By Kurt R. Karst –      

FDA’s Office of Orphan Products Development (“OOPD”) surpassed the 2,000 orphan drug designation mark in 2009 and designated a near-record 160 products for orphan (i.e., rare) diseases and conditions.  FDA also approved 17 orphan products in 2009, according to data taken from OOPD’s new orphan drug designation database.  The 2009 orphan drug designation figure continues a trend in an increase in designations in recent years.  As we previously reported, in 2008, OOPD designated a record 165 products. 

The tables below illustrate OOPD’s designation and FDA’s orphan drug approval track record since the enactment of the Orphan Drug Act in 1983.

Coincidentally, the Tufts Center for the Study of Drug Development just issued an Impact Report (subscription required) analyzing orphan drug designations.  According to that report:

• During the 2000s, orphan products comprised 22% of all new molecular entities (NMEs) and 31% of all significant biologics (SBs) receiving U.S. marketing approval.

• Orphan products receiving priority review status rose from 35% of all orphan NMEs in 2000-02 to 50% in 2006-08; during the same time the share of orphan SBs receiving priority review status rose from 17% to 67%.

• While biotech firms during the 2000s garnered, on average, about one-third of all orphan drug approvals, they received just over 50% of orphan drug designations.

• Sponsors engaged in clinical development funded through orphan grants reported that 22% of their programs led to approvals, which compares with a clinical approval success rate of 16% among mainstream drug developers.

By Kurt R. Karst –      
 
Massachusetts-based The Medicines Company (“TMC”) has lost its latest battle with the U.S. Patent and Trademark Office (“PTO”) for a Patent Term Extension for U.S. Patent No. 5,196,404 (“the ‘404 patent”) covering ANGIOMAX (bivalirudin), a drug product FDA first approved late on Friday, December 15, 2000 under New Drug Application (“NDA”) 20-873.  The ‘404 patent expires on March 23, 2010, but is subject to a 6-month period of pediatric exclusivity that will expire on September 23, 2010, when generic competition is anticipated (notwithstanding the recent addition of two new patents to the Orange Book for ANGIOMAX).  As we previously reported, TMC submitted a PTE application to the PTO 62 days after FDA approved the company’s ANGIOMAX NDA.  Under 35 U.S.C. § 156(d)(1), the submission of a PTE application must occur “within the sixty-day period beginning on the date the product received permission under the provision of law under which the applicable regulatory review period occurred for commercial marketing or use” (i.e., within 60-days of the date of NDA approval).  In March 2002, and again in April 2007, the PTO denied the PTE request as untimely.  Since then, TMC has agressively – and thus far unsuccessfully – sought a PTE for the ‘404 patent at the PTO and on Capitol Hill (see our previous posts here, here, and here). 

As we recently reported, in December 2009, TMC submitted a Petition and a Request for Reconsideration of its PTE application to the PTO.  The Petition requested that the PTO suspend its regulations at 37 C.F.R. § 1.750 “to the extent they limit requests for reconsideration of patent term extension applications to a single submission within the times specified in the rule.”  TMC previously requested reconsideration of the PTO’s denial of a PTE for the ‘404 patent on the basis that the date of approval of the ANGIOMAX NDA was in fact first effective as of Monday, December 18, 2000, the next business day after the December 15, 2000 NDA approval.

The Request for Reconsideration requested the PTO to employ a “rule of construction” under which the Office would consider the 60-day PTE application submission period at 35 U.S.C. § 156(d)(1) to commence on the first business day after the day the FDA transmits notice of NDA approval of the drug product if that transmittal occurs after normal business hours.  In the case of the PTE application for the ‘404 patent covering ANGIOMAX, that would mean the 60-day period would have begun on December 18, 2000 and the PTE application would have been timely filed within 35 U.S.C. § 156(d)(1). 

Among other things, TMC argued that its Request for Reconsideration is “particularly appropriate in this case” given the PTO’s “newly announced approach to counting days under § 156(d)(1).”  The PTO, after being challenged as to the date on which the 60-day period at 35 U.S.C. § 156(d)(1) begins, ruled in the context of another PTE application that although the PTO had in some instances started counting the 60-day period on the date after NDA approval, “[b]y not counting the date of FDA approval as one of the sixty days included in the time period for filing a PTE application, the USPTO was failing to comply with section 156 and case law.” 

