By Kurt R. Karst –      

It’s been nearly nine years since the enactment of the Medicare Modernization Act (“MMA”), which, among other things, changed the regime for 180-day generic drug marketing exclusivity from a “patent-by-patent” approach (under which shared exclusivity can exist for cross-Paragraph IV filers to different patents) to a “first applicant to any patent” approach.  Yet, the lawsuits against FDA involving pre-MMA 180-day exclusivity keep popping up.  Last year, there was the controversy over generic LIPITOR (atorvastatin calcium) Tablets.  Earlier this year there was the case involving generic PROVIGIL (modafinil) Tablets (see here).  The latest case, filed on August 15th in the U.S. District Court for the District of Columbia by Watson Laboratories, Inc. (“Watson”), involves generic versions of Takeda Global Research & Development Center, Inc.’s (“Takeda’s”) diabetes drug ACTOS (pioglitazone HCl) Tablets, 15 mg, 30 mg, and 45 mg.  Watson, through its Complaint and Motion for a Temporary Restraining Order and a Preliminary Injunction, seeks to enjoin FDA from granting final approval (or causing or allowing final approval to be granted) to any ANDA for generic ACTOS prior to granting final approval to Watson’s ANDA No. 076798, or, alternatively, to require FDA to approve ANDA No. 076798 if FDA grants final approval to any other ANDA for generic ACTOS.

Like almost all pre-MMA 180-day exclusivity cases, this case is complicated; but we’ll try to be brief.  FDA approved ACTOS on July 15, 1999 under NDA No. 021073 and granted a period of 5-year new chemical entity exclusivity.  At the time the first ANDA containing a Paragraph IV certification could be submitted to FDA on July 15, 2003, the Orange Book listed several patents for ACTOS.  One of those patents expired in 2006, and the others, which are referred to by Watson in its court filings as the Composition Patents and the Combination Therapy Patents, expire in 2016. 

Watson, and apparently Mylan (ANDA No. 076801) and Ranbaxy (ANDA No. 076800), all submitted ANDAs to FDA on July 15, 2003 containing Paragraph IV certifications to the Composition Patents and to the Combination Therapy Patents.  Prior to “receiving” (i.e., filing) the Watson ANDA on September 9, 2003, FDA instructed Watson (and presumably the others ANDA sponsors as well) to amend its proposed labeling and to change its Paragraph IV certifications to the Combination Therapy Patents to section viii statements (i.e., for labeling carve-out purposes).  Watson disagreed with FDA’s position, but made the certification change. 

After FDA received ANDA No. 076798, Watson provided notice of the Paragraph IV certifications as to the Composition Patents to Takeda and was sued for patent infringement, as were other ANDA sponsors.  Ultimately, the patent infringement litigation was settled and Takeda granted Watson, Mylan, and Ranbaxy a non-exclusive license to the Composition Patents and to the Combination Therapy Patents as of August 17, 2012.  Under FDA’s regulation at 21 C.F.R. § 314.94(a)(12)(v), “if the [ANDA] is for a drug or method of using a drug claimed by a patent and the applicant has a licensing agreement with the patent owner,” the application must contain a Paragraph IV certification as to that patent “and a statement that it has been granted a patent license.”  All three ANDA sponsors apparently amended their respective ANDAs to include Paragraph IV certifications Combination Therapy Patents.  But it is unclear when this happened exactly.  Timing is, of course, critical for 180-day exclusivity purposes.

According to Watson, “[b]ased on the simultaneous filing of the Watson ANDA with Mylan and Ranbaxy’s ANDAs, Watson has expected to share the period of 180-day exclusivity with Mylan and Ranbaxy (as well as with a fourth generic manufacturer, Teva Pharmaceuticals (‘Teva’), that has been granted a license by Takeda).”  In August 2012, however, Watsons says that “FDA informed Watson for the first time that approval of the Watson ANDA would be delayed.  FDA informed Watson it had reached a decision to award another filer or filers a period of 180-day exclusivity, to the exclusion of Watson’s ANDA, and to delay approval of Watson’s ANDA until the expiration of that exclusivity period.”  In other words, FDA presumably determined that one (or more) ANDA sponsor was first to convert its section viii statements to the Combination Therapy Patents to Paragraph IV certifications as a result of the settlement agreement, and that Watson subsequently converted.

Watson argues in its court papers that at the very least the company is entitled to shared exclusivity.  Watson’s primary arguments, however, are that FDA’s decision in this case that Watson’s ANDA cannot be approved as a result of another sponsor’s 180-day exclusivity “(i) contravenes the plain language of the statute and regulations, which only bars approval of later filed applications; and (ii) is contrary to FDA’s regulations and past practice, which deny exclusivity to any ANDA applicant for patents that are the subject of withdrawn or amended Paragraph IV certifications” (emphasis in original).  Accordingly, Watson says that the company is “entitled to an order requiring FDA not to approve any other pioglitazone ANDAs before it approves Watson’s ANDA.”

The case number is 12-cv-01344-ABJ. A hearing has been scheduled for August 15th.  We'll update this post with additional information.

UPDATE:

• August 15, 2012 Minute Entry: "Motion Hearing held on 8/15/2012 re [3] MOTION for Temporary Restraining [Order]; Motion heard and denied without prejudice."
• August 17, 2012 Minute Order: "As stated by the Court in its August 16, 2012 oral ruling, plaintiff's renewed motion for a temporary restraining order is denied. To demonstrate entitlement to a temporary restraining order or preliminary injunction, a litigant must show 1) a substantial likelihood of success on the merits; 2) that it would suffer irreparable injury if the injunction is not granted; 3) that an injunction would not substantially injure other interested parties; and 4) that the public interest would be furthered by the injunction. See Mova Pharm. Corp. v. Shalala, 140 F.3d 1060 (D.C. Cir. 1998) (setting forth standard for a preliminary injunction); Sterling Commercial Credit–Michigan LLC v. Phoenix Indus. I, LLC, 762 F. Supp. 2d 8, 78 (D.D.C. 2011) (stating that the same standard applies to temporary restraining orders and preliminary injunctions). For the reasons explained at the August 16, 2012 hearing, the Court finds that plaintiff did not show a substantial likelihood of success on the merits in its motion for a temporary restraining order concerning its abbreviated new drug application ("ANDA") for generic pioglitazone hydrochloride 15 mg, 30 mg, and 45 mg tablets ("Generic Pioglitazone"). Specifically, plaintiff was told by the Food and Drug Administration ("FDA") on August 15, 2012 that its application was deficient and that it was required to submit additional information. The Court denied plaintiff's initial motion for a temporary restraining order without prejudice in view of the FDA's request. Plaintiff then responded to the FDA's request and renewed its motion. During the August 16 hearing on plaintiff's renewed motion, the FDA informed plaintiff that it had not submitted sufficient information in response to the August 15 request. Accordingly, at that time, plaintiff's application was still deemed deficient by the FDA and plaintiff was unable to demonstrate a likelihood of success on the merits; indeed, plaintiff's counsel conceded that the Court could not grant injunctive relief if its application was deemed deficient. Even if plaintiff had provided sufficient information to the FDA prior to the August 17, 2012 release date of Generic Pioglitazone, however, the Court finds that plaintiff did not present the Court with any case law or other legal authority that would persuade the Court that it has the authority to compel the FDA to immediately process and approve Watson's ANDA under the facts of this case. Plaintiff's alternative requests for relief also fail. Plaintiff requested, inter alia, that the Court enjoin the FDA from approving any other company's ANDA for Generic Pioglitazone if the FDA were not to approve Watson's ANDA on August 17, 2012. This request fails because such relief would plainly cause substantial injury to the other providers of Generic Pioglitazone who would have been approved on August 17, 2012. Furthermore, the public interest would not be furthered by an injunction that prevents approved companies from selling a generic drug. Accordingly, for the reasons stated by the Court on August 16, 2012 and for the reasons explained above, plaintiff's motion for a temporary restraining order is DENIED. Signed by Judge Emmet G. Sullivan on August 17, 2012."

