Lannett起诉FDA废除替莫唑胺胶囊ANDA批件

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Lannett Sues FDA Over Temozolomide Capsules ANDA Approval Rescission

By Kurt R. Karst –      

First, FDA gets hit with a June 27th preemptive lawsuit over approval of generic versions of CRESTOR (rosuvastatin calcium) Tablets; and then, on June 28th, a second lawsuit is filed by Lannett Company Inc. and Lannett Holdings, Inc. (collectively “Lannett”) challenging FDA’s recent rescission of Lannett’s ANDA 202750 for the oral chemotherapy drug Temozolomide Capsules, 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and 250 mg. It looks like it may not be much of an Independence Day Holiday for some of FDA’s attorneys.  

Lannett’s five-count Complaint was filed in the U.S. District Court for the District of Columbia and challenges FDA’s May 17, 2016 approval rescission of ANDA 202750 for Temozolomide Capsules, which the Agency had approved on March 23, 2016. According to FDA, the Agency approved the ANDA in error.  You see, ANDA 202750 apparently identifies Chinese company Chongqing Lummy Pharmaceutical Co. Ltd. (“Lummy”) as the manufacturer of the active pharmaceutical ingredient for the drug product.  FDA inspected Lummy in mid-March 2016.  On April 19, 2016, the Agency placed Lummy on Import Alert, pointing to concerns over the company's Current Good Manufacturing Practices (“CGMPs”) as the reason for the Import Alert; and on June 21, 2016, FDA issued a Warning Letter to Lummy summarizing significant CGMP deviations.

（2016年3月23日ANDA批准，2016年5月17日撤销ANDA批件，FDA解释为错误的批准该ANDA。主要原因是其ANDA申请中的中国供应商重庆莱美由于在2016年3月中旬的GMP检查发现不合规，并于2016年4月19日将该公司放上了进口禁令，并于2016年06月21日发布了重庆莱美相关问题的警告信。

（但是为什么FDA会存在这个错误呢？？是沟通问题？？？）

Lannett says in the Complaint that on April 1, 2016, FDA sent the company a “General Advice” letter “indicating that Lummy would not be releasing any new Temozolomide active pharmaceutical ingredient into the U.S. market until FDA deemed the Lummy facility acceptable.” FDA’s letter requested a call with Lannett to discuss two issues:

first, a commitment by Lannett not to distribute any Temozolomide drug product (or to recall drug product already distributed by Lannett; and

second, a “necessary withdrawal” of Lannett ANDA 202750.  After some further correspondence in which FDA gave Lannett three options –

(1) request FDA to withdraw approval of the ANDA;

(2) agree to immediate rescission of the ANDA approval; and

(3) provide FDA with information demonstrating that the compliance status at Lummy was acceptable as of March 23, 2016

– FDA issued an “ANDA Approval Rescission” letter on May 17, 2016.  According to Lannett:

（2016年04月01日FDA给lannett公司发了一份general advice信，并指明重庆莱美在其整改被FDA接受之前是不被允许API出口美国市场，general advice信中还要求和lannett公司讨论两个问题：第一,lannett公司承诺不再销售任何替莫唑胺药品（或召回,lannett已经分销的该产品），第二，有必要撤回该ANDA批件。经过后续的进一步沟通，FDA给出了3个选择：（1）要求FDA撤回该ANDA的批件，（2）答疑立即废除该ANDA批件，（3）提供FDA相关证据以证明2016年03月23日之前重庆莱美的GMP合规性。

据lannett透露，最终FDA在2016年5月17日发出了“ANDA批件废除”信。

(其中approval rescission和approval withdraw有什么区别？？？？）

The letter stated that while some FDA officials had information at the time of the ANDA approval indicating that Lummy’s compliance status was unacceptable, the “information was not adequately conveyed to the FDA officials making the final decisions about the ANDA approval.”（还是检查信息和批准决策之间信息沟通的问题） The letter also stated that the approval was a mistake. It stated that the agency had authority to rescind the ANDA, because the procedures of 21 U.S.C. § 355(e) do not apply, such that there is “no applicable statute displac[ing] FDA’s inherent authority to correct its mistake.” The agency concluded that “FDA is correcting its error and rescinding the approval letter issued for ANDA 202750 on March 23, 2016.”

