By Riëtte van Laack –

Legislation that would require labeling of genetically engineered or bioengineered foods (generally referred to as “GMOs”) has been proposed in various states.  If enacted, these state laws may expose companies to a patchwork of different GMO labeling requirements. 

On April, 10, 2014, Representatives Mike Pompeo (R-KS) and G. K. Butterfield (D-NC) introduced legislation that would nullify the efforts in multiple states to require labeling of GMOs.  H.R. 4432, the “Safe and Accurate Food Labeling Act of 2014” (“SAFLA”), would amend the FDC Act to include a provision preempting any state requirement regarding the sale, distribution, or marketing of a bioengineered organism intended for food use or application, and regarding food products from, containing, or consisting of a bioengineered organism.  We note that this clause does not appear to allow state laws that are identical to the federal law. 

SAFLA would require premarket review the safety of GMOs.  A company would be required to submit a premarket biotechnology notification to FDA at least 210 days before introduction into commerce of a GMO.  This notification would provide FDA with information about the notifier’s determination that food produced from or containing the GMO is as safe as the food from the non-GMO variety.  FDA would get 30 days to inform the notifier that the notification is complete or identify missing information.  Once FDA has informed the notifier that the notification is complete, the Agency would get 180 days for substantive review of the notification.  If FDA decides that the GMO variety is safe but materially different from the non-GMO variety and that disclosure of this material difference is necessary to protect the health and safety of consumers or to prevent the labeling from being false and misleading, FDA may require specific labeling for the GMO variety.

Although the bill essentially would prohibit mandatory GMO labeling unless FDA determines that such labeling is necessary, it specifically would allow “non-GMO” claims.  Such claims would be permitted only if the ingredients are subject to certain supply chain process controls and meet certain limits for the presence of inadvertent GMOs.  FDA is to promulgate regulations that specify a maximum level of inadvertent GMOs that would be permissible in non-GMO foods.

The bill also addresses natural claims.  It would require that FDA issue regulations defining “natural” within 12 months after enactment of the law.  FDA has previously declined to address the term for courts (see our prior post here), but was recently petitioned to promulgate a regulation.

By Ricardo Carvajal & Diane B. McColl –

When GAO issued its 2010 report criticizing FDA’s oversight of the GRAS exception, we were motivated to respond first in short form in a blog post, and then in long form through a Washington Legal Foundation Legal Backgrounder.  In the years since, attacks on the GRAS exception have grown increasingly shrill and detached from reality, so we thought it would be a worthy exercise to begin cataloguing the principal errors and mischaracterizations underpinning those attacks.  Even if one presumes that FDA’s oversight of the GRAS exception needs to be improved, knowing which improvements would be beneficial would require an accurate diagnosis of where problems might lie.  Many of the diagnoses offered thus far are based on unwarranted assumptions, erroneous analyses, and factual misrepresentations.  The catalogue of such flaws has grown so vast that we don’t aim to complete our task in a single blog posting – thus the designation of this posting as Part 1 of a series that we’ll continue in the coming weeks.

We begin with the report that the Natural Resources Defense Council ("NRDC") released earlier this week, Generally Recognized as Secret: Chemicals Added to Food in the United States.  That report contends that the GRAS exception is “the loophole that swallowed the law.”  According to the revisionist history of the Food Additive Amendments of 1958 ("FAA") offered in the report:

The 1958 law exempted from the formal, extended FDA approval process common food ingredients like vinegar and vegetable oil that are “generally recognized as safe” (GRAS). It may have appeared reasonable at the time, but that exemption has been stretched into a loophole that has swallowed the law. . . .

Congress concluded that the FDA would make all safety decisions, except in the most obvious situations in which a chemical’s use in food was “generally recognized as safe.”  This is known as the GRAS exemption.  Examples include such common food ingredients as oil and vinegar.

The suggestion that the GRAS exception was intended only for common household food ingredients like oil and vinegar is repeated on NRDC’s website, both in text and video formats (see here).  That suggestion is, at the least, misleading.

In passing the FAA, Congress was well aware that numerous substances other than common food ingredients would be eligible for GRAS status.  That is evident in FDA’s first GRAS list, which was published shortly after the law’s passage.  In publishing that list, FDA stated: 

It is impractical to list all substances that are generally recognized as safe for their intended use. However, by way of illustration, the Commissioner regards such common food ingredients as salt, pepper, sugar, vinegar, baking powder, and monosodium glutamate as safe for their intended use.  In addition, the following lists include some substances that, when used for the purposes indicated, in accordance with good food manufacturing practice, are regarded by the Commissioner as generally recognized as safe for such uses. [(Emphasis added.)] 

The lists compiled by FDA included dozens of substances in the categories of buffers and neutralizing agents, sequestrants, antimycotics, antioxidants, nonnutritive sweeteners, and emulsifying agents, among others.  The existence of FDA’s first GRAS list is known to the authors of the NRDC report because they cited to it in one of their earlier PEW publications (see Navigating the U.S. Food Additive Regulatory Program, at 347).  Evidently, acknowledging the variety and nature of the substances on the first GRAS list has grown inconvenient, as it undermines one of the NRDC report’s central claims – namely that both FDA and industry have perverted the original purpose of the law.

Even a cursory reading of the FAA’s legislative history makes clear that the law was intended to achieve two principal purposes, only one of which was to ensure the safety of substances added to food.  The other principal purpose, increasingly ignored by critics, was to avoid unnecessarily impeding innovation in the food supply.  In that respect, the GRAS exception has played a pivotal role, and its continuing utility should come as no surprise given the increasingly sophisticated analytical tools available to experts in the field of food toxicology.  The flexibility afforded by the GRAS exception is such that FDA relied on it with great success in developing its regulatory paradigm for bioengineered foods – a technological advance that certainly was not on the Congressional radar in 1958.  In summary, continued reliance on the GRAS exception is perfectly consistent with the twin purposes of the FAA, and has yielded the added benefit of enabling both industry and FDA to direct their food safety resources to areas where those resources can yield a greater return on investment – a significant benefit given the anticipated costs of implementing FSMA.

