxicity associated with higher dosages

FDA denied the citizen petition on Nov. 6

Watson Laboratories Inc. v. Sebelius

12-01344

August 2012 – Watson seeks an injunction to block FDA from approving any ANDA for generic Actos (pioglitazone) before approving its ANDA, or to require FDA to grant its ANDA final approval

Court ordered FDA to approve Watson’s generic Actos ANDA ([A#14121022007])

KV Pharmaceutical Co. v. FDA

12-01105

July 2012 – KV seeks court order requiring FDA to take enforcement action against pharmacies compounding hydroxyprogesterone caproate, the active ingredient in its preterm birth drug Makena

District court dismissed the suit, finding that FDA’s decision not to take enforcement action is within its discretion ([A#14120906004])

ViroPharma Inc. v. Hamburg

12-00584

April 2012 – ViroPharma challenges FDA’s approval of three ANDAs for generic Vancocin (vancomycin), claiming it qualifies for three years of exclusivity because its Vancocin supplemental NDA included a significant new use

District court denied company’s request for a preliminary injunction to force the agency to withdraw the ANDA approvals Also see "Antibiotic Indications: Definition Of “Significant” Remains In FDA’s Hands After Vancocin Ruling" - Pink Sheet, 24 April, 2012.

Teva Pharmaceuticals USA Inc. v. Sebelius

12-00512

Mylan Pharmaceuticals Inc. v. Sebelius

12-00524

April 2012 – Teva seeks preliminary injunction and temporary restraining order to prevent FDA from approving any other ANDA for generic Provigil (modafinil) until Teva’s exclusivity ends

FDA agreed to Teva’s argument and the complaint was withdrawn the day after it was filed. Mylan then sued FDA seeking to overturn its decision Also see "Provigil Generic Exclusivity Dispute Keeps Lawyers Up At Night" - Pink Sheet, 5 April, 2012.; a district court ruled in favor of FDA Also see "No Need To Fight: Teva Retains Provigil Generic Exclusivity Even Without “Adversarial” Relationship" - Pink Sheet, 24 April, 2012.

AstraZeneca Pharmaceuticals LP v. FDA

12-00388;12-00472

March 2012 – AstraZeneca files two suits against the agency, first trying to block it from approving generic versions of its atypical antipsychotic Seroquel (quetiapine) and then arguing it did not get to present a case that the approvals violate its exclusive right to clinical data in the labeling

District court denied request for preliminary injunction and granted FDA’s motion for summary judgment ([A#14120328006])

Par Pharmaceutical Inc. v. USA

11-01820

October 2011 – Par claims FDA regulations prohibit on-label speech about its appetite stimulant Megace ES (megestrol acetate) in settings where doctors prescribe it for both approved and off-label uses

Parties stayed the litigation while they work on a global settlement involving multiple government agencies Also see "Par Pursuing Settlement Of FDA Suit And DoJ Off-Label Investigation" - Pink Sheet, 25 July, 2012.

Hardy v. Shuren

11-01739

September 2011 – Six current and former FDA scientists allege FDA used spyware to obtain their private emails

The plaintiffs filed an amended complaint in January 2012 and at the order of a judge they filed a second amended complaint, Hardy v. Hamburg, in July Also see "FDA Email Spying: Crisis Experts Say Agency Needs To Tell Its Story Better" - Pink Sheet, 23 July, 2012.

Prevor v. FDA

11-01187

June 2011 – Prevor challenged FDA’s designation of Diphoterine Skin Wash, used to treat chemical burn injuries in the workplace, as a drug-device combination

Court granted Prevnor summary judgment in September 2012, vacating FDA’s decision that the skin wash required data to support drug review Also see "FDA Under Pressure On Its Approach To Assigning Combo Product Jurisdiction" - Pink Sheet, 1 October, 2012.

Ista Pharmaceuticals Inc. v. FDA

11-00907

May 2011 – Ista alleged FDA unlawfully approved Coastal Pharmaceuticals’ ANDA for a generic version of its eye-drop drug Xibrom (bromfenac)

Court granted FDA’s motion for summary judgment and issued an amended opinion and order in October 2012

Mylan Pharmaceuticals Inc. v. FDA

11-00566

March 2011 – Mylan seeks court order requiring FDA to announce whether Ranbaxy is eligible for 180-day marketing exclusivity for generic Lipitor (atorvastatin)

District court dismissed the suit saying Mylan lacked standing to sue until it obtained tentative approval of its atorvastatin ANDA Also see "Lipitor Generics: Questions About Mylan's ANDA Weigh Heavily In Court's Dismissal Of Lawsuit Against FDA" - Pink Sheet, 3 May, 2011.

Cephalon Inc. v. Sebelius

11-542

March 2011 – Cephalon seeks court order vacating FDA’s approval of Watson’s ANDA for generic Fentora (fentanyl buccal)

District court dismissed the suit for lack of ripeness ([A#14110316001])

Beaty v. FDA

11-00289

February 2011 – Death row inmates seek declaratory judgment that sodium thiopental is misbranded and unapproved and cannot lawfully be imported into the U.S.

District court permanently enjoined FDA from permitting the entry of, or releasing any future shipments of, foreign manufactured thiopental that appears to be misbranded; FDA has appealed the decision Also see "Imports Of Lethal Injection Drug A Law Enforcement Issue, FDA Says" - Pink Sheet, 14 February, 2011..