In its January 8, 2010 decision, the PTO granted TMC’s Petition, stating:

The USPTO is persuaded by Applicant's argument for suspension of Rule 750 under the terms of Rule 183. That latter regulation states: "In an extraordinary situation, when justice requires, any requirement of the regulations in this part which is not a requirement of the statutes may be suspended or waived by the Director or the Director's designee, sua sponte, or on petition of the interested party, subject to such other requirements as may be imposed." 37 C.F.R. § 1.183. Since the USPTO has corrected its methodology of counting the time period of 35 U.S.C. § 156(d)(1) to conform with the express language of the statute and first applied its corrected counting methodology in finally denying Applicant's PTE application, the USPTO finds that justice favors giving Applicant the opportunity to address the denial of its PTE application under the USPTO new counting methodology. Accordingly, Applicant's petition filed under Rule 183 to suspend Rule 750 is GRANTED. [(italics and emphasis in original)]

However, TMC ultimately lost when the PTO denied the company’s Request for Reconsideration:

Applicant raises numerous arguments why the USPTO should consider its PTE application for the ' 404 patent based on the regulatory review period for Angiomax® (bivalirudin) timely filed under section 156(d)(1). Distilling those arguments to their core, Applicant asserts that the 60-day time window of section 156(d)(I) should not commence until an applicant can "be deemed to be on notice" of the FDA approval. Request for Reconsideration at 11. Because the USPTO finds that the section 156(d)(1) expressly sets forth the trigger date for compliance with section 156(d)(1) as the date the applicant may commercially market or use the approved product, which is the date of NDA approval, and does not take an applicant's receipt of such notice into consideration, the USPTO considers Applicant's arguments to be unpersuasive. The present request for reconsideration of the denial of the PTE application for the '404 patent therefore is DENIED. [(emphasis in original)]

TMC’s latest loss at the PTO is unlikely to be the last we hear from the company on this topic.  A lawsuit against the PTO is not out of the question.  And although TMC’s efforts to lobby Congress to pass legislation that would amend 35 U.S.C. § 156 to permit the PTO to accept the late filing of a PTE application for the ‘404 patent have not yet been fruitful, we understand that a deal is in the works (or at least was until the Massachusetts election on Tuesday) to include a provision in the Health Care Bill that would extend the '404 patent. 

Hyman, Phelps & McNamara, P.C.’s Ricardo Carvajal will be speaking at FDLI’s upcoming Introduction to Food Law and Regulation: A Program on Understanding How the Government Regulates the Food Industry.  Mr. Carvajal will be presenting on food safety and unintended components/contaminants in food.  The conference is scheduled for January 25-26 at the Park Hyatt Hotel in Washington, DC.  This conference will be immediately followed by a second FDLI conference, Food Hot Topics, scheduled for January 27-28.  Registration information for both conferences is available here.

By Peter M. Jaensch –

On January 14, 2010, the U.S. Attorney’s Office for the District of Massachusetts issued a statement  announcing the charging of Doctor Scott Reuben, a former Chief of Acute Pain at Bay State Hospital in Springfield, Massachusetts, with one count of health care fraud (18 U.S.C. §1347), alleging that Dr. Reuben falsified medical research.

The Information filed in the case alleges that Dr. Reuben sought and obtained research funding to study drugs used in multimodal analgesia therapy from companies manufacturing such drugs. In his proposals to these companies, Dr. Reuben represented that he would perform clinical trials and present the results in an article for publication. However, the government alleges that he never enrolled any patients and simply fabricated his results, which he then presented as legitimate research. Although the government alleges an overarching course of conduct extending back to at least 1999, the specific charges are based on the defendant’s alleged fraud against Pfizer, Inc. in connection with a study of its drug Celebrex.

Dr. Reuben has entered a plea agreement with the government in which he agrees, among other things, to make substantial restitution to several pharmaceutical companies. The agreement has not yet been accepted by the court. What effect the revelation of this fraud may have in the wider healthcare and clinical research communities remains to be seen.

