By Karla L. Palmer and Peter M. Jaensch

On November 24, 2010, using its emergency authority under section 202 of the Controlled Substances Act (“CSA”) (21 U.S.C. § 812), the U.S. Drug Enforcement Administration (“DEA”) published a Notice of Intent to temporarily place five synthetic cannabinoids in Schedule I of the CSA.  75 Fed. Reg. 71635 (Nov. 24, 2010). The five chemicals, JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol, are used to make “fake pot” products.  These “smokable herbal blends” have been marketed as being legal substances, and have been increasing in popularity among teenagers and young adults because they produce a high similar to that produced by marijuana (also a Schedule I substance).

The DEA announced in its related press release that the products consist of “plant material that has been coated with research chemicals that mimic THC, the active ingredient in marijuana.”  Brands that the DEA specifically referenced include “Spice, “K2”, “Blaze” and “Red X Dawn,” and are typically labeled as “incense” in order to disguise their actual and intended purpose.  Although the products typically are marketed with disclaimers that they are not intended for human consumption, retailers promote the fact that a routine urinanalysis will not detect their presence, and they specifically market the products to young adults and teens.  See 75 Fed. Reg. at 71637.  The FDA has not approved these chemicals for human consumption, and the products are not safe for use under medical supervision.  Nor is there any oversight concerning their manufacturing process.  The DEA’s call for emergency scheduling was driven in part by the increase in incident reports from poison control centers, hospitals and various law enforcement agencies concerning the abuse of these synthetic cannabinoids.

Under its emergency authority, to which the DEA may turn as necessary to avoid an imminent hazard to the public safety, these substances will remain in Schedule I  for one year, with the possibility of a 6-month extension.  During the temporary scheduling period, the DEA and the Department of Health and Human Services will study the propriety of a permanent controlled substance status.  In order to temporarily schedule the substances using its emergency authority,  the DEA was required to consider three of the eight factors in 21 U.S.C. § 811(c).  The DEA set forth its findings with respect to the following factors 4, 5, and 6: (4) history and current pattern of abuse (finding that the increasing popularity of these products has led to both long term and acute public health and safety problems); (5) the scope, duration and significance of abuse (since appearing in the United States in 2008, there have been over 1500 reported health-related communications related to the use of these spiked products; and (6), what, if any risk to the public health exists (finding for several detailed reasons that the products pose an imminent threat to public health and safety).

Schedule I controlled substances are those substances that, in addition to having a high potential for abuse, have no recognized medical use. The five chemicals will be subject to the “regulatory controls, and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, possession, importing and exporting of a Schedule I controlled substance under the CSA.”  75 Fed. Reg. 71637. As of October 15, 2010, 15 states and European and Scandinavian countries have taken measures to control these synthetic products.

By John A. Gilbert & Karla L. Palmer –

The Drug Enforcement Administration (“DEA”) recently published a decision that considers the scope of a pharmacist’s “corresponding responsibility” under 21 C.F.R. § 1306.04(a).  East Main Street Pharmacy (Affirmance of Suspension Order) (Docket No. 09-48) (75 Fed. Reg. 66149 (Oct. 27, 2010)) (“EMS”).  As background, 21 C.F.R. § 1306.04 provides that while “the responsibility for the proper prescribing and dispensing of controlled substances is upon the prescribing practitioner . . . a corresponding responsibility rests with the pharmacist who fills the prescription.”  21 C.F.R. §1306.04.  The regulation further states, “the person knowingly filling such a purported prescription, as well as the person issuing it [is] subject to the penalties provided for violations of the provisions of law relating to controlled substances.” Id.  Thus, a pharmacist is prohibited from filling a prescription for controlled substances “when he either knows of or has reason to know that the prescription was not written for a legitimate purpose.” 75 Fed. Reg. at 66163.  Further, when prescriptions are not issued for a legitimate medical purpose, a “pharmacist may not intentionally close his eyes and thereby avoid [actual] knowledge of the real purpose of the prescription.”  Id. (Quotations and citations omitted) (emphasis added).

Pharmacists are well trained and aware of their “corresponding responsibility.” They must only fill valid prescriptions for controlled substances issued by a legitimate practitioner for a legitimate medical purpose.  Nevertheless, the standard for what exactly is – and, specifically, what exactly is the extent of — a pharmacist’s “corresponding responsibility” has been a troublesome concept for practitioners and pharmacies alike.  Admittedly, the pharmacist in the EMS matter allegedly engaged in egregious dispensing and recordkeeping misconduct, and the case involved one bad doctor (who the Deputy Administrator called a “drug dealer”).  And, although this may be a case where over-the-top facts indeed make bad law, both pharmacists and practitioners should be mindful of the EMS opinion because the DEA has taken significant strides to clarify the scope of a pharmacist’s corresponding responsibility. 