Another of the report’s central claims is that GRAS determinations are plagued with conflicts of interest because companies have a financial incentive to sell their products, and the fear of legal liability and damage to reputation are insufficient to counter that incentive.  In support of that contention, the report states:

The FDA has acknowledged that a company’s potential liability and its interest in protecting its brand are insufficient to ensure that food is safe.  In 2013 the agency said, “Because the demand for many manufactured or processed foods may not be sufficiently affected by safety considerations, incentives to invest in safety measures from farm to fork is diminished. Consequently, the market may not provide the incentives necessary for optimal food safety.”  “Even in cases where consumers are aware that their illness was contracted from a specific food,” the FDA explained, “it is often difficult to determine who is ultimately responsible for their illness, since the particular source of contamination is not known in many circumstances.”  It concluded that “it is unlikely that the existence of brands in the food sector creates the optimal level of safety for society.”

As a supporting reference, the report cites to FDA’s Preliminary Regulatory Impact Analysis for the Proposed Rules for Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food.  However, a review of that document reveals another inconvenient fact.  The quoted statements were made in the context of unintentional contamination of food.  In that context, it stands to reason that tracing an illness back to a specific product manufactured by a specific company is very challenging, and therefore the likelihood that the responsible company would be held accountable is diminished.  That logic does not apply in the context of the intentional use of an ingredient that is declared on a product’s label.  Indeed, NRDC had no difficulty identifying specific ingredients, products, and companies to target in its current report.

The relative ease with which a product can be identified is not the only factor that distinguishes the food ingredient context from the unintended contaminant context.  In the food ingredient context, FDA doesn’t have to show that the ingredient actually caused harm in order to challenge its use as an unapproved food additive; it is enough for FDA to show that general recognition of safety of the use of the ingredient is lacking.  The power of FDA’s enforcement tools in that context is amply demonstrated by some of the agency’s recent activities.  For example, FDA has issued warning letters to distributors of foods that contain melatonin (see here and here). The letters contend that FDA is unaware of any basis to conclude that the use of melatonin as a food ingredient is GRAS, and therefore the product in question is adulterated by virtue of containing an unapproved food additive.  FDA does not assert that the products in question actually caused injury because the agency doesn’t have to make that showing.

Similarly, when FDA announced its intent to investigate the safety of caffeine in food products, the mere expression of FDA’s concern was sufficient to prompt a number of companies to stop distribution.  That announcement followed on the heels of FDA’s prior warning letters targeting certain caffeinated alcoholic beverages, which the manufacturers subsequently stopped distributing.  These actions and industry’s response thereto give the lie to any claim that FDA’s ability to address potentially unlawful uses of food ingredients is hampered by the agency’s inability to show harm.  If anything, the challenge FDA faces in exercising its food additive authority lies in doing so judiciously, as illustrated by the agency’s recent, sweeping proposal to revoke the GRAS status of partially hydrogenated oils.

In closing out Part 1, we note that, whereas some critiques of the GRAS exception have been intended to enlighten, the current critique appears primarily intended to frighten.  The narrative is simple – profit-hungry companies are using unsafe chemicals in food to pump up their bottom lines, under the lazy eye of an agency that relies on outmoded science and an antiquated law.  While that narrative might provide a nice fund-raising platform for an NGO, it contributes little to the reasoned discourse needed to evaluate whether and how the existing system might be improved, and which improvements might yield benefits commensurate with their costs.  In that vein, we note that industry is stepping up to the plate with the establishment of a Center for Research on Ingredient Safety ("CRIS") in conjunction with Michigan State University.

By Riëtte van Laack –

In 2006, the American Beekeeping Federation and honey industry groups petitioned FDA (Docket No. FDA-2006-P-0207) to adopt a standard of identity for honey.  In 2011, FDA denied this petition because it concluded that no standard of identity was needed.  FDA asserted that existing enforcement tools could achieve petitioners’ goals. 

On April 9, 2014, FDA announced the availability of a draft guidance on the proper labeling of honey and honey products.  According to FDA, this draft guidance addresses the labeling issues relevant to the 2006 petition and reinforces existing laws and regulations to the industry.

FDA broadly defines honey as “a thick, sweet, syrupy substance that bees make as food from the nectar of flowers and store in honeycombs.”  The guidance does not address whether honey that has been subjected to ultrafiltration, removal of pollen, etc., qualifies as honey.  Instead it focuses on the labeling of honey with added sweeteners and other substances, and on the possible contamination with illegal pesticides.

The draft guidance includes a list of questions and answers including how and when to declare the floral source of honey, how to label products that contain honey and a sweetener, or honey and another ingredient such as natural flavors.

FDA notes that it has a “long-standing” import alert for surveillance of honey for adulteration with cane or corn sugars. The imported products are not admitted until FDA determines that they are not misbranded.

Although anyone can comment on any guidance at any time, to ensure that FDA receive and consider comments before finalizing the guidance, comments should be submitted by June 9, 2014.

By James C. Shehan –

The Generic Pharmaceuticals Association (“GPhA”) opened a new front in its ongoing battle to shape the approval process for biosimilars, while also calling for more cooperation between the US and the EU in their oversight of traditional generic drugs.  In a joint letter to the European Commission’s Trade Commissioner and the US Trade Representative, GPhA and the European Generic medicines Association (“EGA”) made recommendations that “regulatory convergence” be included in the negotiations for the Transatlantic Trade and Investment Partnership (“TTIP”).  TTIP is a prospective trade agreement that is currently being negotiated between the European Union and the United States.  It is intended to remove trade barriers in a wide range of economic sectors to make it easier to buy and sell goods and services between the EU and the US.

The GPhA/EGA letter makes five specific recommendations for inclusion in TTIP:

1. Implement a single development and approval pathway for biosimilars, via adoption of appropriate  guidelines/guidances by both regulators and facilitated by work of the existing FDA-EMA “cluster” group that currently exchanges information on biosimilars; 
2. Implement a single development and approval pathway for traditional generic medicines, again via adoption of appropriate  guidelines/guidances by both regulators and facilitated by establishment of a new FDA-EMA cluster that would meet regularly to exchange information; 
3. Mutually recognize cGMP inspections; 
4. Allow manufacturers to make generic and biosimilar products during the periods of US patent term extension and EU Supplementary Protection Certificates, so that (i) generic products made in the US and the EU can be exported for sale to the rest of the world prior to patent expiration and (ii) generic products can launch in the US and the EU immediately after patent expiration; and
5. Reject any suggestion to harmonize the US and EU  intellectual property regimes, specifically by rejecting any alignment of the periods of data and market exclusivity enjoyed by innovators.

It’s worth noting that in the context of TTIP, there is a difference between “convergence” and “harmonization.” Convergence refers to making separate systems work more smoothly together, while harmonization refers to adoption of the same system.  The European Commission’s website specifically notes that harmonization is “not on the agenda” for TTIP.  There may be some difficulties in squaring “no harmonization” with a “single development and approval pathway.”   