By Ricardo Carvajal –

While calling for further research on bisphenol A ("BPA"), a chemical used in the manufacture of some plastics, FDA has acknowledged that it has "some concern about the safety of BPA:" 

At this interim stage, FDA shares the perspective of the National Toxicology Program that recent studies provide reason for some concern about the potential effects of BPA on the brain, behavior, and prostate gland of fetuses, infants and children.  FDA also recognizes substantial uncertainties with respect to the overall interpretation of these studies and their potential implications for human health effects of BPA exposure.  These uncertainties relate to issues such as the routes of exposure employed, the lack of consistency among some of the measured endpoints or results between studies, the relevance of some animal models to human health, differences in the metabolism (and detoxification) of and responses to BPA both at different ages and in different species, and limited or absent dose response information for some studies.

FDA is pursuing additional studies to address the uncertainties in the findings, seeking public input and input from other expert agencies, and supporting a shift to a more robust regulatory framework for oversight of BPA to be able to respond quickly, if necessary, to protect the public.

In addition, FDA is supporting reasonable steps to reduce human exposure to BPA, including actions by industry and recommendations to consumers on food preparation.  At this time, FDA is not recommending that families change the use of infant formula or foods, as the benefit of a stable source of good nutrition outweighs the potential risk of BPA exposure.

The agency is directing consumers to a list of "reasonable steps families and parents can take to minimize exposure to BPA" issued by the Department of Health and Human Services ("HHS").  According to HHS, domestic manufacturers have largely abandoned the use of BPA in the manufacture of bottles and cups for infants.  With respect to liquid infant formula sold in cans, HHS made clear that "[i]nfant formula in this packaging can offer important health advantages for some infants, and the proven benefit of good nutrition outweighs the potential risk of BPA exposure."  With respect to powdered infant formula mix, HHS noted that it "typically has no detectable level of BPA."

FDA's statement that it is "supporting a shift to a more robust regulatory framework for oversight of BPA" is of special interest to manufacturers.  The current food contact uses of BPA were approved through the issuance of food additive regulations before the advent of the notification process currently used for food contact substances.  Food additive regulations are not specific to manufacturers; thus, any manufacturer can use BPA consistent with an approving regulation without notifying the agency.  Further, amending or revoking a food additive regulation requires FDA to engage in rulemaking.  In contrast, food contact notifications are specific to manufacturers, and FDA can deem a food contact notification to no longer be "effective" upon written notice to the notifier and publication of a Federal Register notice – a mechanism that is much less burdensome than rulemaking. 

By Susan J. Matthees –

In July 2008, we blogged about the U.S. District Court for the Central District of California’s decision that found Purely Juice, Inc. liable under the Lanham Act for false advertising related to its pomegranate juice product.  Last month, the U.S. Court of Appeals for the Ninth Circuit affirmed the lower court’s decision, meaning Purely Juice must pay POM Wonderful damages of over $1 million, attorneys fees of over $600,000, and a disgorgement of profits of over $300,000. 

Purely Juice’s appeal contended, in part, that the district court’s standard for purity interfered with the authority of FDA.  The Ninth Circuit stated “POM did not sue to enforce the FDCA, and the facts show no encroachment on the FDA’s authority.”  The Ninth Circuit also held that the district court did not err by finding the Purely Juice had the requisite knowledge that its product was not 100% pure pomegranate juice and without sugar added, and that the president and founder of Purely Juice was personally liable. 

By Susan J. Matthees & Anne Marie Murphy –

On January 13, FDA announced the availability of a new draft guidance document titled, Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Continuing Review After Clinical Investigation Approval.  Pursuant to FDA regulations 21 C.F.R. §§ 56.108(a) and 56.109(f), IRBs must have written procedures for, among other things, continuing reviews (at least annually) of IRB-approved clinical trials and  determining which of those studies require more frequent review.  The new guidance document outlines how IRBs can carry out these responsibilities and provides guidance on what information should be provided to the IRB to assist with continuing reviews.  In 2006, FDA announced an initiative to update its 1998 Information Sheets, which provide guidance to IRBs, Sponsors, and Investigators.  When finalized, the new guidance will supersede FDA’s Information Sheet, Continuing Review After Study Approval.  
  
