By Jeffrey N. Wasserstein –

Loyal readers of the FDA Law Blog have followed (with bated breath) the saga of Vermont’s law that prohibits pharmaceutical and medical device companies from giving many items that are permitted under the PhRMA Code and AdvaMed Code.  The plot has thickened even further with the recent passage of S. 88, which became law on May 27, 2010, albeit without the governor’s signature (he objected to some of the very provisions we’ll be discussing below). 

Most notably, the bill amends the existing law to provide that samples that may be given to patients include not only prescription items, but also over-the-counter drugs, nonprescription medical devices, or items of nonprescription durable medical equipment.  Nota bene:  “Sample” was also defined to include “starter packs and coupons or other vouchers that enable an individual to receive a prescribed product free of charge or at a discounted price.”  While permissible, the kicker here is that beginning on or before April Fools’ Day 2012, companies must disclose all samples that have been disseminated in Vermont during the prior calendar year, identifying for each sample the product, recipient, number of units, and dosage.  While pharmaceutical companies already track samples for purposes of compliance with the PDMA sample tracking requirements, the Vermont requirement also applies to coupons and vouchers for free or discounted prescription products, OTC products and nonprescription devices and DME which are not currently tracked.

The Vermont law does not apply by its terms to any samples required to be reported under the Patient Protection and Affordable Care Act of 2010 (a/k/a Healthcare Reform), which we summarized here, as long as the Vermont Attorney General determines that the U.S. Department of Health and Human Services ("HHS") will collect and report state- and recipient-specific information regarding samples.  How this will play out, remains to be seen. 

On the bright side, we have seen at various booths throughout the country at professional meetings and conferences signs that say “Dogs and Vermont Physicians Need Not Apply for Coffee”.  (Ok, we exaggerate slightly, but see below.) 

The new law clarifies that the provision of coffee or other snacks or refreshments at a booth at a conference or seminar is permitted, and does not even need to be reported!  Barristas from Bennington to Newport rejoice!

Other notable changes include permitting companies to provide grants for fellowship salary support, provided the manufacturer is completely hands-off, including that the institution requesting the grant selects the fellows, the manufacturer imposes no demands or limits on the use of the funds, and (demonstrating that Vermont doesn’t quite understand why companies might want to fund such fellowships), the fellowship cannot be named for the sponsoring manufacturer.  The law also clarifies that companies may sponsor continuing medical education programs and the sponsor may, in its discretion, use such funding to provide for meals and other food at the conference.  There was some  confusion prior to this law as to the permissibility of funding for CME where the CME provider used the funding for meals.  Clarity achieved!  Fund away!

We kid because we care.  As we noted in one of our prior posts on Vermont, states are free to experiment.  At some point, the experimentation goes too far.  As noted by the Governor of Vermont in his statement explaining why he was refusing to sign the bill and was allowing it to become law without his signature, “physicians, non-profits and other organizations across Vermont have expressed significant concern about the chilling effect certain provisions could have on the ability of low-income Vermonters to receive free samples of vital prescription drugs.”  At some point, companies will weigh the cost of doing business in Vermont and decide that it isn’t worth it.  Or, they will do business and decide it’s not worth providing coupons, vouchers or samples to physicians in Vermont, thereby avoiding the hassle of reporting to the Vermont Attorney General.  That cannot be good for Vermont patients, as noted by Governor Jim Douglas.  But at least we know companies can give Vermont MDs a cup of joe at the next professional meeting.

By Kurt R. Karst –   

FDA's recent approval of an ANDA submitted by Perrigo R&D Company ("Perrigo") for a generic version of the over-the-counter drug MONISTAT 1 Combination Pack (1200 mg miconazole nitrate vaginal insert and 2% miconazole nitrate cream) contains some interesting language concerning 180-day exclusivity eligibility.  It it the latest type of post-Medicare Modernization Act ("MMA") 180-day exclusivity "punt" language adopted by FDA. 
 
As we previously reported, FDA has, on several occasions punted on the issue of post-MMA 180-day exclusivity eligibility.  Those punts have come up in the context of 180-day exclusivity forfeiture under FDC Act § 505(j)(5)(D)(i)(IV), where a company failed to obtain tentative ANDA approval within 30-months of application submission.  In each of those cases, FDA did not make a formal forfeiture determination at the time of ANDA approval and stated it would do so only if another applicant becomes eligible for approval within 180 days after exclusivity is triggered.
 
The latest punt comes under the failure-to-market forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I), which provide that 180-day exclusivity is forfeited based on the "later of" two dates: (1) the earlier of 75 days after ANDA approval or 30 months after ANDA submission; and (2) 75 days after which "[t]he patent information submitted under [FDC Act § 505(b) or (c)] is withdrawn by the holder of the" NDA holder (FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC)), among two other litigation-related events (FDC Act § 505(j)(5)(D)(i)(I)(bb)(AA) & (BB)).  In March 2010, the U.S. Court of Appeals for the District of Columbia Circuit ruled in Teva Pharms USA, Inc. v. Sebelius, 595 F.3d 1303 (D.C. Cir. 2010), that Teva did no forfeit 180-day exclusivity eligibility under the failure-to-market forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I), and FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC) in particular.  In doing so, the Court reasoned that the patent delisting counterclaim provision at FDC Act § 505(j)(5)(C)(ii)(I) added by the MMA must be read together with the patent delisting forfeiture provision at FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), and that FDA's broad reading of FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), in which the Agency interpreted the provision such that the mere request to withdraw patent information from the Orange Book is a forfeiture event under FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), was not sustainable.  FDA has been reluctant to adopt a narrow interpretation of FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), but has done so nevertheless. 
 