First, faced with respondent’s assertion that the “corresponding responsibility” standard is vague, “unknown” and “ambiguous,” the DEA stated that the standard is constitutional: Federal courts have had “little problem” applying the DEA regulation, which gives “fair notice that certain conduct is proscribed.”  Id. at 66163. 

The DEA next addressed certain “red flags” that should have given the respondent pharmacist a “reason to know” that the prescriptions patients presented to him were not legitimate.  Importantly, the DEA did not focus on whether the pharmacist had “actual knowledge” that the prescriptions were not issued for a legitimate medical purpose, but instead whether the pharmacist had “reason to know [they] were not issued for a legitimate medical purpose by a practitioner acting in the usual course of professional practice.” Id.

In reviewing the pharmacist’s conduct (and citing the government’s unrefuted expert), the DEA stated that the pharmacist ignored several signs that the prescriptions written by the physician were not legitimate.  These flags include the following: (1) “ample evidence” showing that the respondent repeatedly dispensed “cocktailed” prescriptions for oxycodone, hydrocodone, alprazolam, and carisoprodol; finding that this combination prescription is “well known in the pharmacy profession as being used by patients abusing prescription drugs;” (2) no individualization of dosing by the prescribing physician; (3) filling multiple prescriptions for the strongest formulations of hydrocodone and alprazolam; (4) requests for early dispensing of refills; (5) refilling prescriptions of patients or doctors located hundreds of miles away from the pharmacy; (6) an overwhelming proportion (95%) of prescriptions filled by the pharmacy were controlled substances prescriptions; (7) the pharmacist did not reach out to or otherwise contact other pharmacists to determine why they were not filling a particular doctor’s prescriptions; (8) filling prescriptions of patients that travelled to the pharmacist in groups; (9) filling a larger percentage of cash prescriptions. (“This too, was a red flag as ‘[a]ny reasonable pharmacist knows that a patient that wants to pay cash for a large quantity of controlled substances is immediately suspect.’”); and (10) “verification” of a prescription as “legitimate” was not satisfied simply because the practitioner performed MRI’s and blood tests on the patients.  Id. 

Presented with the above evidence, the DEA stated that even if the pharmacist had verified with the physician “each and every” prescription, the evidence showed he still violated his corresponding responsibility because many of the prescriptions “patently served no legitimate medical purpose.” Id. 

The DEA also stated that the single fact that the pharmacist dispensed high quantities of commonly abused drug cocktails containing oxycodone, hydrocodone, and alprazolam and carisoprodol should have called into question the legitimacy of the prescriptions.  Id. at 66164-65.  The DEA added that “the other evidence,” including all of the evidence referenced above, was “simply icing on the cake” that the pharmacist violated his corresponding responsibility to fill only legitimate prescriptions issued for a legitimate medical purpose.  Id. at 66165.  When respondent presented some evidence concerning his refusal to fill prescriptions from pain clinics after he received notice to stop filling from the Ohio Board of Pharmacy, the DEA responded that a “responsible DEA registrant should be able to make these determinations without the authorities having to provide him the information on a silver platter.” 

Pain experts would certainly argue that in many cases DEA's red flags are in fact the basis for legitimate pain treatment, e.g., the “pain cocktail” is often prescribed because of the anxiety and muscle tension experienced by pain patients.  However,  pharmacists must be attentive to these factors, “red flags,” or signs — as part of their corresponding responsibility to fill only prescriptions that are issued for a legitimate medical purpose.

By Ricardo Carvajal - 

FDA announced that its Food Advisory Committee will meet on March 30 and 31, 2011, “to discuss whether available relevant data demonstrate a link between children’s consumption of synthetic color additives in food and adverse effects on behavior.”  Earlier this year, the European Union ("EU") moved to require the use of a health warning on food (including beverages) containing certain colors after the publication of a study that suggested a possible association between those colors and hyperactive behavior in children.  In the EU, the label of a food that contains one or more of the affected colors and that is produced after July 20, 2010, must state: "may have effects on activity and attention in children."  Among the colors subject to the EU warning requirement are FD&C Yellow 5, FD&C Yellow 6 and FD&C Red 40.