Interestingly, the GPhA/EGA letter is silent on one of most robustly debated biosimilar topics – how those products will be named in the US (see our previous posts here, here, and here).  Under the EU system, biosimilar products have names that are distinguishable from innovator reference product, either by use of a unique brand name or by attaching the company name to the generic name of the active ingredient.  GPhA has opposed proposals to require US biosimilars to have distinguishable nonproprietary names.  At a January meeting with FDA, however, GPhA, indicated that it may be willing to accept attaching a company name to the non-proprietary name, provided that the requirement also applies to brand name companies. GPhA also indicated at that meeting that its members would commit to the using brand names, even though FDA may not have the authority to require brand names.    

TTIP negotiators hope to finish their work in 2015.

By Kurt R. Karst –

When FDA announced on February 21, 2014 that the Agency would, upon finalization of a draft guidance document, reinterpret the New Chemical Entity (“NCE”) exclusivity provisions of the FDC Act to award NCE exclusivity for a newly approved Fixed-Dose Combination Drug (“FDC”) containing an NCE and a previously approved drug, FDA also issued a Consolidated Response denying the three Citizen Petitions submitted to the Agency in 2013 that led the Agency to its new interpretation in the first place.  Those petitions concerned STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058), PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution (Docket No. FDA-2013-P-0119), and NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471).  Now one of the petitioners – Gilead Sciences, Inc. (“Gilead”) – is asking FDA in a Petition for Reconsideration to rethink that decision with respect to STRIBILD, and to refuse to accept any ANDA or 505(b)(2) application for a drug product containing either of the two NCEs in STRIBILD – elvitegravir and cobicistat – under the rules governing NCE exclusivity.

As we previously reported, FDA decided to apply its new interpretation prospectively upon finalization of the draft guidance.  FDA explained in the Consolidated Response the Agency’s rationale for this decision and the bases for not granting the three petitions and awarding NCE exclusivity:

Exclusivity runs from the date of approval of a drug product.  At the time of approval of the drug products at issue here (i.e., Stribild, Natazia, and Prepopik), our existing interpretation of the relevant statutory and regulatory provisions was in effect.  We have decided not to recognize 5-year NCE exclusivity based on our new interpretation of these provisions, which we had not announced prior to the approval of these products . . . .

First, although the relevant statutory and regulatory provisions are ambiguous, our existing interpretation of these provisions is longstanding and has been consistently applied in many prior cases presenting similar facts.  Second, the new interpretation we are proposing represents a departure from our past interpretation, and we wish to avoid any unnecessary disruption to regulated industry.  Third, if the new interpretation were to be applied to products for which ANDAs already have been filed, it could impose a burden on the ANDA sponsors, who relied on our existing interpretation in filing their applications.

In addition, we do not believe that applying our new interpretation to the Petitioners’ products would advance the goals of the Hatch-Waxman Amendments.  Although we recognize that the Hatch-Waxman Amendments contain incentives to reward the development an approval of novel drugs, these particular products already have been developed and approved.  Recognizing additional exclusivity in this case is not necessary to encourage the development of novel drugs.  We believe that changing our interpretation going forward will foster Congress’s goal of encouraging the development and approval of novel drugs.  (Emphasis in original.)   

But according to Gilead, none of these reasons fit the circumstances surrounding STRIBILD.  First, with respect to FDA’s concern that recognizing NCE exclusivity would burden sponsors with pending applications, Gilead says that to its knowledge FDA has not yet even accepted an ANDA or 505(b)(2) application citing STRIBILD as the listed drug relied on for approval.  Second, as to FDA’s rationale that the STRIBILD approval was made when the “old” rules were (and still are) in effect, Gilead says that “the date of approval is not the relevant date . . . because FDA made the decision to defer the exclusivity determination for STRIBILD.”  Moreover, says Gilead, the company “raised the 5-year NCE exclusivity issues early during STRIBILD’s NDA process,” and “requested 5-year NCE exclusivity at the time of submission of the STRIBILD NDA and reiterated its request in a letter submitted to the agency immediately following STRIBILD’s approval.”  Third, FDA’s Hatch-Waxman goals remark misses the mark, says Gilead.  “Gilead developed the new active moieties in STRIBILD with the expectation that they would have 5-year NCE exclusivity,” writes the company.  The STRIBILD NDA was submitted to FDA before the NDAs for elvitegravir and cobicistat because “Gilead recognized during development that pursuing the combination product first would be more beneficial to patients and scientifically feasible.”  Finally, as to FDA’s comment that recognizing NCE exclusivity for an approved FDC would amount to “additional exclusivity,” Gilead says that “nothing additional or gratuitous is being requested,” and that “[a]warding the exclusivity in this instance represents the appropriate statutory recognition for having developed these novel drugs.” 

As to Gilead’s request that FDA refuse to accept any ANDA or 505(b)(2) application for a drug product containing either elvitegravir and cobicistat, the company argues that two key points of interpretation that predate the Consolidated Response require FDA to recognize NCE exclusivity for each active moiety. 

The statutory provisions governing NCE exclusivity – FDC Act § 505(j)(5)(F)(ii) (and its sister provision at Section 505(c)(3)(E)(ii)) – contain both an “eligibility clause” and a “bar clause.”  Under the “eligibility clause,” a drug is eligible for 5-year NCE exclusivity if it is “a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other [505(b)] application.”  Under the “bar clause,” the submission of any ANDA (or 505(b)(2) application) that “refers to the drug for which the [505(b)] application was submitted” is prevented for 5 years (absent a Paragraph IV certification).  Under FDA’s revised interpretation as described in the Consolidated Response, the term “drug” in the “eligibility clause” of the statute (and in the regulatory definition of NCE at 21 C.F.R. § 314.108) refers to drug substance, not drug product.  But what about the statutory “bar clause”?

According to Gilead, FDA agreed in the Consolidated Response that under the “bar clause” the term “the drug” has historically been interpreted under FDA’s so-called “umbrella policy” to mean a particular active moiety rather than a drug product.  Under that policy, described in various places in the preamble to the 1989 proposed regulations implementing the Hatch-Waxman Amendments, FDA interpretes NCE exclusivity:

to cover any subsequent approval of an application or supplemental application for a different ester, salt, or other noncovalent derivative, or a different dosage form, strength, route of administration, or new use of a drug product with the same active moiety.  Any modification to the product will be protected for the period of exclusivity remaining on the original application, unless the change occurs after or toward the end of the initial 5 years of exclusivity and independently qualifies for exclusivity under another exclusivity provision. [54 Fed. Reg. 28,872, 28,898-99 (July 10, 1989)]

“In light of that clear and appropriate interpretation, it is not plausible that the term ‘a drug’ in the [eligibility] clause . . . could mean something different,” says Gilead.  “Here, the meaning specifically adopted by the agency is that the ‘drug’ at issue in the exclusivity provision is a specific active moiety,” and not a drug product.