MONISTAT 1 Combination Pack is listed in the Orange Book with two patents – U.S. Patent Nos. 5,514,698 ("the '698 patent) and 6,153,635 ("the '635 patent").  Both patents are identified with a "Delist Requested" flag, which first appeared in the May 2009 Orange Book Cumulative Supplement.  According to FDA's Paragraph IV Certification List, FDA received Perrigo's ANDA containing a Paragraph IV certification to the '698 and '635 patents on December 5, 2007.  This set up a potential 180-day exclusivity forfeiture under FDC Act § 505(j)(5)(D)(i)(I) for late last week, as the "later of" date was 30 months after ANDA submission.  FDA timely approved Perrigo's ANDA, however, and stated in the approval letter that:

With respect to 180-day generic drug exclusivity for Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%), Perrigo was the first ANDA applicant to submit a substantially complete ANDA for Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%), with a paragraph IV certification to the patents listed above.  Therefore, with this approval, Perrigo may be eligible for 180 days of generic drug exclusivity for Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%). . . .   The agency notes that a delisting request has been submitted for the '698 and '635 patents.  The agency is not making a formal determination at this time of Perrigo's eligibility for 180-day generic drug exclusivity.  It will do so only if another applicant becomes eligible for approval within 180 days after Perrigo begins commercial marketing of Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%). [(emphasis added)]

Now, someone could read the emphasized language above and conclude that FDA has not fully embraced the Teva decision.  After all, there has not, to our knowledge, been a counterclaim brought under FDC Act § 505(j)(5)(C)(ii)(I) that would call Perrigo's 180-day exclusivity into question.  So why even include the "punt" language in the approval letter at all?  We think that FDA included the language in the letter to cover all of the bases.  That is, as a placeholder just in case a counterclaim is brought by another applicant under FDC Act § 505(j)(5)(C)(ii)(I). 

By Diane B. McColl & Ricardo Carvajal –

It’s here!  FDA’s Center for Veterinary Medicine (“CVM”) finally implemented a "generally recognized as safe" (“GRAS”) notification program for use of ingredients in animal feed or pet food.  We have waited for this program since 1997, when it was first proposed along with FDA's Center for Food Safety and Applied Nutrition's (“CFSAN's”) GRAS notification program for human food ingredients.  CVM's efforts to establish the program were announced more than a year ago.  In the ensuing months, producers of potential new ingredients met with CVM, trying to understand how the program might work.  Now we have a basic framework.  CVM's GRAS notification program food parallels CFSAN's GRAS notification program, which has operated successfully for more than 10 years.  As CFSAN did in the early days of its program, CVM “strongly encourages” potential notifiers to discuss their plans with the Division of Animal Feeds prior to submission.

Based on CVM’s Federal Register notice and the instructions provided on its website, it appears that CVM intends to administer its program so that it is both substantively and procedurally consistent with CFSAN’s program -  with a couple of notable exceptions.  First, if the ingredient will be fed to food-producing animals, safety of the ingredient must be shown   both for target animals consuming the ingredient and for humans consuming food derived from those animals.  Thus, for both the target animal and the human populations, a GRAS notifier must establish that the proposed use of a food ingredient is not just safe, but also generally recognized as such.  Second, CVM describes its program as a “pilot” program, and notes that resources are limited in the animal food program.  Consequently, CVM does not commit to a specific time frame for responding to notifications.  While CFSAN originally set a target of 90 days for its GRAS notifications, that target has crept up to 180 days.

As with CFSAN’s program, notifiers under CVM’s program should expect their GRAS determination claims to become publicly available on the date that the GRAS notice is received.  Pivotal safety data and information (i.e., those data without which the GRAS determination cannot stand) should already be in the public domain.  Other data and information in the GRAS notice will immediately be made available to the public, subject to exemptions in FDA’s regulations implementing the Freedom of Information Act (21 C.F.R. Part 20).

By Ricardo Carvajal –

Kellogg Company has agreed to FTC’s expansion of the settlement order that the company entered into in July 2009 regarding false claims that Frosted Mini-Wheats improve children’s attention (see our prior post here).  At issue now are “dubious health claims” that Rice Krispies supports children’s immunity.

Under the modified order, Kellogg is prohibited from making any representation in connection with the marketing of any food regarding

A. the benefits, performance, or efficacy of such product for cognitive
function, cognitive processes, or cognitive health; or

B. any other health benefit of such product

unless the representation is not misleading and is adequately substantiated.  The modified order now describes FTC’s substantiation standard in detail.  Kellogg must have:

competent and reliable scientific evidence that is sufficient in quality and quantity based on standards generally accepted in the relevant scientific fields, when considered in light of the entire body of relevant and reliable scientific evidence, to substantiate that the representation is true. . .. [C]ompetent and reliable scientific evidence means tests, analyses, research, or studies that have been conducted and evaluated in an objective manner by qualified persons and are generally accepted in the profession to yield accurate and reliable results.