By Riëtte van Laack –

The Organic Food Products Act of 1990 (“OFPA”) established national standards for the marketing of certain agricultural products marketed as organically produced.  It directed USDA to issue regulations specifying the requirements for certification and labeling of organic agricultural products.  In promulgating the NOP regulations, the USDA decided that the labeling of cosmetics was outside the scope of the OFPA.  Although the USDA’s position appears to have changed over time, USDA has not amended its NOP regulations to apply to organic claims for cosmetics.

The California Organic Products Act of 2003 (“COPA”) prohibits any product handled, processed, sold, advertised, represented or offered for sale in California from being sold as organic unless it is labeled with terminology similar to terminology set for in the regulations by the National Organic Program (“NOP”). COPA specifically applies to cosmetic products sold or labeled as organic or made with organic.  Under COPA, cosmetics with organic claims must contain at least 70 percent organically produced ingredients.  Unlike OFPA, which may be enforced only by USDA, COPA is enforceable by any person who may bring an action for injunctive relief.

In 2011, R. Brown et al. filed a complaint against The Hain Celestial Group, Inc. (“Hain”), claiming that Hain sold organic cosmetics in violation of COPA because these cosmetics did not contain 70% or more organic ingredients.  Hain filed a motion to dismiss arguing that COPA’s requirements for cosmetics are expressly preempted by the federal OFPA.

Judge Beeler of the U.S. District Court for the Northern District of California disagreed, however, in a decision from earlier this month.  Although the title of the OFPA may suggest otherwise, the Court concluded that OFPA covers cosmetics that use agricultural products.  However, the court held that OFPA only expressly preempts a narrow set of state certification requirements and does not bar state law labeling provisions that do not conflict with OFPA’s and NOP’s provisions.  In the alternative, even if (contrary to the Court’s interpretation) OFPA does not extend to agricultural cosmetics, USDA has approved COPA.  In either case, COPA’s provisions regarding organic claims for cosmetics are not preempted.  Therefore, the Court denied the Hain’s motion to dismiss.

By Jennifer D. Newberger –

On August 10, 2012, FDA issued a draft guidance, “Refuse to Accept Policy for 510(k)s.”  This draft guidance largely mirrors the recently issued draft guidance for premarket approval applications, “Acceptance and Filing Review for Premarket Approval Applications (PMAs),” on which we previously commented here. 

The draft guidance includes checklists for traditional, abbreviated, and special 510(k)s, based largely on the regulatory requirements for 510(k)s outlined in 21 C.F.R. § 807.87.  Included in the checklist are elements that will not necessarily be applicable to all devices, e.g., biocompatibility testing.  If a submitter believes that a particular element is not relevant to the submission, it should provide a justification for not including the information.

Within 15 days of receipt of the submission, FDA must inform the submitter if the submission is administratively complete, or, if not, identify the missing elements.  The submitter may then respond by providing the missing information, and FDA will then have another 15 days to perform the acceptance review.  The submitter should provide the information under the originally assigned 510(k) number.  FDA will not require a complete new submission, nor will the submitter be required to pay a new user fee upon providing the missing information.

The guidance states that if FDA fails to complete the acceptance review within 15 days, the submission should be considered accepted, but “FDA may ask for any information during the substantive review that may have been unintentionally overlooked during the acceptance review.”  The review clock for MDUFA goal purposes will not begin until FDA determines that the submission is administratively complete.  This review does not assess whether the contents of the application are substantively sufficient to make a substantial equivalence determination. 

The guidance contains certain principles that it suggests reviewer and submitters should heed in determining whether a 510(k) submission is complete:  1) acceptance should not be based on a substantive review of the submission; 2) reviewers should consider any justifications provided by the submitter as to why certain elements are not included, and; 3) submitters should review any applicable guidance or standards to ensure the submission contains all necessary information for that device type.

The guidance provides preliminary questions to be addressed by the reviewer prior to determining whether the submission contains all elements in the checklist.  These questions include:  (1) Is the product a device? (2) Is the submission within the correct center (e.g., CDRH or CBER)?  (3) Is a 510(k) is the appropriate regulatory submission?  (4) Is there a pending PMA for the same device with the same indications?  (5) If clinical data are submitted, is the submitter subject to the Application Integrity Policy (AIP)?  Though most of these questions could be easily answered during a preliminary review, determining whether the 510(k) path is appropriate could require a more substantive review, and may not always easily be determined.  For some products, it also may not be as clear as to whether the product is a device (see, e.g., here).  If a submitter is unsure of the appropriate regulatory path prior to providing a submission to FDA, it should consider submitting a 513(g) to determine FDA’s likely regulatory approach. 

It’s that time of year again when we at FDA Law Blog turn to our loyal readers and ask for your help.  The American Bar Association (“ABA”) announced that it is now accepting nominations for the 2012 Blawg 100 (the top 100 legal blogs – or “blawgs” – in the blogosphere).  With your help we made the top 100 list in 2009 and 2010, and we would really like to do so again in 2012!  We’d like another merit badge to add to the growing “Awards and Honors” collection posted on our blog. 