Furthermore, FDA long ago incorporated this active moiety-specific interpretation of the “bar clause” into the Agency’s implementing regulation at 21 C.F.R. § 314.108(b)(2), argues Gilead.  That regulation prevents for 5 years (absent a Paragraph IV certification) the submission of an ANDA or 505(b)(2) application that references “a drug product that contains a new chemical entity” (emphasis added).  “A drug product cannot ‘contain’  another drug product; it may contain drug substances and moieties, but not other drug products.”  Thus, argues Gilead, FDA’s bar regulation “is designed to provide the same scope of protection – namely, moiety-specific protection – as the bar clause in the statute, based on FDA’s clear and reasonable interpretation of the statute.”

By Riëtte van Laack –

Does the same standard that applies when regulators require label statements that “correct a deception,” such as false advertising, also apply when they require label statements for other purposes based on the interests of the government?  This issue will be before the United States Court of Appeals for the District of Columbia Circuit (“D.C. Circuit”) en banc in the rehearing of the appeal by American Meat Institute and others (“AMI”) challenging the U.S. Department of Agriculture’s (“USDA’s”) regulations requiring mandatory country of origin labeling (“COOL”) statements.  (See our previous posts here, here, and here.) 

AMI had argued that the government does not have a good enough reason to override the industry’s free speech rights and force them to make statements against their will.  According to AMI, the more demanding test of Central Hudson Gas & Electric v. PSC of New York, 447 U.S.56 (1980) ought to apply rather than the lesser standard of Zauderer v. Office of Disciplinary Counsel, 471 U.S. 626, 651 (1985), because the COOL regulation was not an anti-deception regulation.  Under Zauderer, a commercial speaker has only a minimal First Amendment interest in not providing purely factual information with which it does not disagree, as long as the mandatory disclosure is reasonably related to the state’s interest in preventing or correcting deception.  The three judge panel of the D.C. Circuit, in a unanimous decision decided to follow other circuits that held that the Zauderer standard applies to more than disclosures that correct deception.  For example, in reaching its decision, the panel noted that the Second Circuit had extended it to “government interests in telling buyers that mercury-containing light bulbs do contain mercury and may not be disposed of until steps have been taken to ‘ensure that [the mercury] does not become part of solid waste or wastewater.’” The Court determined that previous D.C. Circuit decisions that AMI cited in its favor did not apply because those cases did not involve purely factual and uncontroversial information.  However, in a footnote it suggested that the full court hear the case en banc to provide a clear ruling on the issue.

Rehearings en banc are relatively rare.  The D.C. Circuit’s Handbook of Practice and Internal Procedures notes “Federal Rule of Appellate Procedure 35(a) expressly states that en banc hearings are not favored and ordinarily will not be ordered except to secure or maintain uniformity of decisions among the panels of the Court, or to decide questions of exceptional importance.”  Under the Circuit procedures, “[t]he Court sitting en banc consists of all active judges, plus any senior judges of the Court who were members of the original panel and wish to participate.”  Of the court’s senior Judges, only Judge Williams was a member of the original panel. 

On April 4, 2014, the D.C. Circuit issued an order setting the case for rehearing en banc.  Parties are to file supplemental briefs by April 21, 2014 addressing “[w]hether, under the First Amendment, judicial review of mandatory disclosure of ‘purely factual and uncontroversial’ commercial information, compelled for reasons other than preventing deception, can properly proceed under Zauderer . . . or whether such compelled disclosure is subject to review under Central Hudson.”  Oral argument before the en banc court is scheduled for 9:30 a.m. on Monday, May 19, 2014.

By Kurt R. Karst –    

Shortly after Massachusetts Governor Deval Patrick issued a press release on March 27, 2014 announcing a Declaration of Emergency and that the Governor had directed the Massachusetts Department of Public Health (“DPH”) and its Commissioner, Cheryl Bartlett, RN, to take several actions to combat opioid overdose, including granting DPH “emergency powers” to, among other things, ban the prescribing and dispensing of ZOHYDRO ER (hydrocodone bitartrate) Extended-release Capsules, rumors began to swirl that the manufacturer of the drug, Zogenix, Inc. (“Zogenix”), would take legal action.  Those rumors intensified when later on March 27, 2014 the DPH Commissioner Bartlett and the Public Health Council approved an Emergency Order stating: “No registered individual practitioner shall prescribe or order, and no one shall dispense or administer any hydrocodone bitartrate product in hydrocodone-only extended-release formulation until the Commissioner has determined that adequate measures are in place to safeguard against the potential for diversion, overdose and abuse.” 

Less than two weeks after Governor Patrick’s announcement, and now that other states are considering (or taking) similar action (e.g., Vermont recently issued an emergency rule that will reportedly make it more difficult for physicians to prescribe the drug within state limits), Zogenix is taking a stand.  Earlier this week, Zogenix filed a Complaint and a Motion for Temporary Restraining Order and Preliminary Injunction in the U.S. District Court for the District of Massachusetts alleging that the Commonwealth’s ban on ZOHYDRO ER is unconstitutional because the ban violates the Supremacy Clause, the dormant Commerce Clause, and the federal Contracts Clause of the U.S. Constitution:

To put it in plain terms: the Order banning Zohydro™ ER is unconstitutional.

To begin with, it is preempted by federal law.  FDA, not Governor Patrick and not the State DPH, has the authority to approve new drugs, to determine the formulations that are safe and effective for use, and to authorize their introduction into the interstate market.  And after extensive consideration, FDA approved Zohydro™ ER in its current formulation, finding it safe and effective for use in treating patients with chronic pain for whom their physicians conclude Zohydro™ ER is indicated.  Neither Governor Patrick nor the state DPH has the authority or the ability to countermand that determination and declare Zohydro™ ER unsafe in its current formulation.  The Order also runs afoul of the dormant Commerce Clause, which prohibits a state from taking a regulatory action that has impact outside its borders, or if which replicated would result in the effective dismantlement of a national regulatory scheme.  And it violates the federal Contracts Clause, because the Order undoes private contracts between Zogenix and other contracting parties for services in Massachusetts, all without sufficient justification. 