As we noted in a prior posting, FTC staff have repeatedly expressed concern over the use of immunity claims in promotion for foods.  However, the claim used by Kellogg (“now helps support your child’s immunity”) strikes us as relatively timid – notwithstanding the Commission’s characterization of it as a claim to “boost” immunity.  Although FTC’s action might be partially attributable to the fact that Kellogg embarked on its immunity campaign shortly after negotiating the original settlement, it appears that the Commission is prepared to challenge any questionable immunity claim – even those that don’t explicitly reference an ability to boost immunity.

By Kurt R. Karst –

Earlier this year, the U.S. Patent and Trademark Office (“PTO”) denied an application for a Patent Term Extension (“PTE”) for U.S. Patent No. 6,869,939 (“the ‘939 patent”).  The ‘939 patent is one of four patents listed in FDA’s Orange Book as covering NEXTERONE (amiodarone HCl) Injection, which FDA approved in December 2008 under New Drug Application (“NDA”) No. 22-325. 

Amiodarone has been around for a while.  It was first approved in December 1985 as CORDARONE under NDA No. 18-972.  So it was no surprise when the PTO, in March 2010, denied a PTE for the ‘939 patent based on an analysis of the “first permitted commercial marketing” criterion in the PTE statute. 

Under 35 U.S.C. § 156(a)(5)(A), the term of a patent claiming a drug shall be extended from the original expiration date of the patent if, among other things, “the permission for the commercial marketing or use of the product . . . is the first permitted commercial marketing or use of the product under the provision of law under which such regulatory review period occurred” (emphasis added).  The term “product” as used in § 156(a)(5)(A) is defined in § 156(f)(1) to mean “drug product,” which is defined in § 156(f)(2) to mean the “active ingredient of (a) new drug, antibiotic drug, or human biological product . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.”  The FDA’s PTE regulation at 21 C.F.R. § 60.3(b)(2) defines the term “active ingredient” to mean:

any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or of animals.  The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

Although the PTO had historically defined the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active moiety” (i.e., the molecule in a drug product responsible for pharmacological action, regardless of whether the active moiety is formulated as a salt, ester, or other non-covalent derivative) rather than “active ingredient” (i.e., the active ingredient physically found in the drug product, which would include any salt, ester, or other non-covalent derivative of the active ingredient physically found in the drug product), in May 2010, a 3-judge panel of the U.S. Court of Appeals for the Federal Circuit ruled in two cases – Photocure ASA v. Kappos and Ortho-McNeil Pharmaceutical, Inc. v. Lupin Pharmaceuticals, Inc. (here and here) – that the “active ingredient” interpretation of the statute is the proper interpretation.  (See our previous post here.)

The PTO’s denial of a PTE for the ‘939 patent is based on a straightforward analysis:

It is undisputed that amiodarone hydrochloride is the active ingredient of Applicant’s NEXTERONE® drug product. . . .  It is also undisputed that amiodarone hydrochloride was approved by the FDA under section 505 of the FFDCA prior to the December 24, 2008 approval of NEXTERONE®. . . .  Accordingly, the later approved NEXTERONE® (amiodarone hydrochloride) does not represent the first permitted commercial marketing or use of the “product” under the provision of law under which such regulatory review occurred.

The PTO next turns its attention to two curious statements in the PTE application – namely that NEXTERONE “is a sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride intravenous solution,” and that “[t]he sulfobutyl ether -cyclodextrin-amiodarone hydrochloride complex was not previously approved prior to the approval of NEXTERONE®.”  The PTO’s response is that these statements are irrelevant for purposes of § 156(a)(5)(A):

[A]s already stated, it is undisputed that amiodarone hydrochloride is the active ingredient of Applicant’s NEXTERONE® drug product.  The sulfobutyl ether ß-cyclodextrin component is not identified as an active ingredient of NEXTERONE® by the electronic Orange Book.  Indeed, the PTE Application itself does not identify sulfobutyl ether ß-cyclodextrin as an active ingredient of NEXTERONE®.  Accordingly, whether sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride complex has been previously approved prior to the approval of NEXTERONE® is irrelevant to the determination of whether the requirement of section 156(a)(5)(A) has been fulfilled.

The PTE applicant recently filed a Request for Reconsideration of the PTO’s denial of a PTE for the ‘939 patent “on the grounds that NEXTERONE® represents the first permitted commercial marketing or use of the Nexterone ‘product,’ sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride complex. . . .”  According to the PTE applicant:

The identification of “amiodarone hydrochloride” . . . was simply to indicate that amiodarone hydrochloride provides the pharmacological activity of the drug product.  It was the intention of Applicants to convey that the “active ingredient” in the drug product NEXTERONE® is the sulfobutyl ether ß-cyclodextrin amiodarone hydrochloride complex.