To assist IRBs with their reviews, the draft guidance document includes a list of information that FDA recommends IRBs consider during the continuing review, e.g., summaries of subject withdrawals, summaries of complaints, and the current version of the protocol and informed consent documents in use.  For multi-center studies, “FDA recommends that sponsors provide IRBs directly with information from the entire study, data monitoring committee reports, and any other information about the test article.”  FDA also states that IRBs may have written procedures to delegate among individual IRB members portions of the IRB continuing reviews so that the workload is sufficiently distributed to allow efficient review. 

With regard to expedited procedures for continuing review, the document provides a discussion of two of the nine categories (published in the Federal Register, see 63 Fed. Reg. 60353, 60356 (Nov. 9, 1998)) of research eligible for the expedited review set forth in 21 C.F.R. § 56.110(b).  These two categories, categories (8) and (9), are the only categories that apply to continuing reviews.  Category (8) provides for expedited continuing review where the research is  permanently closed to new subjects, where no subjects have been enrolled and no additional risks have been identified, or where the remaining research is limited to data analysis.  Category (9) provides for expedited review where the research is not being conducted under an investigation new drug (IND) application or an investigational device exemption (IDE), expedited review categories (2) through (8) do not apply to the research, and the IRB has documented “that the research involves no greater than minimal risk to the subjects and no additional risks have been identified.” 

Pursuant to 21 C.F.R. §§ 56.108(a)(2) and 56.109(f), IRBs must determine the appropriate frequency of continuing reviews, i.e., identify studies that should be reviewed more frequently than annually.  The guidance document provides a list of factors that FDA recommends IRBs consider when determining the frequency of reviews.  These factors include the risks involved in the trials, vulnerability of the study population, experience of the investigators, the IRB’s history with the sponsor and/or investigator, and whether the studies involve novel therapies.   FDA recommends that IRBs “establish written procedures for informing investigators of the FDA’s regulations and the IRB’s own policies and procedures on continuing review requirements.” 

Other Clinical Trial-Related Developments:

On December 29, 2009, FDA announced a proposed rule that would amend the Agency’s informed consent regulations.  The Food and Drug Administration Amendments Act (FDAAA) § 801(b)(3)(A) amended the Public Health Service (PHS) Act to require that FDA promulgate regulations that would require the informed consent forms for “applicable” clinical drug trials  include a statement that clinical trial information has been or will be submitted to NIH/NLM for inclusion in the clinical trial registry databank (i.e., clinicaltrials.gov).  Although FDAAA § 801(b)(3)(A) requires this change for applicable drug trials only, FDA’s proposed rule would extend the change in the informed consent form requirements to applicable device trials as well. 

In October 2009, FDA announced the availability a guidance document titled, Guidance for Industry:  Investigator Responsibilities - Protecting the Rights, Safety, and Welfare of Study Subjects.  The guidance document provides information to investigators on how they can meet their responsibilities under 21 C.F.R. Parts 312 and 812 to both protect study participants and ensure the integrity of study data.  The guidance document covers topics such as delegation of study-related tasks among the trial staff, training of trial staff, supervision of the trial, investigators’ oversight responsibilities, medical care made available to study participants, and investigator responsibilities towards protocol violations that represent unreasonable risks.  This guidance document finalizes a draft guidance that was published in May 2007.  

By Peter M. Jaensch –
 
On January 14, 2010, the United States District Court for the District of Columbia issued a decision in Smoking Everywhere, Inc. and Sottera, Inc. d/b/a NJOY v. United States Food and Drug Administration, et al., in which the court granted the plaintiffs’ motion for a preliminary injunction, thereby enjoining FDA from regulating electronic cigarettes as drug-device combination products.  E-cigarettes, which are packaged to look and feel like real cigarettes, are intended to replicate smoking by vaporizing a nicotine liquid that the user then inhales – a process users call “vaping.”

The case arises from detentions imposed by FDA on the import of electronic cigarettes, which FDA contends are drug-devices under the FDCA and therefore subject to FDA regulation. The court concluded that treating e-cigarettes as drug-device combination products, rather than tobacco products, was unlawful, absent a showing that the products are intended to assist in treating nicotine addiction or to “affect the structure or function of the body in a way distinguishable from ‘customarily marketed’ tobacco products.” The court believed that doing so would frustrate Congress’ clear intent to distinguish FDA’s regulation of drugs and devices from its regulation of tobacco products.