We ask that FDA Law Blog readers use the ABA’s Blawg 100 Amici Form – available here – and nominate the FDA Law Blog!  Although it’s called a “friend-of-the-blawg brief,” filling out the form will take only a couple of minutes.  In fact, you only have 500 characters to say why you’re a fan of the blog (something pithy).  Remember, when you complete the nomination form, our URL is www.fdalawblog.net.  Friend-of-the-blawg briefs are due no later than Friday, September 7th.

ABA editors make the final decisions about what’s included in the Blawg 100.  We hope they’ll be impressed with what our readers have to say about us.  Thank you!

By Kurt R. Karst –      

That’s the picture conjured up when we plugged some dates into the new model for calculating forfeiture of 180-day generic drug marketing exclusivity for certain ANDAs – what we are calling “window ANDAs” – covered by Section 1133 of the recently enacted FDA Safety and Innovation Act (“FDASIA”).

FDASIA § 1133 concerns FDC Act § 505(j)(5)(D)(i)(IV), which is one of the six 180-day generic drug exclusivity forfeiture provisions added to the FDC Act by Title XI of the 2003 Medicare Modernization Act.  Under FDC Act § 505(j)(5)(D)(i)(IV), 180-day exclusivity eligibility is forfeited if:

The first applicant fails to obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed.

The 2007 FDA Amendments Act clarified FDC Act § 505(j)(5)(D)(i)(IV), such that if “approval of the [ANDA] was delayed because of a [citizen] petition, the 30-month period under such subsection is deemed to be extended by a period of time equal to the period beginning on the date on which the Secretary received the petition and ending on the date of final Agency action on the petition (inclusive of such beginning and ending dates) . . . .” FDC Act § 505(q)(1)(G). 

FDASIA § 1133 covers two cohorts of ANDAs – one under subsection (a) and another under subsection (b).  For both sets of ANDAs covered by FDASIA, the intent of the law is two-fold.  First, FDASIA accounts for FDA’s growing median ANDA approval time – about 32-33 months today – which has led to many companies forfeiting 180-day exclusivity eligibility.  Second, FDASIA § 1133 addresses FDA’s strict interpretation of FDC Act § 505(j)(5)(D)(i)(IV), such that when an ANDA sponsor who amends a long-pending ANDA to include a Paragraph IV certification to an Orange Book-listed patent and qualifies as a “first applicant,” that sponsor may simultaneously forfeit 180-day exclusivity eligibility for failure to obtain timely tentative approval.  This has happened because FDA counts 30 months from the ANDA submission date rather than from the first Paragraph IV certification date (see our previous post here).

FDASIA § 1133(a) covers ANDAs submitted to FDA between January 9, 2010 (actually, January 11, 2010, because January 9th is a Saturday) and July 9, 2012 initially containing a Paragraph IV certification to a patent listed in the Orange Book for the Reference Listed Drug (“RLD”), or that is amended between January 9, 2010 and July 9, 2012 to first contain a Paragraph IV certification to a patent listed in the Orange Book for the RLD.  It provides that the time to obtain timely tentative approval (or final approval if tentative approval is not warranted) is 40 months during the period of July 9, 2012 and September 30, 2015, and not 30 months.  During the period beginning on October 1, 2015 and ending on September 30, 2016, the period is 36 months and not 30 months.

FDASIA § 1133(b) covers ANDAs first amended after July 9, 2012 to contain a Paragraph IV certification.  Specifically, this subsection provides that for an ANDA submitted to FDA prior to July 9, 2012 that is first amended on July 10, 2012 and up to September 30, 2017 to contain a Paragraph IV certification to a patent listed in the Orange Book for the RLD, the date of the amendment starts to 30-month tentative approval forfeiture period instead of the original ANDA submission date. 

While all seems well with the FDASIA § 1133(b) window ANDAs, there appears to be a problem with the FDASIA § 1133(a) window ANDAs.  In particular, the 36-month extension date is inapplicable (absent an applicable 505(q) citizen petition, or some change in review that occurs during the last 6 months of the 36-month period making the forfeiture provision irrelevant).  By the time this provision takes effect on October 1, 2015, the youngest ANDA to which it could apply – i.e., an ANDA submitted to FDA on July 9, 2012 – will be nearly 39 months old.  If such an ANDA is tentatively approved on September 30, 2015 when the tentative approval period is still 40 months, there would not be a forfeiture.  If, however, that same ANDA is tentatively approved one day later, on October 1, 2015, there would be an automatic forfeiture.

In addition, we note that the youngest window ANDA to which FDASIA § 1133(a) can fully apply (i.e., an ANDA that could potentially enjoy the full 40-month period absent an applicable 505(q) citizen petition) is an ANDA submitted on May 30, 2012 and tentatively approved on September 30, 2015.  Such an ANDA would be tentatively approved within the 40-month period (depending on what it means to be tentatively approved “within” the specified timeframe – see our previous post here.)  An ANDA submitted after May 30, 2012 would not enjoy the full 40-month period. 

By Larry K. Houck –
 
The Drug Enforcement Administration (“DEA”) recently amended its regulations to allow practitioners to issue electronic prescriptions for controlled substances (“EPCS”) in lieu of hardcopy paper prescriptions.  See 75 Fed. Reg. 16,236 (March 31, 2010).  DEA requires that any electronic prescription application or pharmacy application used for EPCS must be reviewed, tested and determined by a third party to meet all of the required technical specifications.  21 C.F.R. § 1311.300(a).  As an alternative to the third party audit requirements of 21 C.F.R. §§ 1311(b)-(d), an electronic prescription or pharmacy application may be verified and certified as meeting DEA requirements by a certifying organization whose certification process has been approved by DEA.  21 C.F.R. § 1311.300(e).  DEA stated that it would notify registrants of any approved third party certifications on its website.  75 Fed. Reg. 16,243.

DEA announced on August 1, 2012 that it has approved the certification processes developed by two certifying organizations (77 Fed. Reg. 45,688 (Aug. 1, 2012)) and has posted relevant information about those approvals, and about an earlier approval, on the DEA Diversion Control website.   

By Kurt R. Karst –      

There’s a first time for everything!  And on August 8th, 2012, FDA decided, for the first time since the enactment of the Orphan Drug Act, to rescind a period of 7-year orphan drug exclusivity.  The decision came in the form of a response granting in part and denying in part a citizen petition (Docket No. FDA-2011-P-0213) CSL Behring (“CSL”) submitted to FDA in March 2011 requesting that the Agency: (1) revoke the orphan drug designation and the period of orphan drug exclusivity FDA subsequently granted to Octapharma USA, Inc. (“Octapharma”) for the December 4, 2009 approval of WILATE (von Willebrand Factor/Coagulation Factor VIII Complex (Human)) under BLA No. 125251 “for the treatment of spontaneous or trauma-induced bleeding episodes in patients with severe von Willebrand disease (VWD) as well as patients with mild or moderate VWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated;” and (2) “refrain from making any orphan drug designations and approval decisions based on hypothetical claims of superiority.”  FDA decided not to revoke orphan drug designation for WILATE, and also denied CSL’s request regarding “hypothetical claims of superiority.”