FDA approved ZOHYDRO ER on October 25, 2013 under NDA No. 202880 after an extended review cycle for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.  ZOHYDRO ER is manufactured without an abuse-deterrent formulation, and that fact has made the approval controversial.  Indeed, several members of Congress have sent letters to FDA protesting the approval, and legislation has been introduced to withdraw the NDA approval (S. 2134 and H.R. 4241).  Nevertheless, ZOHYDRO ER remains an approved medication.  And as Zogenix points out in its lawsuit:

In rendering a considered decision that the benefits of Zohydro™ ER outweighed the drug’s potential risks, the FDA satisfied Congress’s dual mandate of promoting and protecting public health by classifying Zohydro™ ER as “safe and effective,” consistent with its obligations under 21 U.S.C. § 393(b)(2)(B).  That determination reflects the FDA’s expert conclusion that public access to the drug “promote[s]” the public health.

Thus, Zogenix argues that the Commonwealth’s ban on ZOHYDRO ER:

stands as an impermissible obstacle, in two ways, to the FDA’s mandate to make particularized drug approvals for the protection and promotion of the public health.  First, . . . state drug prohibition decisions contrary to those of the FDA – such as the Massachusetts ban here – would harmfully undermine the authoritative character of federal safety decisions designed to have national effect. . . .  Second, the Massachusetts order plainly conflicts with the scientific predicates supporting the FDA’s approval of the same drug Massachusetts wants banned – and thus with Congress’ objective to promote public health by facilitating access to important treatments.

Zogenix is seeking, among other things, declaratory and injunctive relief.  Specifically, Zogenix seeks a declaration that Governor Patrick’s and DPH Commissioner Bartlett’s conduct in effectuating a ban on ZOHYDRO ER violates the U.S. Constitution, and final order enjoining Massachusetts from implementing or enforcing the Declaration of Emergency, the Emergency Order (or any other action banning the prescription, ordering, dispensing, and administration of ZOHYDRO ER), or an order vacating those actions.  A hearing was held on April 8th regarding Zogenix's Motion for Temporary Restraining Order and Preliminary Injunction.  Judge Rya W. Zobel granted a continuance to allow the parties some additional time.  A hearing is now scheduled for April 14th at 9:00 AM.

Massachusetts’ action banning ZOHYDRO ER, and Zogenix’s response to that action, seems to be a case of first impression.  We’re not aware of another lawsuit like it.  A decision in favor of the Commonwealth could set the stage for future state action against particular drug products, and could undermine FDA’s drug approval authority.  During the April 8th hearing, however, Judge Zobel reportedly indicated that she will likely strike down the ban, presumably on preemption grounds. 

By Jennifer M. Thomas & James P. Ellison –

Hyman, Phelps & McNamara, P.C. (HP&M) filed comments on April 7 concerning FDA’s Guidance document, Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND (the “Guidance”).  HP&M has previously blogged on this Guidance (here, here, here, and here).

HP&M’s comments on the Guidance focus on the legal issues that the Guidance raises.  Most important, through the Guidance FDA seeks to impose on food, medical food, dietary supplement and cosmetics the same pre-study requirements that the law properly authorizes for drug studies.  However, FDA has no legal authority to impose these requirements on non-drug studies, as HP&M’s comments make clear.  The negative public health impacts of FDA’s unauthorized Guidance, while not the primary focus of these comments, would be profound.  HP&M’s comments point out that the only appropriate solution is for FDA to remove references to foods and cosmetics from the Guidance and to revise the Guidance to make it consistent with the authority granted to FDA under the Federal Food, Drug, and Cosmetic Act.

Spring is here!  How do we know?  Is it the cherry blossoms in peak bloom in Washington, DC?  Is it the daffodils emerging from hibernation?  No – we know it’s Spring because the annual American Conference Institute (“ACI”) “Paragraph IV Disputes” conference is right around the corner. 

That’s right, ACI will be holding its 8th annual “Paragraph IV Disputes” conference from April 28-29, 2014 at the Conrad New York in New York City.  The 2014 conference is a special one with the 30th Anniversary of the Hatch-Waxman Amendments later this year (September 24, 2014).  Attendees will get to hear from a virtual “who’s who” of Hatch-Waxman litigators and industry decision makers.  Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst will be speaking at a session assessing implementation of the Generic Drug User Fee Amendments and other recent developments that affect Paragraph IV litigation.

FDA Law Blog is a conference media partner.  As such, we can offer our readers a special $200 discount off the current price tier.  The discount code is: FDA200.  You can access the conference brochure and sign up for the event here.  We look forward to seeing you at the conference.  

The American Bar Association’s Section of Ligation (specifically the Food and Supplements Subcommittee of the Products Liability Committee) just announced its Fourth Annual Food & Supplements Workshop, scheduled for June 5 in the Minneapolis area.  Among the topics to be addressed:

• Emerging Issues: Surveying the Regulatory and Litigation Horizon
• Ethical Issues Arising from Governmental Investigations and Potential Criminal Charges Under the Park Doctrine
• FSMA New Developments
• Consumer Fraud Class Actions—Litigation and Settlement Strategy
• Anatomy of a Recall
• Litigation Risks: How In-House and Outside Counsel Can Work Together to Identify and Preemptively Address Potential Lawsuits Targeting Food and Supplement Products

Hyman, Phelps & McNamara, P.C.’s Ricardo Carvajal will participate in discussion of key issues raised by the latest proposed regulations issued under the authority of the Food Safety Modernization Act.  Additional information and a link to registration are available here.  

By Karla L. Palmer –

The Energy and Commerce Committee’s Subcommittee on Health (chaired by Representative Joe Pitts (R-PA)), has scheduled a hearing for Monday, April 7, 2014, at 3:00 p.m. in room 2123 of the Rayburn House Office Building.

The hearing is titled “Improving Predictability and Transparency in DEA and FDA Regulation.” Industry and government witnesses include, among others, Janet Woodcock, M.D. (Director CDER, FDA), Mr. Joseph T. Rannazzisi (Deputy Assistant Administrator, Office of Diversion Control, DEA);  Dr. Nathan B. Fountain (Chair, Medical Advisory Board, Epilepsy Foundation), and Mr. John M. Gray (President and CEO, HDMA).