Because the definition of “active ingredient” at 21 C.F.R. § 60.3(b)(2) includes components that are “present in the drug product in a modified form intended to furnish the specified activity or effect,” and because, according to the PTE applicant, “amiodarone forms an inclusion complex with sulfobutyl ether-ß cyclodextrin,” and the  ‘939 patent “describes the interaction between amiodarone and sulfobutyl ether-ß cyclodextrin resulting in a complex in which the amiodarone is ‘part of a clathrate or inclusion complex,’”  “sulfobutyl ether-ß cyclodextrin amiodarone hydrochloride complex” is the active ingredient in NEXTERONE and the “drug product” under 35 U.S.C. § 156(f)(2).  FDA has not previously approved “sulfobutyl ether-ß cyclodextrin amiodarone hydrochloride complex,” so the approval of NEXTERONE would, according to the PTE applicant, meet the first permitted commercial marketing or use PTE criterion at 35 U.S.C. § 156(a)(5)(A).

The PTO typically holds firm to its PTE denials, so it seems unlikely that the Office will reverse the ‘939 PTE denial in light of the reconsideration request.  If that is the case here, then it is possible that more PTE litigation will be on the way.  Stay tuned!

 By Kurt R. Karst –   

Last week’s 29-page decision by the U.S. District Court for the Eastern District of Pennsylvania in In re Budeprion XL Marketing & Sales Litigation is yet more affirmation that lower courts are broadly reading and applying the U.S. Supreme Court’s 2009 decision in Wyeth v. Levine.  In Levine, the Court ruled, by a 6-3 vote, in the context of a  brand name drug, that FDA labeling approval does not preempt state laws.  Since that decision, myriad courts have taken up the issue of preemption doctrine as it applies to generic drugs (generally ruling against preemption), and the U.S. Supreme Court recently invited the Solicitor General to express the views of the United States on the topic (see our previous post here). 

In re Budeprion XL Marketing & Sales Litigation is a putative nationwide class action brought under California state consumer protection laws (i.e., California’s Unfair Competition Law and Consumer Legal Remedies Act) in which the plaintiffs allege that certain manufacturers of generic versions of the antidepressant WELLBUTRIN XL (bupropion HCl) Extended-Release Tablets failed to warn them about differences between their generic and the brand name drug, and that such differences caused undesirable effects.  According to the court, “[t]hese generics use a matrix technology rather than a membrane-release technology and rely on the size of the pill to control the release of the medication.”  As such, “[t]he generics subject to this litigation achieve peak concentrations in two hours, versus five hours for Wellbutrin XL . . . .  Plaintiffs say the more rapid release of Defendants’ drugs renders them less effective in treating depression and more dangerous than those products using a membrane-release technology.”  As we previously discussed, generic and brand name drugs can differ in release mechanism and still be therapeutic equivalents, provided the products are pharmaceutically equivalent and are demonstrated to be bioequivalent. 

In the bupropion class action, the plaintiffs contend that post-ANDA approval the generic manufacturers had a duty to disclose the differences between their products and the brand name drug by amending their labeling through FDA’s Changes Being Effected regulations.  The defendants argue in their Motion to Dismiss that “plaintiffs now directly challenge the exclusive role Congress assigned FDA to accomplish the Hatch-Waxman Act’s objectives,” and that the plaintiffs’ claims are preempted by the FDC Act and FDA’s determination that the generic WELLBUTRIN XL drug products are bioequivalent to the reference listed drug:

Recognizing the conflict between their claims and FDA’s equivalence determination, plaintiffs have tried to label their case as one about a “failure to warn.”  But this is not a personal injury case where a plaintiff seeks damages for injuries resulting from an undisclosed risk that FDA never considered or ruled on.  And none of the “failure to warn” cases concerns alleged differences between a brand and a generic product.  Here, plaintiffs’ fundamental complaint is with FDA’s decision to approve the Generic Products and allow them to remain on the market as equivalents of Wellbutrin XL.  If Plaintiffs’ allegations were right, and the Generic Products were not as safe and effective as the brand drug, then FDA could not allow the Generic Products to remain on the market as generic equivalents.  21 U.S.C. § 355(e).  Plaintiffs, however, seek to impose state-law obligations purportedly requiring defendants to disclose certain differences between the Generic Products and Wellbutrin XL, even though FDA has necessarily determined that all those differences are immaterial.  Requiring such representations would conflict directly with FDA’s determination that, as an equivalent generic, the Generic Products are “the same as a brand-name drug in: dosage, safety, strength, quality, the way it works, the way it is taken, and the way it should be used.”

And with respect to the applicability of the Levine decision, the generic drug manufacturers note that “[t]his is not a case where FDA has not ‘made an affirmative decision’ about the issue in dispute. . . .  Rather, FDA has addressed the exact issues raised by plaintiffs in finding the Generic Products to be bioequivalent to Wellbutrin XL and approving them for marketing.”  Moreover:

Were plaintiffs to prevail, FDA approval of a generic as bioequivalent would no longer be enough and generic drug manufacturers would have to engage in the very kind of safety and efficacy testing that the Hatch-Waxman Act expressly rejects for generic drug approval.  The result is undeniable: there would be fewer generic drugs developed for approval by FDA. . . .  The use of state law to second-guess FDA’s determination that the Generic Products are as safe and effective as Wellbutrin XL unquestionably would undermine Congress’s express delegation of exclusive authority to FDA to select the methods and standards for approving generic products as interchangeable with brand products, and discourage the marketing of approved products.  Such an application of state law is, thus, preempted.