WILATE is the “same drug” as HUMATE-P (Antihemophilic Factor/von Willebrand Factor Complex (Human)) for orphan drug purposes.  That is, FDA considers them to be “chemically the same drug” and for the same orphan indication.  FDA approved HUMATE-P on April 1, 1999 for the same orphan disease as WILATE.  Because WILATE is the “same drug” as HUMATE-P, the issue of “clinical superiority” comes into play – for obtaining orphan drug designation and for obtaining orphan drug exclusivity.

FDA’s orphan drug regulations at 21 C.F.R. § 316.20(a) state that “a sponsor of a drug that is otherwise the same drug as an already approved orphan drug may seek and obtain orphan-drug designation for the subsequent drug for the same rare disease or condition if it can present a plausible hypothesis that its drug may be clinically superior to the first drug.”  FDA’s orphan drug regulations define a “clinically superior” drug as “a drug . . . shown to provide a significant therapeutic advantage over and above that provided by an approved orphan drug (that is otherwise the same drug)” in one of three ways: (1) greater effectiveness as assessed by effect on a clinically meaningful endpoint in adequate and well controlled trials; (2) greater safety in a substantial portion of the target population; or (3) demonstration that the drug makes a major contribution to patient care.

As FDA explains in the petition response (as well in the Agency’s 2011 proposed rule – see our previous post here):

Though the sponsor of a subsequent orphan drug must set forth a plausible hypothesis of clinical superiority over the previously approved drug at the designation stage, such a sponsor faces a higher standard at the time of approval.  At approval, the sponsor of a drug which was designated on the basis of a plausible hypothesis of clinical superiority must demonstrate that its drug is clinically superior to the previously approved drug.  Should the sponsor fail to do so, then the subsequent drug will be considered to be the same drug as the previously approved drug, and will not be able to gain marketing approval if the previously approved drug’s orphan-drug exclusive approval period is still running.  Once this exclusivity has expired, the subsequent drug may be approved . . . , but it will not be eligible for orphan-drug exclusivity because the same drug has already been approved for the same orphan indication.

In the case of WILATE, FDA designated the drug as an orphan drug in April 2007 after determining that there was a plausible hypothesis of clinical superiority.  Specifically, FDA determined that WILATE “may be safer than [HUMATE-P] in a substantial portion of the target population due to its two dedicated viral inactivation steps compared to a single dedicated viral inactivation step for [HUMATE-P].”  After approving WILATE, FDA allowed Octapharma to make its case for a demonstration of clinical superiority, and on June 24, 2010, FDA determined that WILATE “appeared to be clinically superior to [HUMATE-P] because of greater viral safety,” and, in fact, “had been shown to be clinically superior to [HUMATE-P] within the meaning of the FDA’s orphan drug regulations . . . .”  As such, FDA granted a period of 7-year orphan drug exclusivity retroactive to December 4, 2009 when FDA approved WILATE.

CSL subsequently contacted FDA and questioned the evidentiary support for FDA’s exclusivity decision.  FDA requested that CSL raise its concerns in a citizen petition, which CSL submitted in March 2011.  CSL’s main premise is that the evidence Octapharma presented to FDA to support clinical superiority of WILATE over HUMATE-P does not meet the applicable regulatory standards. 

After reanalyzing available evidence, FDA concluded that WILATE had not, in fact, been demonstrated to be clinically superior to HUMATE-P due to greater safety.  According to FDA, “the record does not contain sufficient evidence to support a finding that Wilate is clinically superior to Humate due to its ‘[g]reater safety in a substantial portion of the target population.’”  Accordingly, FDA withdrew its clinical superiority determination, and, as a result, rescinded the orphan drug exclusivity for WILATE. 

FDA decided not to rescind orphan drug designation for WILATE, however.  FDA’s orphan drug regulations provide three independent bases under which orphan drug designation can be revoked – if FDA finds that: 

(1)  The request for designation contained an untrue statement of material fact; or

(2)  The request for designation omitted material information required by [21 C.F.R. Part 316]; or

(3)  FDA subsequently finds that the drug in fact had not been eligible for orphan drug designation at the time of submission of the request therefor. [(21 C.F.R. § 316.29(a))] 

FDA rarely rescinds orphan drug designation.  We are aware of only three instances:

(1) Papaverine – On February 6, 1992, OOPD designated Pharmedic Co.’s papaverine topical gel for the “treatment of sexual dysfunction in spinal cord injured patients.”  FDA revoked the designation on September 16, 1993 after additional information showed that the potential target population of the drug could be significantly larger than originally stated.

(2) Methylnaltrexone – On June 17, 1996, FDA designated the University of Chicago’s methylnaltrexone for the “treatment of chronic opioid-induced constipation unresponsive to conventional therapy.”  FDA revoked the designation on January 9, 1998 after new information indicated that the drug could be used in a significantly larger patient population.

(3) Pancreatic Enzymes – On January 23, 2002, FDA designated Altus Biologics Inc.’s TheraCLEC-Total, a microbially-derived pancreatic enzyme product containing amylase, lipase, and protease, as an orphan drug for the “treatment of exocrine pancreatic insufficiency.”  FDA revoked the designation on June 28, 2007 based on information showing that the drug could be used in a significantly larger patient population – specifically HIV/AIDS patients who suffer from fat malabsorbtion (see our previous post here).

In each of these cases, orphan drug designation was revoked because FDA determined (see 21 C.F.R. § 316.29(a)(3)) that the drug “had not been eligible for orphan drug designation at the time of submission of the request.”  In 2011, FDA denied a petition seeking the revocation of orphan drug designation for MAKENA (then known as GESTIVA), which is another orphan drug the orphan drug exclusivity of which has been in the news as of late (see here).

With respect to the orphan drug designation for WILATE, FDA concluded that although WILATE’s “hypothesis of clinical superiority has not been demonstrated to be true,” that does not mean that the plausible hypothesis of clinical superiority “was implausible ‘at the time the [designation] request was submitted.’  The salient fact is that, at the time Octapharma advanced it, the designation request presented a plausible hypothesis.”  As such, according to FDA, none of the grounds in FDA’s regulation to rescind designation apply.