The court did not opine whether FDA could regulate e-cigarettes under the Family Smoking Prevention and Tobacco Control Act, which was signed into law after the FDA detention had been imposed.  It would appear that FDA lacks such authority until it issues a regulation bringing e-cigarettes under its jurisdiction as tobacco products.

The decision holds out the potential for a far wider significance with regard to all products regulated by FDA.  In footnote 8, the court analyzes and rejects FDA’s position that its import decisions are unreviewable by courts. The ruling on this point will undoubtedly suggest that other importers of a variety of products regulated by FDA will sue FDA to challenge import decisions or at least use the threat of a suit as leverage to get FDA to allow imported products into the U.S.

By Kurt R. Karst –      

As we reported yesterday, the Federal Trade Commission (“FTC”) held a press conference on January 13, 2010 announcing the release of a report, titled “Pay-for-Delay: How Drug Company Pay-Offs Cost Consumers Billions,” on the effects of pay-for-delay deals in the drug industry over the past 6 years.  FTC Chairman Jon Leibowitz and Commissioner J. Thomas Rosch issued separate statements (here and here) about the report.  The FTC also announced the creation of a new pay-for-delay website providing information about the FTC’s work in the area of branded and generic drug competition.

The report, which has been timed to urge Congress to include pay-for-delay provisions in the Health Care Bill, estimates that pay-for-delay agreements “cost American consumers $3.5 billion per year – $35 billion over the next 10 years.”  The report concludes that “a legislative solution offers the quickest and clearest way to deter these agreements and obtain the benefits of generic competition for consumers.”  

The FTC report notes that although the U.S. Court of Appeals for the Sixth Circuit  held in 2003 that such agreements were per se illegal (In re Cardizem CD Antitrust Litigation, 332 F.3d 896 (6th Cir. 2003)), subsequent appellate court decisions upholding such agreements (Schering-Plough Corp. v. Fed. Trade Comm’n, 402 F.3d 1056 (11th Cir. 2005); In re Tamoxifen Citrate Antitrust Litigation, (2d Cir. 2006); In re Ciprofloxacin Hydrochloride Antitrust Litigation, 544 F.3d 1323 (Fed. Cir. 2008)) have led to their increasing use, as shown in the following table from the report:

(Information in the table above is based on submissions made to the FTC required by the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (“MMA”).  The MMA requires pharmaceutical applicants – both brand and generic – to file with the FTC and the Assistant Attorney General certain agreements executed on or after January 7, 2004.  Since the enactment of the MMA, the FTC has published summaries of these agreements.  Copies of previous summaries are available here.)

The FTC reportedly has “multiple investigations underway,” and has filed complaints opposing pay-for-delay arrangements concerning generic ANDROGEL (testosterone gel) (Fed. Trade Comm’n v. Watson, No. 09-cv-00598 (N.D. GA Feb. 9, 2009) (transfer order)) and PROVIGIL (modafinil) (Fed. Trade Comm’n v. Cephalon, No. 08-cv-2141-RBS (E.D. Pa. May 8, 2008) (transfer order)), respectively. 

Other findings discussed in the report include the following:

• “Agreements with compensation from the brand to the generic on average prohibit generic entry for nearly 17 months longer than agreements without payments, where the average is calculated using a weighted average based on sales of the drugs.”

• “From FY2004-FY2009, 66 final agreements involved some form of compensation from the brand to the generic combined with a delay in generic entry.”

• “Out of the 66 agreements that combined compensation from the brand to the generic with deferred generic entry, 51 agreements (77%) were between the brand pharmaceutical company and the generic company that was the first to seek entry prior to patent expiration for the relevant brand-name drug.”

• “From FY2004-FY2009, pharmaceutical companies filed a total of 218 final settlement agreements involving brand and generic companies. Seventy percent of those patent settlements – 152 – did not involve compensation from the brand to the generic combined with a delay in generic entry.”