The court (Judge Berle M. Schiller) was not persuaded and denied the defendants’ Motion to Dismiss.  “[T]he argument that Congress would permit state law to apply to the labeling of name brand drugs but would preempt state law actions against generic drug makers is a tough pill to swallow,” according to Judge Schiller, and “[t]he reasoning in Levine applies equally well to generic drugs.”  Central to Judge Schiller’s decision are fourt points:

• First, a generic drug manufacturer is not absolved of liability because the FDA has approved its generic product.  The Hatch-Waxman Act allows generic drug makers to expeditiously get their products to market – it does not allow generic drug makers to wash their hands of any responsibility for monitoring the safety and efficacy of their drugs once sold.

• Second, preemption is not to be lightly applied, particularly in this case because the field of law is one in which states have historically played a role.  Defendants have not pointed to any evidence of clear Congressional intent to preempt Plaintiffs’ claims, instead retracing arguments other courts have rejected. . . .   Furthermore, Plaintiffs would be left without a remedy if their state-law claim were preempted. Defendants need to posit more than the FDA’s bioequivalence determination to show that Congress meant to leave those injured by generic drug makers unable to seek redress for their injuries.

• Third, Levine leaves it beyond doubt that ultimate responsibility for the labeling of drugs remains with the maker of the drug, not the FDA.

• Fourth, although Defendants repeatedly assert that this is a case in which the FDA has already spoken and therefore a jury may not reassess the position taken by the FDA, that fact, even if correct, would not render Plaintiffs’ claims preempted. . . .  Federal laws and regulations do not leave generic drug makers impotent upon learning that their labels are inadequate or that their medication causes adverse side effects that must be reported. Generic drug makers may add or strengthen warning labels, even without prior FDA approval.

It is unclear whether the generic defendants in the case will appeal Judge Schiller’s decision.  Given the “Levine-creep” (the preemption version of “bio-creep”) that this decision represents, however, in which one has to ask what facts would, in fact, support Levine preemption, an appeal certainly seems like a possibility. 

By Ricardo Carvajal & Diane B. McColl –

The Alliance for Natural Health (“ANH”) has prevailed on summary judgment in its court challenge to FDA’s denials of, and restrictions on, certain qualified health claims regarding selenium and cancer.  The decision marks the latest chapter in a long-running battle between industry and FDA over the agency’s attempts to implement the FDC Act’s restrictions on the use of health claims in the labeling of foods, including dietary supplements. 

ANH submitted a qualified health claim ("QHC") petition to FDA which proposed numerous claims that consumption of selenium reduces the risk of some cancers.  The court’s conclusions with respect to FDA’s handling of those claims are summarized below. 

• FDA denied as “misleading on their face” claims that selenium “may reduce the risk of certain cancers” and “may produce anticarcinogenic effects.”  FDA argued that the former claim is misleading because it fails to specify the cancers on which selenium has an effect, and that the latter claim falsely implies that selenium has an effect on all cancers.  Citing the principles established in Pearson I (Pearson v. Shalala, 164 F.3d 650, 652 (D.C. Cir. 1999)), the court found FDA’s action unconstitutional in the absence of “empirical evidence that any disclaimer would fail to correct the claims’ purported misleadingness.”  If FDA cannot produce that evidence, then FDA must draft “one or more” disclaimers for those claims. 

• FDA denied a claim regarding lung/respiratory tract cancers and a claim regarding colon/digestive tract cancers on the ground that the claims were unsupported by any credible evidence.  The court conducted its own review of the underlying studies and found that FDA’s basis for discounting one or more of the studies was erroneous and not in keeping with its guidance on the evaluation of health claims.  For the lung/respiratory tract cancer claim, FDA must now draft a disclaimer that accounts for the one study deemed by the court to be supportive.  For the colon/digestive tract claim, FDA must reconsider that claim and draft a disclaimer as needed.  

• FDA entirely redrafted a claim regarding prostate cancer because the agency found the language proposed by plaintiff to be false and misleading.  The court concluded that FDA erred when it “completely eviscerated plaintiff’s claim” instead of taking the less restrictive approach of drafting one or more “short, succinct, and accurate” disclaimers.  Further, based on its review of the underlying studies, the court found FDA’s proposed claim to be contradictory and inaccurate.

Barring a successful appeal, this decision could cement in place a regime for FDA’s review of qualified health claims that is very favorable to health claim petitioners.  As a practical matter, the burden that FDA would have to meet before it can deny a qualified health claim petition would be unachievable in all but the most extreme cases – an outcome that should cheer advocates of unfettered commercial speech.

Although qualified health claims and structure/function claims are governed by different standards, this decision could raise questions with regard to whether the government’s current approach to substantiation of structure/function claims can withstand a First Amendment challenge.  FDA and FTC guidance documents maintain that there is no fixed substantiation standard for such claims; however, both agencies have suggested that a minimum of two high quality clinical studies are needed.  Query whether either agency could lawfully suppress an appropriately qualified structure/function claim that is based on a single study – or any other credible scientific evidence, for that matter.