FDA also denied CSL’s second request concerning “hypothetical claims of superiority,” because “‘hypothetically plausible’ is the very standard that the Agency applies to designation requests under its orphan drug regulations.”

Octapharma submitted comments to the petition docket advancing several arguments.  Among other things, Octapharma claimed that the company has “a Constituionally-protected interest” in the orphan drug exclusivity FDA granted for WILATE, and that FDA may not rescind exclusivity without providing the company an opportunity to defend its exclusivity interest at a formal hearing.  FDA reiterated the Agency’s position that “a manufacturer has no property right in its orphan-drug exclusivity that would entitle it to the sort of process to which Octapharma claims it is entitled.” 

By Carmelina G. Allis –

On August 2, 2012, the FDA published a final rule amending its regulations in 21 C.F.R. Part 807 to reflect the 2007 statutory amendments to the device registration and listing provisions of the Federal Food, Drug, and Cosmetic Act ("FDC Act").  This final rule also facilitates the FDA’s collection of additional registration information in order to comply with the 2002 Bioterrorism Act.

The most significant change is that all contract manufacturers and contract sterilizers must now register and list.  This change eliminates the long standing exemption for contract manufacturers and sterilizers who performed these activities for another party who both initiated the specifications and commercially distributed the device.  77 Fed. Reg. 45,927, 45,941 (Aug. 2, 2012) (amending 21 C.F.R §§ 807.20(a)(3) and (c)(1) to remove this exemption).

The usual registration user fee will apply.  The FY 2012 establishment registration fee is $2,020.  In FY 2013, the fee will be $2,575 (see our previous post here).

There also are new requirements for foreign establishments to identify all known importers and to register/list even when their devices enter a foreign trade zone.  According to FDA, these requirements will comply with the Bioterrorism Act, and help increase the Nation’s ability to prepare for an respond to acts of bioterrorism and other public health emergencies.

The regulation also has been revised to require that all registration and listing information be submitted electronically to FDA (absent a waiver).  This formally implements the 2007 statutory amendments, although FDA in fact has been requiring electronic regulation for several years now.

The effective date of the final rule is October 1, 2012.

Hyman, Phelps & McNamara, P.C. is pleased to announce that Anne Walsh will moderate a panel on “Trends and Priorities in Enforcement” at this year’s Food and Drug Law Institute’s (“FDLI”) Advertising and Promotion Conference.  The conference will be held in Washington, DC on October 1-2, 2012.  Panelists will include speakers from the HHS OIG, DOJ, and the states, and will complement Ms. Walsh’s former experience at FDA.  They will discuss what can be learned from recent settlements involving medical product advertising and promotion. 

FDLI’s annual Advertising & Promotion conference brings together regulated industry and the regulators responsible for overseeing the advertising and promotion of prescription drugs, medical devices, biologics, and animal drugs. Top-level officials from FDA’s four medical product-related Centers (CBER, CDER, CDRH, and CVM), and speakers from GlaxoSmithKline, Abbott, Pfizer, Merck and Medtronic (a full list of speakers is online) will provide helpful insight and be available to answer your questions during panel discussions and networking opportunities.

This conference is attended by experienced professionals in the fields of regulatory, legal, public relations, marketing and management who work in the pharmaceutical, medical device, diagnostic, biologics and veterinary medicine industries. The conference is also beneficial for consultants in the areas of advertising, public relations, law and marketing communications.

FDA Law Blog readers can receive a 15% discount off the conference registration price.  To receive the discount, use the following promotional code: AP2012.  For more information and to register, visit the program website.

By Kurt R. Karst –      

We were eager to delve into the Federal Circuit’s recent 2-1 decision in Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc. (Docket Nos. 2012-1062, -1103, -1104) concernng the scope of the Hatch-Waxman “safe harbor” provision at 35 U.S.C. § 271(e)(1), particularly in light of the Court’s prior decision in Classen Immunotherapies v. Biogen IDEC, 659 F.3d 1057 (Fed. Cir. 2011), which is on appeal to the U.S. Supreme Court (Docket No. 11-1078).  Although the 2012 London Olympics captured most of our attention over the weekend, we did find some time to look over the decision.  And we weren’t disappointed – at least insofar as the decision, and Chief Judge Randall Rader’s dissent, provided some legal entertainment.

The case involves a generic version of LOVENOX (enoxaparin), which FDA approved after addressing active ingredient sameness criteria (i.e., “standards for identity”) in a citizen petition response (see our previous post here), U.S. Patent No. 7,575,866 (“the ‘866 patent”) assigned to Momenta that generally relates “to methods for analyzing heterogeneous populations of sulfated polysaccharides” such as enoxaparin, and 35 U.S.C. § 271(e)(1), which states: 

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention (other than a new animal drug or veterinary biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Act of March 4, 1913) which is primarily manufactured using recombinant DNA, recombinant RNA, hybridoma technology, or other processes involving site specific genetic manipulation techniques) solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

Momenta sued Amphastar for patent infringement alleging that Amphastar infringed the ‘886 patent by manufacturing for commercial sale enoxaparin using the patented method.  Ultimately, the U.S. District Court for the District of Massachusetts granted Momenta a preliminary injunction and denied two emergency motions filed by Amphastar for relief from the preliminary injunction.  (Copies of those decisions are available here, here, and here.)  Among other things, the District Court ruled that Amphastar’s activity fell outside of the “safe harbor” provision at 35 U.S.C. § 271(e)(1), because:

although the safe harbor provision permits otherwise infringing activity that is conducted to obtain regulatory approval of a product, it does not permit a generic manufacturer to continue in that otherwise infringing activity after obtaining such approval. . . .  Here, the alleged infringing activity involves use of plaintiffs’ patented quality control testing methods on each commercial batch of enoxaparin that will be sold after FDA approval.  Thus, it is not exempted under § 271(e)(1).

In coming to its decision, the District Court relied on the U.S. Supreme Court’s decision in Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005), and on the Hatch-Waxman legislative history of 35 U.S.C. § 271(e)(1) quoted by the Federal Circuit in Classen; namely that:

[T]he only activity which will be permitted by the bill is a limited amount of testing so that generic manufacturers can establish the bioequivalency of a generic substitute . . . .  [T]he generic manufacturer is not permitted to market the patented drug during the life of the patent; all that the generic can do is test the drug for purposes of submitting data to the FDA for approval.  [H.R. Rep. No. 98–857, at 8 (1984)]

In Integra, the Supreme Court stated that the text of 35 U.S.C. § 271(e)(1) “makes clear that it provides a wide berth for the use of patented drugs in activities related to the federal regulatory process,” and that there is “no room in the statute for excluding certain information from the exemption on the basis of the phase of research in which it is developed or the particular submission in which it could be included.”  In Classen, which concerned whether a vaccine license holder was required to report to FDA certain adverse event information, the Federal Circuit held that 35 U.S.C. § 271(e)(1) “does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained.”