By Jeffrey K. Shapiro & Carmelina G. Allis –

FDA’s review of 510(k) program continues to cause concern in Congress. 

On November 24, 2010, the Minnesota delegation, including unlikely collaborators Senator Al Franken and Representative Michele Bachmann, sent a letter to Dr. Hamburg asking “FDA to review the impact of its recommendations [to the 510(k) program] on patient access as well as [Minnesota’s] economy.” 

They stated:  “As members of the Minnesota delegation, we want to work with the FDA toward a larger goal of saving and improving patients’ lives. . . Changes that may jeopardize that goal should not be made unless there is clear evidence that the changes are necessary to address a demonstrated public health problem.” 

The Minnesota lawmakers made clear that FDA should ensure that changes to the 510(k) program not stifle innovation or delay patient access to new treatments.

We previously reported on FDA’s August 2010 report recommending changes to the 510(k) program.  Our earlier post briefly discussed the proposed changes, and raised concerns with some of the agency’s recommendations because of their potential negative effect on the medical device industry and the 510(k) program. 

We also previously reported on an October 12, 2010, letter sent by House lawmakers to FDA’s Commissioner Dr. Hamburg asking to delay the implementation of certain changes that the agency is considering for the 510(k) program.  In the letter, the lawmakers raised concerns with the agency’s recommendations regarding rescission authority, split and multiple predicates, intended use and indications for use, mandatory pre-market inspections and clinical data for a subset of Class II devices, and proprietary information.

By Ricardo Carvajal –

By a vote of 73 to 25 (see the roll call here), the Senate has passed S. 510, the Food Safety Modernization Act.  As we noted in a prior posting, the Senate HELP Committee released a compromise agreement in August that would impose numerous new requirements on industry, and bestow numerous new authorities on FDA.  The version of the legislation passed by the Senate retains the major elements of the compromise agreement.  Given that the House of Representatives passed a similar bill last year, the stage is now set for a vote on, and possible enactment of, the Senate bill (perhaps within the next week).

Thanks to our faithful readers, we made the list for the annual American Bar Association (“ABA”) Journal Blawg 100 for the second year in a row.  The editors of the ABA Journal announced the top 100 best law blogs by lawyers, for lawyers earlier this week.  The top 100 blogs are organized in 12 categories (we’re in the “Torts” category).  Readers can now vote for their favorite blogs from among the top 100 in each of the 12 categories.  Voting ends at close of business on December 30th.  Winners will be announced in January. 

One again, we thank our readers.  We are honored by the recognition we have received.  

By Kurt R. Karst –      

Recent judicial setbacks for the Federal Trade Commission (“FTC’) in actions challenging patent settlement agreements (or what opponents call “pay-for-delay” or “reverse payment” agreements) and opposition from both Republicans and Democrats to the inclusion of the Preserve Access to Affordable Generics Act (S. 369) in the Fiscal Year 2011 Financial Services and General Government Appropriations Bill (S. 3677) may cause the FTC to consider “Plan C” to address such agreements, according to Commissioner J. Thomas Rosch.

During the World Generic Medicine Congress Americas 2010 earlier this month, Commissioner Rosch remarked that the FTC is mulling issuing its own rules next year that would shift the burden of proof to require companies to prove that patent settlement agreements are not anti-competitive.  In late July, the U.S. Senate Committee on Appropriations approved the inclusion of the Preserve Access to Affordable Generics Act in the report (Senate Report No. 111-238) accompanying S. 3677.  The legislation would make patent settlement agreements presumptively anticompetitive and unlawful if challenged by the FTC, unless it can be demonstrated “by clear and convincing evidence that the procompetitive benefits of the agreement outweigh the anticompetitive effects of the agreement.”  The patent settlement provisions were added to the report accompanying S. 3677 after the Senate decided to drop the House patent settlement agreement provisions passed as part of a package of amendments to the War Funding Bill (H.R. 4899) – see our previous post here.

In September and October, some Republicans and Democrats sent separate letters (here and here) to their respective party leaders requesting that the provisions of S. 369 not be included in any appropriations bill this Congress.  The letters also note substantive concerns with the provisions of S. 369.  For example, the Republican letter alleges that S. 369 gives “excessive power over such settlements to the FTC – a power that the FTC has shown itself in the past to be unable to exercise in a responsible or economically rational manner – and that the bill would do serious violence to the Hatch-Waxman process for the market entry of generic drugs.”  It is unclear how an FTC “Plan C” to address patent settlement agreements would address such concerns. 