Although individual firms should certainly profit from a less restrictive approach to the use of health and structure/function claims, there is a risk to industry writ large.  If the end result is an explosion in the use of claims based on very limited scientific support, and if those claims prove to have no merit in the long run, then consumers’ skepticism of all health-related claims can be expected to increase.  This would be an “unhappy meal” indeed.

By Susan J. Matthees –

FDA has denied a Citizen Petition requesting that FDA require drug and device companies to submit data only from non-animal test methods ("NATMs") whenever NATMs are available.  The Citizen Petition was submitted on behalf of the Mandatory Alternatives Petition Coalition (the Coalition) in 2007.  In April we reported that the Coalition had sued FDA to force the Agency to substantively respond to the Citizen Petition. 

In the denial letter, FDA explained that although the Agency shares the goal of reducing reliance on animal testing, there are currently no suitable non-animal alternatives to the testing necessary for FDA to conclude that a drug or device is safe for human use.  However, FDA stated that it intends to publish a draft guidance on the use of NATMs to “aid refinement, reduction and replacement of animal tests whenever feasible by explicitly encouraging sponsors to approach the Agency early in the development process for consultation on the suitability and acceptability of non-animal tests.”  FDA also reminded the Coalition that the Agency currently accepts a NATM where the NATM provides information that is equal to the equivalent animal testing method. 

FDA responded to each of the Coalition’s five requests in detail, mentioning several times that it “carefully considered” the particular issues.  FDA acknowledged that the Coalition is correct that animal testing models sometimes fail to predict safety risks in humans (e.g., Vioxx and HIV protease inhibitors), but explained that testing in animals is still the most reliable method for studying the safety of a drug.  FDA also stated several times that the Agency is open to recommendations for reliable NATMs and will consider any new NATMs that could provide data equal to animal testing. 

By William T. Koustas –

As we have previously reported (here, here, and here), the FTC has delayed enforcement of its Red Flags Rule (“the Rule”) several times since its original effective date of November 1, 2008.  Now, some in Congress have requested that the FTC again delay enforcement while Congress takes up legislation that would more precisely define the entities covered by the Rule.  As a result, the FTC has delayed the Rule’s enforcement until December 31, 2010, unless Congress passes legislation with an earlier effective date.   

By Ricardo Carvajal –

Senators Harkin and Hatch have introduced the Dietary Supplement Full Implementation and Enforcement Act of 2010 (S. 3414).  The statement of findings notes that FDA has been slow to implement the Dietary Supplement Health and Education Act (“DSHEA”) of 1994, and proposes a substantial increase in funding for the agency’s implementation activities – $20 million in FY 2010, $30 million in FY 2011, “and such sums as may be necessary for each of fiscal years 2012 through 2014.”  In addition, NIH’s Office of Dietary Supplements would receive $40 million in FY 2011 “for expanded research and development of consumer information on dietary supplements” (with additional sums as needed in FY2012-2014).

The additional funding would come with some strings attached.  FDA would be directed to submit an annual report to Congress on its implementation and enforcement of DSHEA that includes information on (1) funding and personnel dedicated to dietary supplement regulatory matters (including compliance with good manufacturing practice requirements); (2) FDA’s reviews of new dietary ingredient notifications, as well as enforcement actions undertaken for failure to file a notification; and (3) FDA’s requests for substantiation of claims and any follow-up actions.  FDA would also be directed to issue guidance that addresses the applicability of the definition of “new dietary ingredient” (NDI) and of the NDI notification submission requirement, among other issues.  Finally, if FDA receives an NDI notification that raises safety concerns because the supplement might contain an anabolic steroid or analogue thereof, FDA would be directed to notify DEA.  

The bill received expressions of support during a recent hearing held by the Senate Special Committee on Aging that addressed concerns about the quality and marketing of certain dietary supplements. 

By Kurt R. Karst –   

Earlier this week, we reported on the latest in the ongoing saga over a Patent Term Extension (“PTE”) for U.S. Patent No. 5,196,404 (“the ‘404 patent”) covering The Medicines Company’s (“MDCO’s”) ANGIOMAX (bivalirudin) – an order from the U.S. District Court for the Eastern District of Virginia (Alexandria Division) to the U.S. Patent and Trademark Office (“PTO”) to issue a second interim PTE for the ‘404 patent.  We also noted that outside of the current litigation, we understand that MDCO is continuing to push for passage of a bill that will legislatively extend the PTE for the ‘404 patent.  And specifically, that the latest legislative push is to get the bill attached to the Tax Extenders Act of 2009 (H.R.4213).  H.R.4213 is reportedly one of those “must pass” bills, and offers a perfect vehicle to slip in an amendment styled as an “excise tax on patent term extensions.”

Yesterday, Senator John Kerry (D-MA) introduced an amendment (SA4295) to H.R. 4213 that would grant MDCO a PTE for the ‘404 patent for the price of $65 million.  The amendment is similar to other versions of what has been dubbed the “Dog Ate My Homework Act” introduced in previous Congresses (see our previous posts here, here, and here).  The amendment would amend the PTE statute (35 U.S.C. § 156) to add new subsection (i), which states that the PTO Director:

shall accept an application under this section that was filed not later than 3 business days after the expiration of the 60-day period provided in subsection (d)(1) if the owner of record of the patent, or its agent, submits a request to the Director to proceed under this subsection not later than 5 business days after the expiration of that 60-day period.  An application accepted by the Director under this subsection shall be treated as if it had been filed within the [60-day] period specified in subsection (d)(1).

