Amphastar Seeks Court Order Requiring FDA To Approve Its Enoxaparin ANDA

Amphastar’s initial lawsuit against FDA achieved its stated goal: the agency released two shipments of raw heparin material the company is to use in producing generic Lovenox (enoxaparin).

But Amphastar contends that FDA is continuing to put up obstacles to prevent approval of its enoxaparin ANDA and has filed an amended complaint asking the court to order FDA to halt this behavior and to approve its generic version of Sanofi-Aventis’ anticoagulant.

With those requests, Amphastar has moved beyond the relief sought by Sandoz in its seminal suit against FDA, where it tried to force the agency to make a decision on its Omnitrope (somatropin). That suit had simply asked for an action letter on the application for the follow-on growth hormone (Also see "Sandoz Sues FDA For Inaction On Omnitrope NDA" - Pink Sheet, 14 Sep, 2005.).

Amphastar's amended suit goes a step further in asking for approval, and it remains to be seen how comfortable the courts will be trying to compel FDA behavior in this area given that they have historically deferred to the agency's scientific judgment. Omnitrope, of course, ended up winning approval after a favorable court decision, and if Amphastar finds the relief it wants, the emerging biosimilar pathway could move as much through the halls of justice as the halls of FDA.

It seems the firm's original suit has already produced some positive actions from FDA even without a judicial decision, and Amphastar now wants to expand and codify that.

Amphastar filed suit on Oct. 25 requesting a declaratory judgment and injunction requiring FDA to release shipments of semi-purified heparin produced by Amphastar Nanjing Pharmaceuticals (Also see "Amphastar Lawsuit Over Heparin Shipments Suggests Lovenox ANDA Approval May Be Far Off" - Pink Sheet, 1 Nov, 2010.). FDA detained the material after it was shipped to Amphastar’s International Medication Systems subsidiary in South El Monte, Calif.

In the amended complaint, filed Dec. 22 in U.S. District Court for the District of Columbia, Amphastar states that three days after it began the litigation FDA wrote a letter to the company dropping one of its stated reasons for the detentions. Amphastar says it sent information requested by FDA – which it says it had already provided seven times – and the agency released the shipments on Nov. 8.

But, the amended complaint says, “FDA left the door open to further obstruction, stating that it has not yet made ‘a final decision’ on whether Entries 1 and 2 [the two shipments] are exempt from FDA labeling requirements.” FDA had previously said the materials were misbranded as they lacked adequate directions for use. Amphastar argued that raw materials are exempt from this labeling requirement.

Court Asked To Find FDA Favoritism

The revised complaint asks the court to issue a declaratory judgment that FDA acted unlawfully in detaining the shipments. And it goes much further, asking the court to rule the agency acted unlawfully in favoring Amphastar’s competitors and to direct FDA to approve its enoxaparin.

The litigation is part of a long battle Amphastar has waged alleging FDA favoritism in its handling of Sandoz and Momenta’s ANDA for enoxaparin. Amphastar filed its ANDA for the anticoagulant in 2003 and Sandoz submitted its application in 2005. FDA approved the Sandoz/Momenta product in July.

Amphastar immediately sent the agency a letter requesting it to rescind approval, saying the heparin in the Sandoz product was being supplied by Chinese manufacturers under investigation for heparin contamination that occurred in late 2007 and early 2008 (Also see "Lovenox Lawsuit May Be Omen For Biosimilar Battles" - Pink Sheet, 2 Aug, 2010.).

Amphastar’s Heparin Supplier Is Still Subject To FDA Scrutiny

The amended complaint says FDA is continuing to “impose new pretextual roadblocks to approval of Amphastar’s ANDA,” including its refusal to lift an April 2009 warning letter issued to Amphastar’s heparin supplier, Qingdao Jiulong Biopharmaceuticals Co. Ltd.

The warning letter claims QJBC manufactured heparin contaminated with oversulfated chondroitin sulfate (OSCS), which the complaint says was at the heart of the heparin crisis and found in virtually the entire heparin supply chain in 2008.

The complaint says QJBC only manufactures starting material for Amphastar’s enoxaparin ANDA and thus the standards for manufacturers of drugs or active pharmaceutical ingredients do not apply to it. Nevertheless, Amphastar said it has encouraged QJBC to cooperate with FDA.

The supplier conducted an independent audit of its facility in China in May 2009, which the complaint says was favorable to the company, and was re-inspected by FDA in November 2009. The complaint says FDA made 19 observations based on the re-inspection; the complaint did not identify what they were. Amphastar said it responded to each observation as well as a follow-up letter FDA sent in July 2010.

The complaint says FDA sent another letter on Nov. 30, 2010 raising points previously addressed by Amphastar and QJBC and requesting a third inspection of QJBC.

“FDA’s actions appear designed to send Amphastar and QJBC back to ‘square one’ over and over again, which would enable the FDA to further delay approval of Amphastar’s ANDA,” the complaint states.

The complaint also reiterates Amphastar’s previous allegation that Center for Drug Evaluation and Research Director Janet Woodcock had conflicts of interest with Momenta and its co-founder Ram Sasisekharan, who played a leading role in FDA’s investigation into the causes of the heparin crisis.

It further contends that the agency has engaged in “arbitrary, capricious, and vindictive behavior” against Amphastar. For example, it says that between February 2008 and December 2009, the agency inspected Amphastar facilities approximately 15 times within the span of 94 working days “without finding anything more than extremely minor deficiencies with Amphastar.”

The complaint also says that FDA forced Amphastar to discontinue production of its six critical care drugs at the end of 2009, while allowing Amphastar’s competitor producing the same drugs to remain on the market. The complaint says that in July FDA requested Amphastar to reintroduce them because of a severe shortage of the drugs.

Amphastar asks the court to rule that FDA is acting unlawfully in its treatment of QJBC and to issue a permanent injunction directing FDA to lift the warning letter issued to QJBC. It also requests a permanent injunction directing FDA to recuse Woodcock from all Amphastar-related matters pending before the agency.

By Brenda Sandburg