（ANDA批件废除信陈述该ANDA的批准本身就是个错误，并且FDA声明其有权废除该ANDA批件，因为 21 U.S.C. § 355(e) 对此并不适用，以至于没有相关合适的法规条框能代替FDA固有的更正错误的权利）

Lannett alleges in the Complaint that FDA’s rescission of ANDA 202750 violates the Administrative Procedure Act (“APA”) and the Fifth Amendment’s due process right to a hearing in connection with deprivation of a property right. Lannett asks the court to, among other things, set aside and declare as unlawful FDA’s ANDA approval rescission, and to enjoin FDA from revoking the approval of ANDA 202750 without a hearing and the procedures established at FDC Act § 505(e).

（lannett公司则在投诉信中辩护，声称FDA废除该ANDA违反了行政程序法以及第五修正案关于剥夺财产权的举行听证的正当程序权利，lannett除了要求法院取消FDA对该ANDA的废除，并宣布FDA废除ANDA批件的不合法外，并要求禁止FDA在不举行听证和按照FDC Act § 505(e)规定的条件下废除该ANDA批件）

Various disputes concerning mistaken ANDA approvals and withdrawal (or suspension) of ANDA approvals have cropped up over the past few years. There’s Armenpharm, Ltd.’s recent opposition to FDA’s efforts to suspend the approval of the company’s ANDA 060851 for Chloramphenicol Capsules, 250 mg (see our previous post here).  Also, a couple of years ago, Mallinckrodt Inc. sued FDA after the Agency downgraded the company’s ANDA 202608 for generic CONCERTA (methylphenidate HCl) Extended-Release Tablets.  Among other things, Mallinckrodt argued that the downgrade was tantamount to withdrawal of ANDA approval (see our previous posts here and here).  There’s also the short-lived lawsuit Novartis Pharmaceuticals Corporation filed back in 2010 after FDA mistakenly approved ANDA 078278 for a generic version of FAMVIR (famciclovir) Tablets (see our previous post here).  And who could forget the litigation surrounding FDA’s decision to strip Ranbaxy Laboratories, Ltd. of tentative ANDA approvals for generic VALCYTE (valganciclovir) Tablets and NEXIUM (esomeprazole magnesium) Delayed-release Capsules (see our previous post here).

（各种对FDA的诉讼案例）

But perhaps the closest parallel to Lannett’s lawsuit is decades old.  Way back in 1989, FDA issued a letter to American Therapeutics, Inc. (“American Therapeutics”) rescinding approval of the company’s ANDA for Chlorzoxazone because of CGMP concerns, and shortly after the ANDA was approved.  American Therapeutics argued before FDA that the rescission is “an illegal action in violation of the FD&C Act, the Administrative Procedures Act, and [the company’s] fundamental due process rights guaranteed by the U.S. Constitution.”  Ultimately, American Therapeutics sued FDA (in D.C. District Court).  In February 1990, in American Therapeutics v. Sullivan, 755 F. Supp. 1 (D.D.C. 1990), the court ruled for FDA in a short decision:

There is no regulation or statutory provision that contemplates rescission of an approval issued by mistake. . . . FDA is entitled to some deference when its actions are examined. This was a good faith mistake promptly discovered and corrected, nothing more.  There is authority that suggests an agency must be given some leeway to remedy mistakes.  No precedent from this circuit has been cited that indicates a contrary approach.  It is not the function of a district court under these circumstances to intervene where an unresolved issue of statutory interpretation and administrative law within the exclusive jurisdiction of the Court of Appeals is presented.  [(Citations omitted)]

Where will the cards fall here given the American Therapeutics decision?  We’ll see soon enough.

beiwei5du

October 26, 2017

DC District Court Says FDA’s Rescission of a Mistaken ANDA Approval (and Placement Back Into the Review Queue) is Not Final Agency Action

By Kurt R. Karst –

Earlier this week, the U.S. District Court for the District of Columbia issued aMemorandum Opinion granting summary judgment to FDA in a lawsuit Lannett Company Inc. and Lannett Holdings, Inc. (collectively “Lannett”) filed in June 2016 challenging FDA’s rescission of Lannett’s ANDA 202750 for the oral chemotherapy drug Temozolomide Capsules, 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and 250 mg. (Copies of the briefs filed in the case are available here, here, here, and here.)

As we previously reported, on May 17, 2016 FDA issued a letter to Lannett rescinding the approval of ANDA 202750 for Temozolomide Capsules, which the Agency had approved on March 23, 2016. According to FDA, the Agency approved the ANDA in error.  ANDA 202750 identified Chinese company Chongqing Lummy Pharmaceutical Co. Ltd. (“Lummy”) as the manufacturer of the active pharmaceutical ingredient for the drug product.  FDA inspected Lummy in mid-March 2016, and on April 19, 2016, the Agency placed Lummy on Import Alert, pointing to concerns over the company’s Current Good Manufacturing Practices (“CGMPs”) as the reason for the Import Alert.  On June 21, 2016, FDA issued aWarning Letter to Lummy summarizing significant CGMP deviations.