During his speech, titled “The Antitrust/Intellectual Property Interface: Thoughts on How To Best Wade Through the Thicket in the Pharmaceutical Context,” which primarily focused on patent settlement agreements, but also touched on myriad other issues, including patent use codes, authorized generics, citizen petitions, and so-called “product hopping,” Commissioner Rosch commented that although he supports a legislative fix to address patent settlement agreements – and specifically pending legislation (with the possible exception of the “clear and convincing” standard) – he thinks any legislation should stand or fall on its own merits.  According to Commissioner Rosch:

. . . . I believe a legislative fix is likely the only way to eliminate these anticompetitive settlements.  Nevertheless, where I depart from the Chairman and perhaps the rest of the Commission (although I can’t say for sure) is on process. In my view, the legislation should rise or fall on its own merit; put differently, I think tacking it on to the war funding bill is a terrible idea.  If the goal is to put money back in consumers’ pockets, then that is what we should be doing – not funding the war.

Commissioner Rosch also waded into the FTC’s challenge concerning a patent settlement agreement on generic ANDROGEL (testosterone gel) 1% (i.e., In re: AndroGel Antitrust Litigation), commenting that the case “should be winnable, not withstanding the popularly-held view that the FTC’s chances are slim . . . .” 

As we previously reported, this case stems from a February 2009 challenge by the FTC and the California Attorney General concerning Solvay’s ANDROGEL in which the FTC alleged that Solvay and generic companies violated various federal antitrust laws when they agreed to dismiss patent infringement litigation in exchange for a profit-sharing arrangement and provided the generic competitors would not launch their generic versions of ANDROGEL until 2015.  In February 2010, in a setback to the FTC, the U.S. District Court for the Northern District of Georgia (Atlanta Division) largely dismissed the case.  In June, the FTC filed a notice of appeal to the U.S. Court of Appeals for the Eleventh Circuit.  As  reported by our fellow bloggers over at PatentDocs, the defendants-appellees in the case recently filed a brief arguing that the district court’s judgment should be affirmed.

By Susan J. Matthees –

Congresswoman Louise Slaughter (D-NY) recently sent a letter to FDA Commissioner Margaret Hamburg requesting that FDA ban the use of triclosan in consumer products.  Triclosan is commonly used as an antibacterial agent in topical antiseptic products, such as soaps and hand sanitizers, and is also found in some toothpastes, mouthwashes, and similar consumer health products.  The ingredient is included in FDA’s ongoing review of over-the-counter (OTC) healthcare antiseptic and first aid antiseptic drug products, but the use of triclosan in toothpaste was approved via an NDA.  Although FDA states that “[t]riclosan is not currently known to be hazardous,” some recent studies have suggested that triclosan may be an endocrine disrupter and may contribute to antibiotic resistance.  Congresswoman Slaughter’s letter points to those recent studies as a cause for concern and justification for a ban on the use of triclosan in consumer products.  In particular, the letter states that that antibiotic resistance and contaminated water, due in part to the use of triclosan, “have created a public health crisis in the United States.”  The letter also points to studies that suggest that triclosan may harm the environment and human health as reason for the ban. 

Slaughter’s letter comes just months after the Natural Resources Defense Council (“NRDC”) filed a Complaint in the U.S. District Court for the Southern District of New York against FDA to try to force the Agency to finalize its topical antimicrobial drug products monograph.  We posted on the suit in August.  The NRDC subsequently filed a Motion for Summary Judgment asking the court to declare unreasonable FDA’s delay in finalizing the Agency's topical antimicrobial drug products monograph and to order FDA to finalize the monograph within ninety days.  FDA is in the process of reviewing the safety of triclosan and intends to make those findings public in spring 2011.

By Ricardo Carvajal –

It’s the time of year for holiday food safety alerts.  The home kitchen has long been recognized as a significant source of foodborne illness.  Reliable data are hard to come by, but a recent survey and study suggest that consumer awareness and implementation of basic food safety measures continues to lag. 

It’s not clear what proportion of the public health toll exacted by foodborne illness is attributable to consumer mishandling – or, for that matter, what that toll is.  Although the statistics of 5,000 deaths and 325,000 hospitalizations are widely cited in the press, in blogs maintained by personal injury lawyers,  in government reports, and even in food safety legislation pending in Congress, some have openly questioned the accuracy of those statistics.  The need for updated statistics has been recognized by FDA, which has held public workshops on the subject of how to measure progress in food safety, and updated estimates from CDC are said to be on the way.  In the meantime, don’t pass up your chance to display your food safety savvy.