The acceptance of a PTE application pursuant to proposed 35 U.S.C. § 156(i) would be subject to a tax, which for MDCO would be “$65,000,000 with respect to any application for a [PTE], filed with the [PTO] before the date of the enactment of this section, for a drug intended for use in humans that is in the anticoagulant class of drugs” (i.e., ANGIOMAX).  Any other PTE application subject to proposed 35 U.S.C. § 156(i) would be subject to a tax equal to the sum of:

(A) any net increase in direct spending arising from the extension of the patent term (including direct spending of the United States Patent and Trademark Office and any other department or agency of the Federal Government),

(B) any net decrease in revenues arising from such patent term extension, and

(C) any indirect reduction in revenues associated with payment of the tax under this section.

The “effective date” section provides that Sen. Kerry’s amendment shall apply with respect to any PTE application made on or after the enactment of H.R.4213 or “that, on the date of the enactment of this Act, is pending, that is described in section 4491(b)(1)(A) of the Internal Revenue Code of 1986 as added by subsection (a) of this section, or as to which a decision denying the application is subject to judicial review on such date” (i.e., ANGIOMAX).  Moreover, the Kerry amendment provides that the 5-business-day period in proposed 35 U.S.C. § 156(i) “shall be deemed to begin on the date of the enactment of this Act, and, if the original term of the patent to be extended has expired, any extension or interim extension of the term of the patent granted pursuant to a request under [35 U.S.C. § 156(i)] shall be effective from the original expiration date of the patent” (once again, describing the ANGIOMAX PTE situation). 

According to Sen. Kerry’s statement made upon the introduction of the amendment “[t]he purpose of this amendment is to fix a complete anomaly in the patent law that is vital to our State.”  And according to former Surgeon General Dr. Louis Sullivan “[t]he fate of this corrective provision could be a matter of life and death for tens of thousands of patients.  The reality is that stark.  As drug innovators develop pioneering medicines, the benefits available to patients are increasing.  These medical innovators’ ability to conduct lifesaving research should not be thwarted by a confusing filing deadline.”  MDCO claims that if a PTE were applicable to the ‘404 patent, it would extend the patent expiration date until December 2014.  Without a PTE on the ‘404, generic competition is expected later this year.

By Ricardo Carvajal –

FDA has revised its draft guidance on the Reportable Food Registry (“RFR”)  to address the new electronic portal for submission of reports, and in response to recent questions that the agency received from industry.  Among the more significant changes and additions:

• A human food that contains an undeclared allergen “may be a reportable food. . . regardless of how the major food allergen was incorporated into the human food.”

• If a facility receives a bulk trailer shipment (meaning that the trailer is dropped off at the facility and the driver leaves) and the shipment is determined to contain a reportable food, the facility must submit a report even if the shipment is not off-loaded and is rejected.

• A report pertaining to a food later determined by FDA not to be a reportable food will not be entered into the RFR, but does remain in FDA’s records.

• Consumers should not use the RFR.

• The reporting obligation extends to a reportable food even if that food is manufactured solely for export.

• The reporting obligation does not extend to a reportable food in a foreign facility that exports to the U.S. and elsewhere if the reportable food is not shipped to the U.S.

In the Federal Register notice announcing the availability of the guidance, FDA asks for comments on  the meaning of “transfer” as that term is used in section 417(d)(2) of the FDC Act.  As explained by FDA:

Section 417(d)(2) of the act provides an exemption from the requirement that a responsible party submit a reportable food report. In order for the exemption to apply, the adulteration must have originated with the responsible party, the responsible party must have detected the adulteration prior to any transfer to another person of the article of food, and the responsible party must have corrected the adulteration or destroyed the food. However, Congress did not provide a definition for the term “transfer” as it is used in section 417(d)(2)(B) of the act. In Edition 1 of the guidance at Question and Answer numbers 27 and 28, and in the draft Edition 2 guidance at Question and Answer numbers E.4 and E.5, FDA said that a transfer to another person occurs when the responsible person releases the food to another person. In this document, FDA is asking for comment on whether this interpretation of the term “transfer” is appropriate, and if not, what other interpretations of the term “transfer” as it is used in section 417(d)(B)(2) of the act would be more appropriate. Specifically, we are requesting comment on whether the interpretation of the term “transfer” should be dependent upon possession of the food, whether the interpretation should be dependent on ownership of the food, or whether there are other interpretations we should consider, such as a combination of possession and/or ownership.

There have been numerous expressions of concern about FDA’s current broad interpretation of “transfer,” which severely limits the applicability of the statutory exception to the reporting requirement.  Interested parties should submit comments on this and other issues of concern by July 26, 2010 to ensure that they receive full consideration by the agency.