Lannett alleged in a five-count Complaint that FDA’s rescission of ANDA 202750 violates the Administrative Procedure Act (“APA”) and the Fifth Amendment’s due process right to a hearing in connection with deprivation of a property right. Lannett asked the DC District Court to, among other things, set aside and declare as unlawful FDA’s ANDA approval rescission, and to enjoin FDA from revoking the approval of ANDA 202750 without a hearing and the procedures established at FDC Act § 505(e).

In a 17-page Opinion granting FDA’s Cross-Motion for Summary Judgment and denying Lannett’s Motion for Summary Judgment, Judge Reggie B. Walton concluded that FDA’s approval rescission of ANDA 202750 is not final agency action subject to APA judicial review, and that Lannett failed to exhaust available administrative remedies under 21 C.F.R. § 314.110(b) before filing its June 2016 Complaint.

FDA argued that Lannett’s lawsuit is essentially an attempt to bypass the administrative process, and that the doctrine of exhaustion of administrative remedies is a conclusive factor that should prevent the Court from consideration of Lannett’s claims at the present time. After all, argued FDA, the Agency “has not made a final, judicially reviewable decision on the manufacturing compliance status of the facilities named in Lannett’s ANDA,” because “[a]fter [the Agency] afforded Lannett due process and properly rescinded the ANDA approval, the application returned to pending status and was subject to regulatory requirements described in [FDA’s] Complete Response Letter.”

In response, Lannett argued that FDA’s ANDA approval rescission meets the test for a final agency action under the APA because it “was the consummation of the agency’s decision-making process to revoke the approval (not a tentative or interlocutory decision), and definitively adjudicated and revoked Lannett’s legal right to market Temozolomide capsules.” Lannett also asserted that the company “was not required to exhaust administrative remedies before filing this case” because FDA’s ANDA approval rescission “formally and definitively deprived [the company] of its legal entitlement to market Temozolomide capsules.”

After noting that “[a]An agency action is final if it ‘1) marks the consummation of the agency’s decision making process’ and 2) affects the ‘rights or obligations . . . [or the] legal consequences’ of the party seeking review,” and that whether “FDA’s rescission of a mistakenly approved ANDA and placement of that ANDA back into the review process queue is a final agency action” seems to be a case of first impression, Judge Walton proceeded with his analysis.

As to Lannett’s position that FDA’s action resulted in the “consummation of the agency’s decision-making process to revoke the approval” of ANDA 202750, Judge Walton said that that position “is too narrow for the Court to accept, primarily because Lannett’s position focuses solely on the rescission of the approval, which Lannett equates as a final agency action.”

Applying the principle that a court must look at the way in which an agency subsequently treats a challenged action when assessing whether a particular agency action qualifies as final for purposes of judicial review, Judge Walton concluded that “although the FDA did rescind Lannett’s ANDA approval, the FDA expressly advised Lannett that its ANDA was ‘now in pending status,’” among other things. As such, “FDA’s rescission action did not represent the conclusion of its decision-making process regarding the review process for Lannett’s ANDA or its ultimate decision to either approve or deny Lannett’s ANDA.”

And even if FDA’s ANDA approval rescission “could be perceived as the consummation of its decision-making process,” Judge Walton was not convinced that Lannett’s action satisfies the second prong of the finality doctrine above. Quoting from American Therapeutics v. Sullivan, 755 F. Supp. 1 (D.D.C. 1990) (here), a case that also involved FDA’s rescission of an ANDA approval because of CGMP concerns, Judge Walton wrote that Lannett “pictures itself, quite incorrectly, as having been deprived of a vested right.  [Rather, i]t had no right to put on the market a drug when facts were available indicating that the public health might be injured.”

Moving on to the doctrine of exhaustion of administrative remedies, Judge Walton concluded that “FDA’s rescission action cannot be considered final because Lannett has yet to exhaust all of its available administrative remedies.” Citing FDA’s regulation at 21 C.F.R. § 314.110(b) concerning Complete Response Letter actions, Judge Walton said that “Lannett was obligated to comply with the procedures provided in the FDA’s regulations by either resubmitting or supplementing its ANDA, withdrawing its ANDA, or requesting an opportunity for a hearing.”  But, instead of pursuing one of the specified actions, as the company should have done, “Lannett opted to file this action seeking judicial review.”

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