By Ricardo Carvajal & Diane B. McColl –

FDA issued warning letters to the manufacturers of certain caffeinated alcoholic malt beverages contending that the products are adulterated under the Federal Food, Drug, and Cosmetic Act (“FDC Act”) because caffeine is not an approved food additive for its use in those beverages.  For its part, FTC issued warning letters to the same manufacturers contending that the marketing and sale of the beverages might constitute an unfair or deceptive act or practice in violation of the Federal Trade Commission Act (“FTC Act”).  The letters describe scientific and anecdotal evidence of harm associated with the beverages, request prompt corrective action, and give the manufacturers 15 days to respond.

Because alcoholic beverages are food, the use of substances such as caffeine in those beverages is potentially subject to premarket approval under the food additive provisions of the FDC Act unless that use is generally recognized as safe (“GRAS”) or the subject of a prior sanction by the agency.  As we noted in a prior blog posting, FDA questioned the regulatory status of the beverages a year ago, and asked manufacturers to provide information demonstrating that the use of caffeine in their beverages is GRAS.  One beverage manufacturer submitted a comprehensive response in the form of a GRAS notice providing FDA with a summary of the basis upon which the manufacturer concluded that the use of caffeine as a flavoring ingredient in alcoholic beverages at levels of up to 200 parts per million is GRAS.  The manufacturer's conclusion was based upon the consensus opinion of a panel of independent scientific experts that such use is GRAS based on scientific procedures.  The safety evaluation described in the GRAS notice focuses primarily on traditional toxicological parameters (e.g., absorption, distribution, metabolism, and excretion; acute and chronic toxicity; and carcinogenicity, genotoxicity, and teratogenic effects).  Described as “not related specifically to the safety-in-use of caffeine in alcoholic beverages," the scientific evidence relating to behavioral effects of caffeine and alcohol combined are also briefly discussed in the GRAS notice.  

FDA’s warning letter makes clear that the agency finds the pending GRAS notice wanting.  FDA faults the manufacturer (and presumably the expert panel)  for relying “primarily upon safety studies of caffeine alone (i.e., not in the presence of alcohol),” and for not giving greater consideration to “studies that have reported the adverse behavioral effects elicited by the co-consumption of caffeine and alcohol.”  However, neither the FDC Act nor its implementing regulations make clear that the safety evaluation of a substance added to food should include consideration of potential “adverse behavioral outcomes.”  Nor is it readily apparent that, in considering whether the use of an ingredient in food is safe, one must consider the potential behavioral impact of  packaging and marketing of the finished food.  Yet these factors are at the crux of FDA’s conclusion that the use of caffeine in the alcoholic beverages that are intended for adults (> 21 years of age in most states) targeted by the warning letters is not GRAS:

GRAS status is not an inherent property of a substance, but must be assessed in the context of the intended conditions of use of the substance (section 201(s) of the Act [21 U.S.C. § 321(s)]). The assessment includes a consideration of the population that will consume the substance (21 CFR 170.30(b); section 409(b) of the Act [21 U.S.C. § 348(b)]). Therefore, the scientific data and information that support a GRAS determination must consider the conditions under which the substance is safe for the use for which it is marketed. Reports in the scientific literature have raised concerns regarding the formulation and packaging of pre-mixed products containing added caffeine and alcohol. For example, these products, presented as fruity soft drinks in colorful single-serving packages, seemingly target the young adult user. Furthermore, the marketing of the caffeinated versions of this class of alcoholic beverage appears to be specifically directed to young adults (Bonnie and O'Connell, 2004). FDA is concerned that the young adults to whom these pre-mixed, added caffeine and alcohol products are marketed are especially vulnerable to the adverse behavioral effects associated with consuming caffeine added to alcohol, a concern reflected in the publicly available literature (O'Brien et al., 2008; Simon and Mosher, 2007).

To be sure, the potential health risks associated with caffeinated alcoholic beverages posed a thorny challenge for FDA.  But in seeking to address those risks, it appears that FDA has broadened the scope of factors that must be considered in evaluating the safety of substances added to food – and thereby introduced an element of uncertainty into the conduct of those evaluations when "behavioral effects” might be at play.

As for the warning letters sent out by FTC, those make clear that the two agencies have been collaborating closely on the matter.  FTC’s view that the marketing and sale of the beverages might constitute an unfair or deceptive act or practice in violation of the FTC Act is premised in part on FDA’s finding of adulteration:

The FDA’s warning that caffeine is an “unsafe food additive,” as used in Four Loko, is a relevant consideration in the FTC’s analysis of whether the marketing of caffeinated alcohol products such as Four Loko and Four Maxed is deceptive or unfair under the Federal Trade Commission Act.  In the past, the FTC has accorded significant weight to FDA findings regarding product safety and efficacy.