Subcommittee members will review three bills described below: H.R. 4299, “Improving Regulatory Transparency for New Medical Therapies Act,”; H.R. 4069, “Ensuring Patient Access and Effective Drug Enforcement Act;” and H.R. 4250, the “Sunscreen Innovation Act”.

H.R. 4299, blogged about here, would amend the CSA to improve efficiency of the DEA’s process for scheduling new drugs approved by the FDA. Introduced by Representative Pitts (R-PA) and Ranking Subcommittee Member Frank Pallone (D-NJ), the bill would require DEA to make a final determination within 45 days after receiving FDA’s scheduling recommendation for a new drug.  Additionally, it would generate more transparency in the drug application process for clinical trials by requiring that DEA make a final determination within 180 days or provide the applicant with details about what outstanding issues remain unresolved.

H.R. 4069, introduced by Vice Chairman Marsha Blackburn (R-TN), Rep. Tom Marino (R-PA), would improve enforcement efforts regarding controlled substance drug diversion and abuse.  The legislation would help prevent controlled substance abuse and diversion, yet ensure patient access to necessary medications by creating a collaborative partnership between drug manufacturers, wholesalers, retail pharmacies and federal enforcement and oversight agencies.  

The bill also seeks to better define standards set forth in the CSA including the definition of “consistent with the public health and safety” as having a “substantial relationship” to the CSA’s “purpose of preventing diversion and abuse of controlled substances.”  In addition, the legislation would further define “imminent danger” as meaning “a significant and present risk of death or serious bodily harm that is more likely than not to occur in the absence of an immediate suspension order.” (Emphasis added.)   This enhanced definition of “imminent danger” may be a fallout from DEA decisions to issue immediate suspension orders against at least two drug distributors and at least one nationwide retail pharmacy in the past few years where the subject of those immediate suspension orders involved conduct that occurred — and typically had resolved – well prior to DEA’s serving of the immediate suspension orders, causing the parties to challenge the DEA’s definition and interpretation of what constitutes “imminent danger.” 

The legislation would also require employers (specifically distributors and manufacturers of schedule I though V drugs)  to obtain as a condition of the registration criminal background checks and drug testing for employees with access to controlled substances. The employee background checks must be obtained periodically (not more frequently than every two years) and at the time of hiring (if hired after the date of the enactment of the legislation). Those that fail to comply with the background check provision would be subject to civil penalties. 

The legislation would also permit registrants the opportunity to submit a corrective action plan prior to revocation or suspension of a registration under 21 U.S.C. § 824(c).  Specifically the amendment would require the DEA to provide notice to the registrant of the grounds for revocation or suspension including the citation to specific violations, and give the registrant an opportunity to submit a corrective plan within a reasonable period of time to demonstrate how the registrant plans to correct the grounds for revocation or suspension.  The DEA would then make a determination whether in light of the plan, revocation or suspension proceedings should be discontinued or deferred or additional changes need to be made to the corrective plan. 

Finally, the legislation would also establish the “Combat Prescription Drug Abuse Working Group” to include not more than 20 members (pharmacy, patient groups, manufactures, distributors, hospitals and health care providers, law enforcement, DEA representatives, states attorneys general representatives, and public policy experts, among others).  The (non-paid) Working Group members would, among other things, review and report to Congress on efforts to reduce prescription drug abuse and diversion, examine recommendations for transfer of controlled substances between schedules, and make specific recommendations to reduce diversion and abuse of prescription drugs.  The Working Group would also be responsible for various reports and recommendations for FDA, DEA and various other federal and state agencies on several topics identified in the legislation. 

H.R. 4205, introduced by Representative Ed Whitfield (R-KY) and Rep. John Dingell (D-MI), would expedite the FDA’s approval process for new sunscreen ingredients while maintaining strict safety standards. The FDA has not approved a new sunscreen ingredient in almost two decades. As we previously reported, the legislation would attempt to streamline the drug approval process for sunscreens and provide transparency – through regular reports to Congress. The legislation would require that pending applications are completed within eight months and that new applications reviewed within 11 months.

By John A. Gilbert, Jr. – 

A new bill introduced in Congress, H.R. 4299 (titled “Improving Regulatory Transparency for New Medical Therapies Act”), would significantly streamline the drug scheduling process for new medical therapies and reduce the potential for unnecessary delays in the availability of these needed medicines.  The bill would also require the Drug Enforcement Administration (“DEA” or “Agency”) to make a decision on new registration applications for the manufacturing and distribution of drugs and substances used in clinical trials.  A hearing on the bill is scheduled before the House Energy and Commerce Committee on April 7, 2014.   

As reported here and here, the recent example of the long delay in DEA’s scheduling of Eisai’s FYCOMPA (perampanel) – more than a year after it was approved for marketing by the FDA – highlights the need for a change in the process.  The bill would amend the Controlled Substances Act (“CSA”) to require DEA to issue an interim final scheduling rule within 45 days of receiving a recommendation from the Department of Health and Human Services (“HHS”) to schedule a new drug or substance not previously marketed or scheduled in the United States.  The bill would require DEA to take such action pursuant to the “good cause” exception to issuing a notice of proposed rulemaking under the Administrative Procedures Act (5 U.S.C. § 553(b)(3)(B)).  The interim final rule would be made immediately effective pursuant to 5 U.S.C. § 553(d)(3).

As we discussed previously, scheduling based on the HHS recommendation is reasonable and rational for a new medicine where the drug has not been marketed in the United States and thus there is no actual abuse data available.  Under such circumstances, the HHS and FDA scientific and medical review of the drug is the best source of abuse potential, so scheduling a new drug on this basis is consistent with the public interest.  It also avoids the issue previously reported where Eiasi faced losing a significant period of its patent exclusivity solely because it had to await DEA’s scheduling notice for the newly approved drug.

The bill would also amend the CSA to put a time limit on DEA’s review of an application for a DEA registration to be used only for the manufacture or distribution of a controlled substance for clinical trials.  The DEA would be required to make a decision within 180 days of receiving the application.  If the Agency does not make a decision on the application within this time, the Agency would have to give written notice to the applicant as to any outstanding issues that must be resolved in order to make a final decision on the application and the estimated date on which a decision would be made. 

Neither the CSA nor DEA regulations currently impose any time limits on DEA to decide on whether to grant or deny new applications for any DEA registration.  Imposing such time limits could be beneficial to all applicants – not just manufacturers or distributors for use in clinical trials.  We would like to see such limits imposed on all DEA applications for registration; not just in the narrow context expressed in the bill.  There are some obstacles where the 180-day time limit may be difficult, e.g., where DEA is required to publish a notice in the Federal Register for applications for bulk manufacturing of narcotic drugs; however, in most cases requiring DEA to act on an application within, for example, six months would not likely be an unreasonable burden on the Agency.