Amphastar appealed each of the District Court’s preliminary injunction decisions to the Federal Circuit and argued that the District Court improperly took a restrictive view of the “safe harbor” provision.  Momenta argued that the District Court’s decisions were correct and that, among other things, the Federal Circuit in its Classen decision previously ruled that 35 U.S.C. § 271(e)(1) does not apply to routine reports to FDA post-approval, such as the batch testing Amphastar carried out as a condition to ANDA approval of its generic LOVENOX.  (Copies of the Amphastar and Momenta Federal Circuit briefs are available here, here, and here.)

The Federal Circuit first sought to ascertain the scope of 35 U.S.C. § 271(e)(1) and focused on the the passage in the “safe harbor” provision stating “solely for uses reasonably related to the development and submission of information under a federal law.”  According to the Court:

Congress could not have been clearer in its choice of words: as long as the use of the patented invention is solely for uses “reasonably related” to developing and submitting information pursuant to “a Federal law” regulating the manufacture, use, or sale of drugs, it is not “an act of infringement.” . . .  Limiting the scope of 35 U.S.C. § 271(e)(1) to just the submission of information pursuant to the [FDC Act] generally, or to the ANDA provision of the [FDC Act] in specific, would read words into the statute in violation of the express language chosen by Congress.

Moreover, while the statute does include a limitation – that the use must be “for uses reasonably related to the development and submission” – the term “reasonably related,” says the Court, citing and quoting Integra, “does not mean that the use of the patented invention must necessarily result in submission of information to the FDA.”   Rather, “[a]s long as the accused infringer has a reasonable basis for believing that use of the patented invention might yield information that would be appropriate to include in a submission to the FDA, that use is ‘reasonably related’ to the ‘development and submission of information’ . . . .”  (internal quotations omitted).

(Although this question is perhaps best reserved for another day, given the Federal Circuit’s broad reading of the “safe harbor” provision, would the Court perhaps include in its interpretation of 35 U.S.C. § 271(e)(1) information related to a biosimilar application under PHS Act § 351(k)?)  

Noting that the information Amphastar produced was not actually submitted to FDA, but rather is retained by the company, the Federal Circuit next addressed whether such information can nevertheless be “submitted” for purposes of 35 U.S.C. § 271(e)(1).  And the court said “yes,” stating:

We think that the requirement to maintain records for FDA inspection satisfies the requirement that the uses be reasonably related to the development and submission of information to the FDA. . . .  The fact that the FDA does not in most cases actually inspect the records does not change the fact that they are for the “development and submission of information under a Federal law.”

Then came the big issue: whether Amphastar’s submissions are within the 35 U.S.C. § 271(e)(1) “safe harbor.”  Here again, the Federal Circuit said “yes” (because they are required “submissions”), and in doing so addressed the Classen decision:

This case . . . fits well within Classen because the information submitted is necessary both to the continued approval of the ANDA and to the ability to market the generic drug.  Here, the submissions are not “routine submissions” to the FDA, but instead are submissions that are required to maintain FDA approval. . . .

Under a proper construction of 35 U.S.C. § 271(e)(1), the fact that Amphastar’s testing is carried out to “satisfy the FDA’s requirements” means it falls within the scope of the safe harbor, even though the activity is carried out after approval.  Unlike Classen, where the allegedly infringing activity “may” have eventually led to an FDA submission, there is no dispute in this case that Amphastar’s allegedly infringing activities are carried out to “satisfy the FDA’s requirements.”  The district court’s interpretation of § 271(e)(1) was erroneous.  Under the correct construction, Momenta cannot establish a likelihood of success on infringement and the preliminary injunction must be vacated.

The Federal Circuit also disagreed with Momenta’s argument that Amphastar’s testing is not protected under 35 U.S.C. § 271(e)(1) because there are non-infringing alternatives available that are endorsed by FDA. 

Chief Judge Rader, who hesitantly noted that he was present through the Hatch-Waxman legislative process (see here), lodged a blistering 29-page dissent that begins and ends with the conclusion that Amphastar is a trespasser.  In between, Chief Judge Rader provides a history of 35 U.S.C. § 271(e)(1), saying that the provision “won approval because it was limited in time, quantity, and type,” and that the majority opinion runs counter to legislative intent and significantly expands the scope of the provision.  According to Chief Judge Rader:

This new interpretation would allow almost all activity by pharmaceutical companies to constitute “submission” and therefore justify a free license to trespass.  The FDA can inspect records of any drug manufacturer and seller.  See 21 U.S.C. § 374.  Thus, the drug manufacturer need only make a record, which could potentially be inspected by the FDA, and then any activity could satisfy this new meaning of “submission.”

Moreover, says Chief Judge Rader, the majority decision cannot be reconciled with the Federal Circuit’s Classen decision, and the “decision should instead request the entire court to resolve the issue en banc.”  Although we’ve made such predictions before and they did not pan out (to our surprise), this Federal Circuit decision seems destined to further appeal.

By Kurt R. Karst –      

There’s a lot of parlance (legal and scientific) bandied about in the food and drug world, and perhaps nowhere more so than in the world of Hatch-Waxman.  Things can get confusing.  Take, for example, the term “Reference Listed Drug,” or “RLD.” 

FDA’s regulation at 21 C.F.R. § 314.3(b) defines the term “reference listed drug” to mean “the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its abbreviated application.”  (A “listed drug” is defined in the same regulation to mean, in part, “a new drug product that has an effective approval under section 505(c) of the act for safety and effectiveness or under section 505(j) of the act. . . .”). 

Fast forward through the Code of Federal Regulations to FDA’s ANDA content and format regulations, which require, among other things, that an ANDA sponsor identify a basis for submission.  Specifically, 21 C.F.R. § 314.94(a)(3) says that an ANDA “must refer to a listed drug.  Ordinarily, that listed drug will be the drug product selected by the agency as the reference standard for conducting bioequivalence testing” (emphasis added).  That “reference standard” is identified in the paper version of the Orange Book with a “+”.  (The electronic version of the Orange Book does not use “+”.  Instead, it has a column titled “RLD” where each drug product listing is set to either “Yes” or “No.”) 

Now on to the Preface to the Orange Book, which states the following in a section titled “Reference Listed Drug (RLD)”:

A reference listed drug (21 CFR 314.94(a)(3)) means the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its ANDA.