Significant as FDA and FTC’s actions may be, they are only part of the challenge faced by manufacturers of caffeinated alcoholic beverages.  A number of states are acting to prohibit the sale of those beverages, and if history is any guide, product liability actions cannot be far behind.

By Kurt R. Karst –      

Sandoz Inc.’s recent Complaint filed in the U.S. District Court for the District of Columbia concerning Orange Book-listed U.S. Patent No. 7,429,602 (“the ‘602 patent”) covering ELESTAT (epinastine HCl) Ophthalmic Solution, could, if successful, serve as a model for future cases involving patent delistings. 

FDA approved ELESTAT under NDA No. 21-565 on October 16, 2003 with a period of 5-year New Chemical Entity (“NCE”) exclusivity that, according to the 2008 Orange Book, expired on October 15, 2008.  (Presumably this date is incorrect and the NCE exclusivity expiration date was, in fact, October 16, 2008.)   No patents were listed in the Orange Book for ELESTAT until Friday, October 10, 2008, when the ‘602 patent, which was issued on September 30, 2008, was received by FDA.  (The electronic Orange Book was first updated on October 14th to reflect the addition of the ‘602 patent.)  Thus, prior to the ‘602 patent listing, no ANDA could have been submitted to FDA for a generic version of ELESTAT until the expiration of NCE exclusivity on October 16th.  With the ‘602 patent listing, however, the law permitted the submission of an ANDA beginning at year 4 of the 5-year NCE exclusivity period. 

Some ANDA sponsor was on its game, as FDA’s Paragraph IV Certification List shows that the first ANDA containing a Paragraph IV certification to the ‘602 patent was submitted to FDA on October 14, 2008.  (An ANDA containing a Paragraph IV certification to the ‘602 patent could have been submitted as early as October 10th when the patent was officially considered to be Orange Book-listed.  An after-hours submission on October 10th would not have been considered submitted to FDA until the next business day, Tuesday, October 14th, as Monday, October 13th was a federal holiday – Columbus Day.)  This certification qualified the ANDA sponsor as a “first applicant” eligible for 180-day exclusivity.

According to Sandoz’s October 19, 2010 Complaint, the company submitted ANDA No. 90-950 to FDA on October 15, 2008 without a Paragraph IV certification.  On October 17th, Sandoz reportedly amended ANDA No. 90-950 to contain a Paragraph IV certification to the ‘602 patent.  As such, Sandoz is a subsequent applicant subject to a first applicant’s 180-day exclusivity, unless that exclusivity is forfeited under one of the various forfeiture provisions established by the 2003 Medicare Modernization Act (“MMA”). 

After FDA received ANDA No. 90-950, Sandoz provided notice of its Paragraph IV certification to the NDA holder and patent owner, but was not sued for patent infringement.  In July 2009, Sandoz filed a declaratory judgment action (Case No. 1:09-cv-01444) in the U.S. District Court for the District of Columbia seeking a declaration from the court that the ‘602 patent is invalid, unenforceable, or would not be infringed by Sandoz’s proposed generic version of ELESTAT.  That case was voluntarily dismissed by Sandoz on October 5, 2009 after a statutory disclaimer with respect to the ‘602 patent was filed with the U.S. Patent and Trademark Office and a request sent to FDA to delist the ‘602 patent from the Orange Book. 

At the time a patent delist flag was added to the Orange Book for the ‘602 patent, FDA’s position with respect to 180-day exclusivity forfeiture under the failure-to-market provisions was that the mere request to delist a patent from the Orange Book was an event that could lead to a forfeiture.  That all changed earlier this year, however, with the D.C. Circuit’s March 2, 2010 decision in Teva Pharms USA, Inc. v. Sebelius.  In that case, a 3-judge panel of the D.C. Circuit ruled in a 2-1 decision concerning 180-day exclusivity for generic COZAAR (losartan potassium) Tablets and HYZAAR (hydrochlorothiazide; losartan potassium) Tablets that a mere patent delisting request is not enough to trigger a forfeiture event under the failure-to-market forfeiture provision at FDC Act § 505(j)(5)(D)(i)(I), and that there is “no reason to conclude that the 2003 addition of forfeiture provisions meant to give the brand manufacturer a right to unilaterally vitiate a generic’s exclusivity.”  (As we previously reported, the U.S. Supreme Court has been petitioned to review the ruling in Teva Pharms USA, Inc. v. Sebelius.)