• “About 25% of patent settlement agreements from FY2004-FY2008 that were with first-filer generics involved an explicit agreement by the brand not to launch an AG to compete against the first filer, combined with an agreement by the first-filer generic to defer entry past the date of the agreement.”

By Cassandra A. Soltis –

The Federal Trade Commission ("FTC") made clear in a recent opinion that the Federal Food, Drug, and Cosmetic Act ("FDC Act") is not binding on the Commission in its enforcement of Sections 5 and 12 of the Federal Trade Commission Act (FTC Act).  The Commission also addressed some First Amendment issues and described the type of substantiation necessary when making certain health-related efficacy claims.

The FTC upheld charges against Daniel Chapter One and James Feijo (the "Respondents") for unsubstantiated claims that the Respondents’ dietary supplements would prevent, treat, or cure cancer or tumors and other serious illnesses.  In the Matter of Daniel Chapter One and James Feijo, No. 9329 (Dec. 18, 2009), at 1.  The Commission disagreed with the Respondents’ argument that the claims made for the products were protected by the First Amendment because they were ideas or opinions about the products’ efficacy, stating that “Respondents made assertions not just about what they believed those products might do, but represented that the [dietary supplements] would in fact treat or cure cancer, prevent or shrink tumors, and ameliorate the side effects of radiation and chemotherapy.”  Id. at 12.  Furthermore, the FTC noted that the representations “constituted commercial speech, not simply practicing religion or engaging in ‘charitable solicitations,’” as the Respondents suggested.  Id. at 13.  The Commission indicated that because the speech in question was commercial in nature and false or misleading, it is not afforded First Amendment protection.  Id. at 14. 

The Commission also disagreed with the Respondents’ claim that the representations made for the dietary supplements were immune from FTC challenge because they were structure/function claims, as defined in the Dietary Supplement Health and Education Act ("DSHEA"), which amended the FDC Act.  Id. 16.  The FTC stated that the representations were not structure/function claims, and even if they were, DSHEA requires that they be truthful and not misleading and supported by adequate substantiation.  Id.  The Commission concluded that “even if the [FDC Act] departed from the FTC Act and its relevant case law, Respondents offer no authority that it would be binding on the Commission.”  Id.

According to Dr. Dennis Miller, who was the FTC’s expert and a board-certified pediatric hematologist/oncologist, in order to support a claim that a product “treats, cures, or prevents cancer, the products’ efficacy and safety must be demonstrated through controlled clinical studies (tests on humans).”  Id. at 18.  Dr. Miller also indicated that studies performed on animals or in test tubes are insufficient and that “the need to substantiate a claim by clinical studies (i.e., on humans) was the same whether the purported agent was a herbal medicine or a more conventional pharmaceutical agent.”  Id.

Dr. Miller concluded that the reference materials relied on by the Respondents “did not constitute competent and reliable scientific evidence that any of the [dietary supplements] prevent, treat or cure cancer; that most of those materials were not peer-reviewed papers but instead consisted of author opinions and literature reviews; that many of the studies involved in vitro or animal studies, not studies on humans; that [other reference materials] relied on the efficacy or safety of ingredients of the [dietary supplements] rather than the products themselves” and that, without evidence that the dietary supplements “contained exactly those ingredients in the proportion tested, those studies were not probative; and that there is no competent and reliable scientific evidence that the [dietary supplements] are effective, either alone or in combination with” the other products sold by the company.  Id. at 18-19.  For those reasons and others, the Commission denied the Respondents’ appeal and issued a final Order requiring the Respondents to cease certain practices. 

By Kurt R. Karst –      

Over the past several weeks, proponents of a ban on so-called pay-for-delay settlements have put a full-court press on Congressional leaders to include provisions in the final Health Care Bill.  The House bill  includes a provision (§ 2573) sponsored by Bobby Rush (D-IL) that would amend the FDC Act to add section 505(w) – “Protecting Consumer Access to Generic Drugs” – to, among other things, make it unlawful for any person from being a party to any agreement resolving or settling a patent infringement claim in which an ANDA applicant receives anything of value, and the ANDA applicant agrees not to research, develop, manufacture, market or sell the generic drug that is the subject of a patent infringement claim.  The Senate bill does not include a pay-for-delay provision sponsored by Sen. Herb Kohl (see our previous post here).