FDA has identified in the Prescription Drug Product and OTC Drug Product Lists those reference listed drugs to which the in vivo bioequivalence (reference standard) and, in some instances, the in vitro bioequivalence of the applicant's product is compared.  By designating a single reference listed drug as the standard to which all generic versions must be shown to be bioequivalent, FDA hopes to avoid possible significant variations among generic drugs and their brand name counterpart.  Such variations could result if generic drugs were compared to different reference listed drugs. 

Unfortunately, none of these references clearly delineate what we’ll call the “big RLD” and the “little rld.”  Instead, they tend to mosh them together. 

So . . . . When someone uses the term “reference listed drug,” is that person referring, generally, to a drug approved under an NDA (i.e., the “big RLD”), or to the particular reference standard identified in FDA’s Orange Book with a “+” (i.e., the “little rld”)?  Not understanding the difference between the “big RLD” and the “little rld” can lead to faulty decisions and costly mistakes – at least insofar as decisions to submit ANDAs are concerned.  

Here’s an example to illustrate this point . . . .  FDA approves an NDA for a drug with multiple strengths but delays making a decision on which particular strength is the reference standard (i.e., which strength should get the “+” in the Orange Book).  Generic Company No. 1 takes a “big RLD” approach.  It believes that all that is needed as a basis for ANDA submission is a drug approved under an NDA.  It does not wait for FDA to identify a reference standard and instead conducts bioequivalence testing on all of the approved strengths and submits its ANDA with a Paragraph IV certification to an Orange Book-listed patent.  Generic Company No. 2 takes a “little RLD” approach.  It thinks that FDA must first add the “+” in the Orange Book for a particular strength, becuase without it there is not a basis for ANDA submission.  As such, it waits for FDA to identify a specific reference standard, then conducts bioequivalence testing and submits an ANDA with a Paragraph IV certification to an Orange Book-listed patent. 

Which company, Company No. 1 or Company No. 2, was smarter?  Answer: Company No. 1, which in this scenario would have submitted the first ANDA to FDA containing a Paragraph IV certification making that company eligible for a period of 180-day marketing exclusivity.  Why?  Because Company No. 1 correctly understood that all that is needed as a basis for ANDA submission is an approved NDA drug to reference (along with, of course, bioequivalence data and information).  FDA does not need to identify a particular reference standard before accepting an application. 

REMINDER:  You can follow us on Twitter @fdalawblog

By Riëtte van Laack –

The U.S. Government Accountability Office ("GAO") released a report on FDA’s  food recall process prepared in response to a congressional directive in the Food Safety Modernization Act ("FSMA"), which provided FDA with mandatory recall authority for foods.  In evaluating FDA’s implementation, the GAO considered how other government entities with recall authority, such as the Consumer Product Safety Commission, handle recalls and advise the public.

Since FSMA was enacted in 2011 and therefore FDA’s mandatory recall authority is relatively new, there is no information about an actual mandatory recall of food.  Moreover, although FDA has had mandatory recall authority for other product categories such as medical devices, the Agency has rarely used that authority.  Nevertheless, GAO developed some recommendations for FDA to more effectively implement and strengthen its new mandatory recall authority.  Specifically, GAO recommends that FDA:

• publish its currently internal document describing the steps it takes to order a food recall;
• document its process for ordering food recalls in regulations or guidance, including the process of weighing whether a recall is warranted and whether the standard of proof for a mandatory recall is met;
• define categories of ordered recalls in FDA’s central recall database;
• determine and implement ways to improve the sharing of information among databases that contain recall information.

GAO also examined the challenges FDA faces in advising the public about food recalls or outbreaks of foodborne illness.  GAO acknowledged that FDA faces a number of communication challenges when advising the public about food recalls or outbreaks of foodborne illness, ranging from balancing technical accuracy with timeliness of communications, to coordinating messages with other agencies and meeting the needs of diverse public audiences.   For example, a delay in communication can result in more illnesses and deaths, but a premature communication can trigger major financial losses for the food industry and deter the consumption of certain healthful foods.  GAO further recognized that FDA has taken steps to begin meeting these challenges, but concluded that FDA has yet to fully address recommendations from the GAO and others to fashion a comprehensive food recall communication policy and related implementation plans.  

GAO recommends that FDA implement recommendations from others to address FDA communication challenges when advising the public about food recalls and outbreaks. Specifically, GAO recommends that FDA:

• develop a policy for communications during emerging events;
• implement a coordinated plan for crisis communication; and
• consult with USDA on USDA’s experiences in advising consumers about recalls and determine whether those experiences may be helpful for FDA.

Although a significant part of the report is devoted to a discussion of possible options to compensate the food industry for erroneously ordered recalls, the report does not include a specific recommendation for a mechanism.

By Ricardo Carvajal –

According to an informal policy, FDA considers the use of the term “natural” in food labeling to mean that nothing artificial or synthetic (including colors regardless of source) is included in, or has been added to, the product that would not normally be expected to be there.  Cases dealing with this policy typically focus only on whether the food contains an artificial or synthetic substance, and do not address the italicized element.  So we couldn’t help but notice when a California district court delved into the issue in a recent opinion that keeps alive a class action against Dreyer’s Grand Ice Cream (“DGIC”).

In relevant part, the court refused to dismiss state law claims essentially alleging that Haagen-Dazs ice cream was falsely advertised as “All Natural Ice Cream” despite the fact that it contained cocoa alkalized with potassium carbonate, a substance alleged to be artificial or synthetic.  Among other things, DGIC argued that, “because potassium carbonate is commonly used as an alkanizing agent. . . nothing artificial or synthetic has been used in its ice cream.”  The court found this argument problematic:

[E]ven if potassium carbonate is commonly used, that does not necessarily imply normally expected; a reasonable consumer may not have the same knowledge as, e.g., a commercial manufacturer.

Thus, at least in this court’s eyes, the presence of an artificial or synthetic substance is compatible with a “natural” claim only if one can demonstrate that consumers normally expect the substance to be present.  Awareness of the presence of the substance among manufacturers is irrelevant. 

By Jamie K. Wolszon –

FDA published in the July 31, 2012 Federal Register a notice announcing the Fiscal Year (“FY”) 2013 rates pursuant to the third iteration of the Medical Device User Fee Act (“MDUFA III”), which was recently enacted as part of the FDA Safety and Innovation Act (“FDASIA”), Pub. L. No. 112-144, 126 Stat. 993 (2012) (see our summary).  The notice includes the fee for establishment registrations, which FDASIA broadened to include many more establishments than in the past.