Given the changed landscape created by the D.C. Circuit in the losartan case, the disclaimer of the ‘602 patent and the subsequent request that FDA delist the patent from the Orange Book that presumably led Sandoz to voluntarily dismiss the company’s July 2009 declaratory judgment action could no longer serve as an event to trigger 180-day exclusivity forfeiture in April 2011 (i.e., the “later of” date of the two bookend events described at FDC Act § 505(j)(5)(D)(i)(I)).  Instead, 180-day exclusivity remains intact . . . . absent a forfeiture event.  And that is exactly what Sandoz’s October 2010 Complaint seek to create.

Sandoz’s October 2010 Complaint requests a declaratory judgment that the ‘602 patent is invalid and unenforceable, and that Sandoz’s proposed generic ELESTAT drug product does not infringe the ‘602 patent.  But can an applicant seek a declaratory judgment against a disclaimed patent?  What is the actual and justiciable controversy?  Citing the recent Federal Circuit decision in Teva Pharms. USA, Inc. v. Eisai Co. Ltd., Case No. 2009-1593 (Fed. Cir. Oct. 6, 2010), in which the Court ruled that a subsequent Paragraph IV filer has a legally cognizable interest in when a first-filer’s 180-day exclusivity period begins for declaratory judgment purposes, Sandoz states in its Complaint that an actual and justiciable controversy exists regarding validity and infringement of the ‘602 patent “[b]ased on Sandoz’s intent to launch its generic 0.05% Epinastine Ophthalmic Solutions as soon as legally permissible, and the fact that the FDA will not approve Sandoz’s ANDA until the 180-day exclusivity period has run or been forfeited. . . .”  Stay tuned. . . .  this could get even more interesting!

By Kurt R. Karst –      

Last month FDA responded to an August 25, 2010 request from New Jersey State Senator Joseph F. Vitale (D) concerning pending legislation – Assembly Bill 1995 (the State Senate version of which is Senate Bill 961) – that, if enacted, would require pharmacists to dispense epilepsy drugs from the same manufacturer as previously dispensed for certain patients, unless otherwise prescribed.  Although FDA’s response does not provide the Agency’s position on Assembly Bill 1995 as Sen. Vitale requested, it does provide some insight into FDA’s current thinking on the substitution of bioequivalent generic anti-epileptic drugs for their brand-name counterparts. 

The issue of generic anti-epileptic drug substitution has been brewing for a few years.  Questions have been raised about whether there is an increased risk of so-called “breakthrough” seizures or toxic side effects when patients are switched from a brand name anti-epileptic to a generic version.  Still pending at FDA is a 2006 citizen petition requesting that the Agency address the issue of brand-name and generic anti-epileptic drug substitution. 

In its response to Sen. Vitale, FDA comments that “[t]o date, we have not seen any scientific evidence that demonstrates a problem with therapeutic equivalence for this group of products or any other class of generic drug products.  Those who are questioning the quality of generic epilepsy products have produced only anecdotal evidence.”  Nevertheless, FDA further states:

[W]e believe that the concerns of some of those raising questions (in particular, physician groups) can not be dismissed lightly.  Because of FDA’s respect for these groups and the concern that patients may lose confidence in their prescribed medications, we have sought to conduct further study.  Our decision to further study this issue does not stem from doubt within the agency about data we currently have on approved generic epilepsy products.  Rather, it is based on a desire to obtain further independent scientific evidence that might address these concerns.

As we previously reported, last year Congress requested in the Conference Report (Report No. 111-279) accompanying the 2010 Agriculture, Rural Development, FDA, and Related Agencies Appropriations Act (Public Law No. 111-80) that FDA examine and report on “A” rated anti-epileptic drugs (i.e., drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products).  According to the Conference Report:

The conferees request the FDA report on adverse events and seizures associated with brand and generic anti-epileptic drugs.  Specifically, the agency should examine the pharmacokinetic profiles of “A” rated anti-epileptic drugs from different manufacturers of the same therapeutic agent.  The Committee directs the FDA to submit a report not later than September 30, 2010, detailing whether the agency believes that any changes to the current bioequivalence testing should be recommended.