 By John R. Fleder & Ricardo Carvajal –

The Federal Trade Commission ("FTC") has announced a second opportunity for public comment on its proposed issuance of compulsory process orders to 48 food and beverage firms.  If those orders are issued, the FTC will demand information on marketing of food and beverages to children. The FTC is submitting its proposed information collection to the Office of Management and Budget ("OMB"), and is seeking public comment by June 24, 2010 on the proposal.  The FTC will collect data on categories of foods involved and their corresponding nutrition information, types of media techniques used, marketing expenditures, targeting by race and ethnicity, and research on psychological factors that make food advertising appealing to youth.  Among other objectives, these data will help the FTC “evaluate the impact of self-regulatory efforts on the nutritional profiles  of foods marketed to children and adolescents.” 

The FTC states that it will issue information demands to those companies whose "marketing and selling the categories of food and beverage products that appear to be advertised to children and adolescents most frequently."  Because a number of the recipients of the proposed orders are members of the Council of Better Business Bureaus Children’s Food and Beverage Advertising Initiative, the FTC believes that its current study “will account for significantly more than three-fourths of advertising expenditures directed toward children and adolescents.”  Included among the recipients are “several fruit and vegetable producers, distributors and marketers.”  The FTC estimates that each company that receives a demand for information from the FTC will be obligated to spend (on average) approximately 600 hours to comply with the FTC's demands.

Of the 48 firms that will receive the proposed orders, 40 received similar orders issued in 2007.  The FTC used the responses to those orders to prepare its 2008 report to Congress entitled Marketing Food to Children and Adolescents: A Review of Industry Expenditures, Activities, and Self-Regulation, which made a number of recommendations to food and beverage marketers.  The FTC can be expected to use the responses to the proposed orders to assess whether marketers acted on the recommendations made in the 2008 report. 

The FTC's Federal Register notice of May 25, 2010 states that potential recipients of the proposed compulsory process orders must retain potentially responsive documents and information. This position seems somewhat bizarre because it is quite unclear which companies will receive the orders.  Nevertheless, the FTC is taking the position that potential recipients of the proposed orders should retain potentially responsive information, lest they face potential criminal prosecution, according to the FTC.  Although the FTC anticipates that the collected information will become publicly available only in an anonymous or aggregated form, potential recipients should assume that responsive information could nevertheless be disclosed by the FTC (without the company's consent) in a variety of contexts, such as to Congress in response to an official request.

As we have noted in prior postings (here and here), the FTC has repeatedly indicated that it is especially concerned about food advertising directed to children.  The data collected by the FTC in response to the proposed orders can be expected to inform the agency’s decision on what types of additional actions are appropriate to address this issue.

The deadline for submission of comments is June 24, 2010. 

By Kurt R. Karst –   

In a somewhat unusual move, the U.S. Supreme Court has asked the U.S. Department of Justice (Solicitor General of the United States) to weigh in on generic drug preemption.  The move signals that the Court has continued interest in this issue, and comes in the context of two Petitions for Writ of Certiorari in which various generic drug manufacturers have appealed the U.S. Court of Appeals for the Eighth Circuit’s November 27, 2009 decision in Mensing v. Wyeth, Inc.

As we previously reported, Mensing addressed, among other things, whether the FDC Act preempts failure to warn claims against generic drug manufacturers – specifically, generic REGLAN (metoclopramide).  In reversing an October 2008 decision from the U.S. District Court for the District of Minnesota in which the court dismissed certain failure to warn claims against generic manufacturers on the basis of federal preemption, the Eighth Circuit, relying on the Supreme Court’s 2009 decision in Wyeth v. Levine, rejected arguments that failure to warn claims against generic manufacturers are preempted by the FDC Act (and the Hatch-Waxman Amendments in particular) because they create an impermissible conflict with federal law. 

The two Petitions for Writ of Certiorari (here and here) were filed in February 2010 and present almost identical questions for the Supreme Court’s consideration:

Whether the Eighth Circuit abrogated the Hatch-Waxman Amendments by allowing state tort liability for failure to warn in direct contravention of the Act’s requirement that a generic drug’s labeling be the same as the FDA-approved labeling for the listed (or branded) drug.

The first Petition is docketed as Docket No. 09-993 and was filed by PLIVA, Inc., Teva Pharmaceuticals USA, Inc., and UDL Laboratories, Inc.  The second Petition is docketed as Docket No. 09-1039 and was filed by Actavis Elizabeth, LLC.  Opposition and reply briefs have been submitted in both cases (as well as an amicus brief from GPhA) and are available on SCOTUSBlog here (scroll down to the bottom of the page). 

Shortly after the Eighth Circuit issued its decision in Mensing, the U.S. Court of Appeals for the Fifth Circuit came to a similar conclusion in Demahy v. Actavis.  That decision has not (yet) been appealed to the Supreme Court.  (For a nice overview of the current generic drug preemption landscape, see the Washington Legal Foundation’s recent Legal Backgrounder on the topic.)

By Ricardo Carvajal –

FDA announced that Reportable Food Registry ("RFR") reports can now be submitted through the new FDA-NIH Safety Reporting Portal, which will also accept reports about problems with pet food, animal drug adverse event reports, and human gene transfer clinical trial adverse event reports.  Of particular significance to those submitting RFR reports, the new portal will allow submitters to save drafts – a feature that was sorely missing from the RFR electronic portal.