The device user fee schedule establishes the Premarket Approval (“PMA”) Application fee as the baseline fee, with other fees tied to that fee.  For instance, MDUFA III sets 510(k) fee amounts at 2% of PMA fees.  The fee for a PMA in FY 2013 will be $248,000.  This baseline also applies to BLAs (for devices regulated by CBER), Product Development Protocols (“PDPs”) (which are essentially never submitted), a premarket report (seeking permission from FDA to market a reprocessed version of a class III single-use device) and a BLA efficacy supplement.

The notice also sets out the fees for PMA supplements, notices, and reporting.  The fee for a panel-track supplement will be $186,000.  The fee for a 180-day supplement will be $37,200.  The fee for a real-time supplement will be $17,360.  The fee for a 30-day notice will be $3,968.  The annual fee for periodic reporting on a class III device will be $8,680.

The fee for a 510(k) premarket notification submission will be $4,960, while the fee for a 513(g) request for classification information will be $3,348.

The fee for annual establishment registration is $2,575.  FDASIA significantly expanded the scope of establishments subject to the annual establishment registration.  Prior to enactment of MDUFMA III, only three types of establishments were subject to registration fees: (1) manufacturers; (2) single-use device reprocessors; and (3) specifications developers. MDUFA III broadened the fee to apply to any establishment that is “engaged in the manufacture, preparation, propagation, compounding, or processing of a device.”

The fees are outlined in Table 1 of the Federal Register notice, and go into effect on October 1, 2012.  They are generally modest increases to the fees for FY 2012.

MDUFA III also includes a provision permitting FDA to waive medical device fees, or reduce applicable fees, if it is in the interest of public health.  The Federal Register notice does not discuss how FDA intends to apply that new discretion. On the drug side, FDA has published a guidance that discusses, among other waivers and reductions, waivers and reductions to prescription human drug user fees necessary to protect the public health. 

By Kurt R. Karst –      

Ever since the U.S. Court of Appeals for the First Circuit issued its opinion in May 2012 in Bartlett v. Mutual Pharmaceutical Co., ___ F.3d ___, 2012 WL 1522004 (1st Cir. May 2, 2012) denying Mutual Pharmaceutical Company’s (“Mutual’s”) appeal of a decision from the U.S. District Court for the District of New Hampshire in which the district court denied Mutual’s Motion for Judgment as a Matter of Law – see Bartlett v. Mutual Pharm. Co., 760 F. Supp. 2d 220 (D.N.H. 2011) – concerning design defect and generic drug preemption, there’s been a lot of speculation that Mutual would petition the U.S. Supreme Court to review the case.  That day has come with Mutual’s July 31st Petition for Writ of Certiorari.

The Bartlett case has a long history in federal court beginning with a September 2009 pre-Mensing decision (see our previous post here), and then, after a couple of additional district court decisions, ending (until now) with the First Circuit’s post-Mensing decision.  Our Mensing reference, of course, refers to the U.S. Supreme Court’s June 23, 2011, 5-4 landmark decision in PLIVA Inc. v. Mensing, 131 S.Ct. 2567 (2011), in which the Court ruled that FDA’s regulations preventing generic drug manufacturers from changing their labeling except to mirror the label of the brand-name manufacturer (whose drug product is approved under an NDA) preempt state-law failure-to-warn claims against generic drug manufacturers, because generic drug manufacturers are unable to comply with both federal and state duties to warn.  This is in contrast to the Court’s March 4, 2009 decision in Wyeth v. Levine, 555 U.S. 555 (2009), holding that a state-law tort action against a brand-name drug manufacturer for failure-to-warn is not preempted.  Since the Supreme Court issued its Mensing decision, scores of court decisions have dismissed litigation against generic drug manufacturers on Mensing grounds, including some Circuit Court decisions.  The Drug and Device Law Blog maintains a Generic Drug Preemption Scorecard of the decisions.

The drug at issue in Bartlett is Sulindac Tablets, a non-steroidal anti-inflammatory drug. Mutual markets the drug under an ANDA FDA approved in 1991 (ANDA No. 072051).  (Mutual’s product is an AB-rated version of Merck’s CLINORIL (sulindac) Tablets, which FDA approved in September 1978 under NDA No. 017911.)  The Bartletts (Respondents) claim that Mrs. Bartlett suffered serious injuries after taking Mutual’s Sulindac Tablets and raised myriad state-law tort claims.  Those claims were ultimately winnowed down to a state-law design defect claim that proceeded to trial.  (Specfically, the claim that “sulindac’s risks outweighed its benefits making it unreasonably dangerous to consumers, despite the [FDA] having never withdrawn its statutory ‘safe and effective’ designation that the original manufacturer had secured and on which Mutual was entitled to piggyback,” which goes to the very core of the generic drug system established under the Hatch-Waxman Amendments.)  A jury eventually awarded Respondent over $21 million in damages, and the district court denied various post-trial motions filed by Mutual, including Mutual’s renewed preemption defense based on the Supreme Court’s Mensing decision. 

Mutual appealed to the First Circuit, which affirmed the district court in a decision that our friends over at the Drug and Device Law Blog characterized as an “essentially absurd result.”  In reaching its decision, the First Circuit first turned not to Mensing, but to Wyeth, saying that although Wyeth, which did not involve a design defect claim, “was technically limited to failure-to-warn claims, its logic applies to design defect claims as well.”  Moreover, according to the Court, Mensing merely “carved out an exception to Wyeth, finding that the FDCA preempts failure-to-warn claims against generic drug manufacturers . . . [because] the generic maker cannot alter the labeling.”  That is, the Supreme Court “adopted a general no-preemption rule in Wyeth. . . .”  Based on this thinking, the First Circuit concluded that to avoid state tort law liability a company could simply stop making its generic drug product. 

Setting the case up for a request for Supreme Court review, the First Circuit commented that “it is up to the Supreme Court to decide whether [Mensing’s] exception is to be enlarged to include design defect claims. . . .  Given the widespread use of generic drugs and the developing split in the lower courts . . . , this issue needs a decisive answer from the only court that can supply it.”  And maybe that will happen with Mutual’s Petition for Writ of Certiorari, which presents the following question for the Supreme Court: 

Whether the First Circuit erred when it created a circuit split and held—in clear conflict with this Court’s decisions in PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011); Riegel v. Medtronic, Inc., 552 U.S. 312 (2008); and Cipollone v. Liggett Group, Inc., 505 U.S. 504 (1992)—that federal law does not preempt state law design-defect claims targeting generic pharmaceutical products because the conceded conflict between such claims and the federal laws governing generic pharmaceutical design allegedly can be avoided if the makers of generic pharmaceuticals simply stop making their products.