Your intrepid bloggers understand that FDA did not submit the report by the September 30, 2010 deadline and that the Agency is still working on the report.  It is unclear when the report might be completed and submitted to Congress.  Nevertheless, FDA’s response to Sen. Vitale seems to give some foreshadowing as to what conclusions the Agency may include in its report.

By Ricardo Carvajal –

An article in the current edition of the Food and Drug Law Institute’s Update discusses a recent development in the European Union's regulation on health claims used in food labeling that could have the effect of suppressing publication of scientific research on the health benefits of food substances. Given that scientific research and collaboration is an international phenomenon, the negative effect of the European Commission's current direction might well be felt in the United States.

On December 9, 2010, Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst will speak at a webinar on accelerated drug and biologic approvals. 

In 1992, FDA published final regulations providing for the “accelerated approval” of applications for certain new drugs and biologics. Section 506 of the FDC Act, created in 1997, codified and expanded on FDA’s Accelerated Approval regulations. Both provisions include requirements for sponsors to conduct post-approval studies. Fast track and “accelerated approval” are conditioned on a sponsor’s commitment to timely complete required postmarketing studies to demonstrate the product’s clinical benefits. FDA may expedite the withdrawal of approval of an application if a sponsor fails to perform the required postmarketing study with due diligence, or if a postmarketing clinical study fails to verify clinical benefit.  FDA has approved scores of products under both the fast track and accelerated approval procedures, but has never withdrawn approval for a sponsor’s failure to conduct post-approval studies.  Only recently has FDA threatened to do so.

The December 9th webinar is titled “Navigating The FDA Accelerated Approval Process” and will be moderated by Pharmalot’s Ed Silverman.  Additional information on the webinar, including how to register, is available here.

By William T. Koustas –

The confirmation hearing for Michele M. Leonhart for the Administrator of the U.S. Drug Enforcement Administration (“DEA”) was held by the Senate Judiciary Committee on Wednesday, November 17, 2010.  Ms. Leonhart has been Acting DEA Administrator since the resignation of former DEA Administrator Karen Tandy in the fall of  2007.  Ms. Leonhart was previously (unanimously) confirmed as Deputy DEA Administrator back in 2004 during the administration of President George W. Bush.  President Obama nominated Ms. Leonhart for the position of  DEA Administrator in February 2010.

The relatively non-controversial hearing lasted approximately three hours.  Ms. Leonhart was introduced at the hearing by Senators Diane Feinstein (D-Cal.), Amy Klobuchar (D-Minn.) and Al Franken (D-Minn.), all of whom endorsed her nomination.

Ms. Leonhart received questions from various senators including Senators Herb Kohl (D-Wis.), Sheldon Whitehouse (D-RI), Jeff Sessions (R-Ala.) and Chairman Patrick Leahy (D-VT).  In response to a question from Chairman Leahy regarding the issue of abuse of prescription drugs, Ms. Leonhart acknowledged that it is a growing problem, particularly among teenagers, and insisted that the answer was a combination of better education and enforcement, including enforcement against organized crime groups illegally distributing prescription drugs.

Senator Kohl pushed Ms. Leonhart to provide comments on draft legislation he has sent to DEA that reduces the barriers patients in long-term care facilities face in order to receive their prescription pain medication.  In its current form, this draft legislation would grant nurses in long-term care facilities the ability to call in orders for controlled substances, including Schedule II drugs, pursuant to a consultation with the patient’s physician.  This legislation would also create a new registration category for nursing homes under DEA jurisdiction, which would require that they certify that all staff has received appropriate training.  Ms. Leonhart acknowledged that this is an important issue and DEA issued a policy statement on it, but will do more as soon as possible.  Senator Whitehouse signaled his support for Senator Kohl’s draft legislation and also chastised DEA for “standing in the way” of electronic prescribing (“e-prescribing”) of controlled substances, to which Ms. Leonhart noted she signed a e-prescribing statement of policy as Acting DEA Administrator, but she would continue to prioritize e-prescribing if she were confirmed.

One of the most interesting lines of questioning came from Senator Sessions, who asked Ms. Leonhart about her views on the legalization of marijuana and Mexican drug cartels.  Ms. Leonhart agreed with Senator Sessions that it is dangerous to legalize marijuana, because she feels that many people focus on the financial benefits of legalizing marijuana while ignoring the social costs of legalization.  She flatly stated that she would enforce federal drug laws in all areas regardless of state law.  Senator Sessions also asked Ms. Leonhart how DEA can help defeat Mexican drug cartels.  Ms. Leonhart did not have a specific answer to this question, but indicated that she thought more could be done by DEA, and she would do so if confirmed.