In late December 2009, several Senators wrote a letter to Senate leaders asking for the final Health Care Bill to include the House bill’s ban on pay-for-delay settlements.  “By adopting this provision, conferees can significantly address the rising costs of prescription drugs.  These ‘pay for delay’ agreements between brand name and generic drug companies deny consumers the benefits of generic drug competition,” according to the letter. 

On January 11, 2010, the American Antitrust Institute (“AAI”), among several other organizations, wrote a letter to Senate Majority Leader Harry Reid (D-NV) and House Speaker Nancy Pelosi (D-CA) encouraging inclusion of the Rush amendment in the final Health Care Bill, as well as the Drug Price Competition Act of 2009, which was introduced last year by Sen. Bill Nelson (D-FL), and in the house by Rep. Alcee Hastings (D-FL).  That bill would amend the definition of “first applicant” at FDC Act § 505(j)(5)(B)(iv)(II)(bb) with respect to 180-day exclusivity eligibility so that certain subsequent ANDA applicants could trigger and be eligible for exclusivity (see our previous post here).  According to the AAI letter:

[Pay-for-delay] payments are anticompetitive and should be considered per se illegal: they prevent any generic manufacturer with a legitimate challenge to a patent from potentially entering the market. . . . 

Expanding the exclusivity period is vitally important, since it removes the barrier to entry that has protected collusive settlements between brands and first-filing generics. Including this language in the final health reform legislation would provide a strong complement to Representative Rush’s per se ban on these payments.

Now it is the Federal Trade Commission’s (“FTC’s”) turn to put on the pressure.  On January 12, 2010, the FTC announced that it will hold a press conference at the Rayburn House Office Building on January 13, 2010 “to announce an FTC staff analysis showing that pay-for-delay deals between brand and generic drug companies are costing American consumers billions a year, and to encourage inclusion of the House-passed pay-for-delay provision in the final version of the health care reform bill.”  The FTC – and FTC Chairman Jon Leibowitz in particular – has made no bones about its opposition to pay-for-delay settlements.  In June 2009, Chairman Leibowitz said in a speech that eliminating “pay-for-delay” settlements could save consumers $3.5 billion annually.

By Ricardo Carvajal –

Californians won’t have to contend with this warning in their grocery stores – for now.  A California appellate court has upheld a lower court’s ruling that the Federal Meat Inspection Act (FMIA) preempts Proposition 65 point-of-sale warning requirements for meat.  The suit was filed by trade associations for the meat industry in response to notices of violation sent to meat processors and retailers by a California citizen.  Proposition 65 requires that such a notice be provided before the filing of a citizen suit to enforce that law.  The notices contended that certain meat products containing dioxins and PCB’s, both of which have been identified as carcinogens under Proposition 65, were being sold without a Proposition 65 warning (PCB’s are also listed as reproductive toxins).  Proposition 65 requires that a “clear and reasonable” warning be provided before consumers are exposed to a chemical “known to the state to cause cancer or reproductive toxicity.”  The trade associations sought a declaratory judgment that Proposition 65 is preempted by the FMIA.
 
The trial court granted summary judgment for the trade associations, and ruled that Proposition 65 was impliedly preempted by the FMIA.  The appellate court upheld the grant of summary judgment on the ground that Proposition 65 is expressly preempted by the FMIA.  The appellate court decision is worth reading for its extensive discussion of the scope of “labeling” as that term is used in the FMIA, FDCA, and FIFRA.  Based on its reading of those statutes and applicable judicial precedents, the appellate court concluded that the FMIA expressly preempts a Proposition 65 point-of-sale warning requirement because that warning would constitute “labeling” that is in addition to, or different than the FMIA's labeling requirements.  The appellate court relied on the definition of "labeling" in FDCA section 201(m), as interpreted by the United States Supreme Court in Kordel v. United States, 335 U.S. 345 (1948) (material constitutes labeling if it bears a “textual relationship” to the product, “supplements or explains” the product, and is “designed for use in the distribution and sale” of the product).  No word yet on whether there will be an appeal.