By Kurt R. Karst –      

In a 17-count, 84-page Complaint filed earlier this week in the U.S. District Court for the District of New Jersey, Mylan Pharmaceuticals Inc. (“Mylan”) alleges that Celgene Corporation (“Celgene”) has violated federal and state antitrust laws by preventing generic competition for Celgene’s drug products, THALOMID (thalidomide) Capsules and REVLIMID (lenalidomide) Capsules.  Both drug products are the subject of a Risk Evaluation and Mitigation Strategies (“REMS”) – here and here – providing for restricted distribution of the products because of safety concerns – a so-called ETASU (Elements To Assure Safe Use) REMS.  

According to Mylan:

Celgene, a branded drug manufacturer, has used REMS as a pretext to prevent Mylan from acquiring the necessary samples to conduct bioequivalence studies, even after the FDA determined that Mylan’s safety protocols were acceptable to conduct those studies.  In furtherance of its scheme to monopolize and restrain trade, Celgene implemented certain distribution restrictions that significantly limit drug product availability.  Indeed, Mylan had contacted known wholesale distributors throughout the years, in an effort to obtain Thalomid and Revlimid samples, however, those efforts were unsuccessful.  Throughout this entire period, Celgene has engaged in a scheme . . . to continuously prevent and/or stall all of Mylan’s efforts to obtain samples of Thalomid and Revlimid.  In so doing, Celgene prevented Mylan from obtaining any of the drug products necessary to conduct required bioequivalence testing.

Among other things, Mylan is seeking preliminary and permanent mandatory injunctive relief to compel Celgene to sell Mylan sufficient quantities of THALOMID and REVLIMID at market prices for purposes of bioequivalence testing and ANDA submission, and compensatory damages for Mylan’s lost sales of generic THALOMID and REVLIMID (and profits on those sales) determined to be caused by the delay in Mylan’s ability to submit an ANDA to FDA.

Issues concerning ETASU REMS, restricted distribution programs, and generic competition have previously been debated in court.  As we previously reported, in September 2012, Actelion Pharmaceuticals Ltd. and Actelion Clinical Research, Inc. preemptively sued prospective ANDA applicants Apotex Corp. and Roxane Laboratories, Inc. in a Complaint filed in the U.S. District Court for the District of New Jersey seeking declaratory relief that Actelion is under no duty or obligation to supply ANDA applicants with TRACLEER (bosentan) Tablets, approved with an ETASU REMS, for purposes of bioequivalence testing and ANDA submission.  That lawsuit was ultimately dismissed after a settlement between the parties, but not before the Federal Trade Commission filed an amicus brief in the case (see our previous post here) asking the court to “carefully consider the unique regulatory framework governing the pharmaceutical industry and the potential ramifications for consumers of prescription drugs.”

Another lawsuit going back to early 2008 brought by Lannett Company, Inc. against Celgene involving THALOMID, restricted distribution, and generic competition issues was also dismissed after a settlement between the parties.  (See our previous post here.)

By William T. Koustas –

FDA has begun its efforts to implement the Drug Supply Chain Security Act (“DSCSA”), also known as Title II of the Drug Quality and Security Act.  As we have reported in prior posts (here and here), the DSCSA requires FDA to issue a series of guidance documents and hold public meetings with respect to the exchange of transaction information, transaction history, and transaction statements (“TI/TH/TS”), the serialization of prescription drug products, and the handling of suspect or illegitimate prescription drugs.  FDA took a first step in that direction in February, when it issued a call to pharmaceutical supply chain stakeholders for their comments with respect to these issues.  In a Federal Register notice, 79 Fed. Reg. 9745 (Feb. 20, 2014), FDA asked stakeholders and interested parties to provide comments on: (1) their current practices and ideas for the interoperable exchange of TI/TH/TS in paper and electronic format; (2) the feasibility of establishing standardized documents to facilitate the exchange of TI/TH/TS; and (3) current practices and ideas on the exchange of information between supply chain members and FDA with respect to verification requests and notifications for suspect or illegitimate drug products.  The federal register notice includes several questions in these areas to which stakeholders can respond or they can submit general comments with respect to these topics.  Comments are due by April 21, 2014.

On April 2, 2014, FDA issued a notice for a public workshop titled, “Standards for the Interoperable Exchange of Information for Tracing of Human, Finished Prescription Drugs, in Paper or Electronic Format,” 79 Fed. Reg. 18562 (April 2, 2014).  The purpose of this workshop, which will be held May 8th and 9th at FDA’s White Oak Campus, is to provide an opportunity for interested parties to share information on current practices, research, and ideas regarding the feasibility of creating standardized TI/TH/TS documents.  FDA notes that it is particularly interested in using the workshop to learn about current practices, processes, and systems stakeholders use to exchange information as well as how trading partners could respond to verification requests and notifications as required by the DSCSA.  People interested in attending this workshop must register by April 24, 2014.  FDA is also accepting comments regarding the workshop until June 9, 2014.     

FDA has also created a website that summarizes the implementation timeframes created by the DSCSA.  These timeframes are currently based on statutory deadlines, but FDA indicated that it will “update” this website as appropriate. 

By Kurt R. Karst –       

Earlier this week, Celltrion Healthcare Co., Ltd. and Celltrion, Inc. (collectively “Celltrion”) filed a Complaint for Declaratory Judgment in the U.S. District Court for the District of Massachusetts seeking a judgment with respect to certain patents allegedly covering Janssen Biotech, Inc.’s (“Janssen’s”) biological product REMICADE.  The Complaint marks the beginning of the second lawsuit that will undoubetedly bring into play the complex patent resolution provisions added to the PHS Act by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”).  The BPCIA created a pathway for the submission and approval of biosimilar versions of brand-name reference products under a so-called Section 351(k) application. 