National Whistleblower Center v. HHS

10-2120

December 2010 – The National Whistleblower Center and six current and former FDA employees filed a Freedom of Information suit to obtain records regarding their complaints about misconduct by the agency and HHS in approval of medical devices and retaliation for their complaints

In a Nov. 9 ruling, the court found that the government properly withheld or redacted documents that were exempt from disclosure

Amphastar Pharmaceuticals Inc. v. FDA

10-01800

October 2010 – Amphastar requests declaratory judgment and injunction requiring FDA to release shipments of semi-purified heparin, and then seeks order requiring agency to approve its generic Lovenox (enoxaparin)

FDA approved Amphastar’s ANDA on Sept. 19, 2011, and the company dismissed its claims against the agency the following day Also see "Amphastar Seeks Court Order Requiring FDA To Approve Its Enoxaparin ANDA" - Pink Sheet, 3 January, 2011. and Also see "Momenta’s Generic Lovenox Suit Is Harbinger Of Biosimilar Battles Over Manufacturing" - Pink Sheet, 7 November, 2011.

ViroPharma Inc. v. Hamburg

10-01529

September 2010 – ViroPharma claimed FDA failed to conduct notice-and-comment rulemaking before changing its bioequivalence standards

Court dismissed the suit for lack of standing and ripeness and for failure to state a claim for which relief could be granted

Novartis Pharmaceuticals Corp. v. FDA

10-01611

September 2010 – Novartis sought order requiring FDA to withdraw approval of Watson’s ANDA for generic Famvir (famciclovir)

FDA switched the status of Watson’s ANDA approval to tentative and Novartis voluntarily dismissed the suit ([A#14100927002])

Sanofi-Aventis U.S. LLC v. FDA

10-01255

July 2010 – Sanofi challenges FDA’s approval of a generic version of its Lovenox (enoxaparin)

District court ruled in February 2012 that the agency acted properly in approving Sandoz’s ANDA Also see "Lovenox Generics: FDA’s Split Opinion On ANDA Approval Fully Supported By Court" - Pink Sheet, 7 February, 2012.

Apotex Inc. v. Sebelius

Roxane v. Sebelius

10-517

March 2010 – Apotex and Roxane file separate suits seeking preliminary injunction to block FDA from awarding Teva 180-day exclusivity for generic versions of the hypertension drugs Cozaar (losartan) and Hyzaar (losartan and hydrochlorothiazide)

District Court denied plaintiffs’ motions for a preliminary injunction finding FDA properly followed the logic of the D.C. Circuit’s decision in Teva Pharmaceuticals USA v. Sebelius Also see "Teva's Generic Exclusivity For Cozaar/Hyzaar Is Upheld By District Court; Apotex Appeals" - Pink Sheet, 5 April, 2010.

Matrixx Initiatives Inc. v. FDA

09-02406

Buc v. FDA

10-00293

December 2009 – Matrixx sought to obtain records related to the agency’s request for the recall of Zicam cold remedy nasal products

Court required FDA to produce the requested documents

Allergan Inc. v. USA

09-01879

October 2009 – Allergan claimed agency’s prohibitions on what it can tell physicians about unapproved uses of Botox violate the First Amendment

Allergan dropped the complaint in its settlement with the Department of Justice for off-label promotion of Botox Also see "Botox Reimbursement Training Is Driving Factor In Allergan Settlement With DOJ" - Pink Sheet, 1 September, 2010.

Sanofi-Aventis v. FDA

09-1495

August 2009 – Sanofi asked the court to rescind generic Eloxatin (oxaliplatin) approvals arguing that the 30-month stay of approval had been reinstated when the Federal Circuit vacated a district court decision that an Eloxatin patent was not infringed

Court ruled in FDA’s favor, holding that the appeals process has no bearing on approval of generics if the district court finds the patent is invalid or not infringed Also see "No Appeal: Eloxatin Decision Gives District Courts Primacy On 30-Month Stays" - Pink Sheet, 2 August, 2010.

Astellas Pharma US Inc. v. FDA

09-01511

August 2009 – Astellas sought a temporary restraining order and preliminary injunction requiring FDA to withdraw its approval of any generic version of Prograf (tacrolimus)

Court denied the company’s motion

Teva Pharmaceuticals USA Inc. v. Sebelius

09-5281

June 2009 – Teva sought a declaration that FDA’s determination that it was not due 180-day exclusivity for generic Cozaar and Hyzaar was unlawful and an injunction compelling FDA to award it exclusivity

District Court ruled that FDA’s interpretation of the Medicare Modernization Act was reasonable. But on March 2, 2010 the D.C. Circuit reversed, finding that brand companies could not trigger forfeiture of exclusivity by delisting their patents Also see "ANDA Exclusivity Protected From Patent Delisting Under Appeals Court Ruling" - Pink Sheet, 8 March, 2010.

Actavis Elizabeth LLC v. FDA

09-00362

February 2009 – Actavis sought ruling against FDA’s decision that Shire Pharmaceuticals’ Vyvanse (lisdexamfetamine) was entitled to five years of market exclusivity as a new chemical entity

The court ruled that FDA had correctly interpreted the statute and the D.C. Circuit upheld the decision Also see "Score Five For FDA: Shire's Vyvanse Entitled To NME Exclusivity, Court Finds" - Pink Sheet, 8 March, 2010.

FDA Hit With Slew Of Suits As Firms Fight For Market Advantage

More from United States

More from North America