In November 2013, in Sandoz, Inc. v. Amgen, Inc. and Hoffman-La Roche, Inc., the U.S. District Court for the Northern District of California granted Amgen Inc.’s and Hoffmann-La Roche Inc.’s Motion to Dismiss a June 2013 Complaint for Declaratory Judgment and Patent Invalidity and Non-infringement concerning two patents Roche licensed to Amgen that purportedly cover Amgen’s biological product ENBREL (etanercept).  According to the district court, “Sandoz does not contend, and cannot contend, it has complied with its obligations under [PHS Act §§ 351(l)(2)-(6)], because . . . it has not, to date, filed an application with the FDA.”  The reference to PHS Act §§ 351(l)(2)-(6) is to the BPCIA’s multi-step “patent dance” procedures: Step 1 – Transmission of Biosimilar Application; Step 2 – Reference Product Sponsor’s Paragraph 3(A) Patent List; Step 3 – Biosimilar Applicant’s Paragraph 3(B) Patent List; Step 4 – Reference Product Sponsor’s Response; Step 5 – Patent Resolution Negotiations; Step 6 – Patent Resolution If No Agreement; and Step 7 – Filing of the Patent Infringement Action. 

As we previously reported, Sandoz appealed the district court decision to the U.S. Court of Appeals for the Federal Circuit (Docket No. 14-1693).  In March, Sandoz filed its Opening Brief in the appeal.  According to Sandoz, the district court’s decision “completely deprives federal courts of jurisdiction over any declaratory judgment action implicating a biosimilar product until after the FDA had already approved the product—a serious error that undermines the BPCIA’s stated purpose of advancing competition for biologic drugs.”  Moreover, says Sandoz, the court’s belief that it lacked jurisdiction because Amgen did not specifically threaten to sue Sandoz for patent infringement is directly contrary to the U.S. Supreme Court’s holding in MedImmune, Inc. v. Genentech, Inc., 549 U.S. 118 (2007), which the district court did not cite in its decision.  Sandoz continues in its brief with some interesting arguments and thoughts:

The district court’s contrary ruling defies both the plain text and very purpose of the BPCIA.  The BPCIA contains no provision depriving courts of jurisdiction to resolve patent disputes where jurisdiction already existed, as here, before an FDA filing.  While the BPCIA does contain certain limitations on declaratory judgment actions after a biosimilar application is submitted, those limitations do not apply to Sandoz’s complaint, which was filed before any FDA application.  The district court was not at liberty to impose a jurisdictional bar that does not exist in the statute’s text, and its decision to create such a bar—without briefing on the issue, no less—was pure error.

The district court compounded this error by misinterpreting the BPCIA’s provisions.  According to the district court, “neither a reference product sponsor, such as Amgen, nor an applicant, such as Sandoz, may file a lawsuit unless and until they have engaged in a series of statutorily-mandated exchanges of information.”  But those patent exchanges serve only as a prelude for an action for a patent owner’s infringement lawsuit under § 271(e)(2)(C), not a declaratory judgment.  The statute allows either party to file for declaratory judgment once a biosimilar applicant gives notice of its intention to market its product.  Thus, even if the BPCIA applied, as the district court found, its provisions would expressly permit Sandoz’s action here because Sandoz provided Amgen notice of its intention to commercially market its product before bringing this case. . . . 

The district court’s judgment also seriously disrupts the exclusivity structure of the BPCIA.  According to the statute, the biosimilar applicant must give at least six months’ notice before launching its product.  If a biosimilar applicant is forbidden from providing this notice before its approval—as the district court now holds—then applicants will be forbidden from launching biosimilar products until six months after obtaining final FDA authority to do so, in all cases, and regardless of any existing patent coverage or the expiry of the 12-year data exclusivity period.  The court’s erroneous construction thereby guarantees every biosimilar product must uselessly wait to launch for six months after the FDA provides formal approval to launch, creating an extra-statutory period of product exclusivity that Congress never intended in drafting the BPCIA. [(Emphasis in original; internal citation omitted.)]

We won’t be surprised if we see some of these same arguments made in the new Celltrion case, which we assume also involves a product that will be the subject of a Section 351(k) biosimilar application. 

Celltrion’s product REMSIMA, which is reportedly approved in 47 countries and is pending approval in another 23 countries, is intended as a biosimilar version of REMICADE.  REMICADE is a blockbuster product that FDA first approved in August 1998 under BLA No. 103772.  It is currently approved for treating myriad diseases and conditions: rheumatoid arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. 

According to Celltrion, the company “intends to apply for marketing approval of Remsima® in the United States during the first half of 2014,” and expects FDA approval “by early 2015 (assuming the approval process is not hindered by interference from Janssen or its affiliates).”  That means Celltrion is very close to submiting a Section 351(k) biosimilar application to FDA.  Indeed, the company says that it has “scheduled a final meeting with the FDA to discuss the format and content of Celltrion’s regulatory application.”

To clear the patent thicket and a path to marketing its biosimilar version of REMICADE, Celltrion says that it is necessary to obtain a declaratory judgment that certain patents applicable to REMICADE – U.S. Patent Nos. 5,919,452, 6,284,471, and 7,223,396 – are invalid and unenforceable.  According to Celltrion:

Janssen and its predecessors originally applied for patents relating to Remicade® in 1991, and obtained its first patent in 1997.  Under U.S. law, Janssen’s period of permissible patent protection should have already ended.  However, Janssen and its predecessors are trying to improperly extend its monopoly after its initial patents expired.  Janssen holds at least three U.S. patents. . . that will purportedly cover Remicade® beyond 2014. . . .  Celltrion is informed and believes that Janssen and its predecessors and affiliates have engaged in manipulative and deceptive practices before the U.S. Patent & Trademark Office to improperly extend the length of its patent monopoly for Remicade®, and to obtain patents the Patent Office never would have issued had it known all material facts.

Why initiate litigation now instead of after the filing of a Section 351(k) biosimilar application?  According to Celltrion:

Because Celltrion expects to face patent infringement allegations from Janssen, Celltrion wants to start the adjudicative process regarding the invalidity and unenforceability of Janssen’s patents.  This will enable Celltrion to immediately avail itself of the processes available in the federal judiciary to discover information relating to Janssen’s patents, to learn Janssen’s claim constructions and infringement contentions, and to present issues speedily for adjudication and test the validity and enforceability of Janssen’s patents.

And if Celltrion is unable to challenge the patents now, what then?  According to the company, it “would delay Celltrion’s access to the judicial system for about 10‐12 months (and perhaps even longer),” which “could force Celltrion into a difficult choice between (a) launching Remsima® without the benefit of discoverable information regarding Janssen’s patents and legal positions, or (b) not launching Remsima® at the earliest opportunity and waiting for a delayed legal process to play out.”  

We’re keeping a close eye on both the Sandoz and Celltrion cases because the decisions in these cases will undoubetedly set the stage for the implementation (and success or failure) of the BPCIA for years to come.