By Peter M. Jaensch –

On January 4, 2010, the Washington Legal Foundation (“WLF”) filed an amicus curiae brief in support of Ortho Biotech Products’ petition for a writ of certiorari in the Supreme Court of the United States, urging review of the decision in United States, ex rel. Mark Eugene Duxbury v. Ortho Biotech Products, L.P., 579 F.3d 13 (1st Cir. 2009).

As discussed in our earlier post, the underlying case asserted qui tam claims under the False Claims Act (“FCA”) against Ortho Biotech that were based on certain of the company’s product promotion activities, alleging promotion of off-label use, marketing the “spread” and providing “kickbacks” to providers in the form, among others, of free product samples.  The District Court dismissed all of the claims, citing multiple grounds.  On appeal, the First Circuit reversed in part, reviving only those claims attributable to Duxbury based on kickbacks.  Ortho Biotech petitioned for certiorari to the Supreme Court on December 3, 2009.  Such petitions are formal pleadings requesting the Court to exercise its discretion to review a lower court's decision, and are rarely granted.

As an amicus in support of Ortho Biotech’s petition, WLF argues that the FCA is meant to combat fraud, not legitimate product promotion, and that it cannot have been Congress’ intent to permit private suits against pharmaceutical and medical device companies for their truthful promotional activities absent the identification of any fraudulently-filed claim.  Ultimately, WLF argues the specific allegation of an actual false claim is a “threshold issue” without which Federal Rule of Civil Procedure 9(b) is dispositive, and requires dismissal of Respondent’s claims.  This argument is buttressed with a warning that, if unreviewed, the Duxbury decision threatens the ability of drug and medical device manufacturers to discuss freely and truthfully their products’ off-label uses and to distribute drug samples – activities which are beneficial to doctors and their patients.

By Dara Katcher Levy –

On December 23, 2009, FDA filed a Motion To Dismiss the First Fishery import matter that we previously blogged about back in late October.  In short, First Fishery had filed suit seeking declaratory judgment and injunctive relief with regard to its product’s placement on Import Alert 99-08 – Detention Without Physical Examination of Processed Foods for Pesticides.  First Fishery alleged that a finding of pesticide in its product was subject to an exemption under the Federal Food, Drug, and Cosmetic Act, and that there had been no final determination by FDA that the sampled product was violative before placing the product on Import Alert..

In its Motion to Dismiss, FDA acknowledges that in November, after correspondence with First Fishery and with the EPA (and after the First Fishery lawsuit was filed), FDA voluntarily released the detained entry and on December 3, 2009, removed the product from Import Alert.  Because of these actions, FDA asserts there is no remaining case or controversy and moves to dismiss.

This case is a prime example that, although FDA may have broad discretion over imports, an appropriate legal challenge in the correct circumstance may force FDA to rein itself in. 

By William T. Koustas –

In yet another twist in the debate regarding FDA’s use of Risk Evaluation and Mitigation Strategies (“REMS”), Kaiser Permanente (“Kaiser”), which is the largest private integrated health care delivery system in the U.S., submitted a citizen petition on December 22, 2009 requesting FDA take several actions in order to mitigate concerns it has with FDA’s implementation of REMS, specifically Elements to Assure Safe Use (“ETASU”). 

In its citizen petition, Kaiser notes that § 505-1 of the Federal Food, Drug and Cosmetic Act (“FDCA”) requires FDA to obtain input from health care providers, patients, etc. with regard to ETASU in order to ensure that a REMS is not unduly burdensome to the patient and to minimize the burden on the health care system.  However, with the exception of REMS for extended-release opioids, Kaiser claims that FDA has not publicly sought input from patients or health care providers on the implementation of REMS as required by § 505-1.  Kaiser further claims that REMS, especially those with ETASU, can add a significant burden to the delivery of health care and thus potentially increase the cost of REMS such that it outweighs the benefits.  As a consequence, Kaiser believes that health care providers and insurers should be consulted before a new REMS with ETASU is implemented.

Kaiser discusses five actions it would like FDA to take in order to minimize the burden of ETASU on health care providers as well as ensuring that they have a voice in the implementation of REMS.  First, Kaiser requests that FDA “increase transparency and opportunity for public comment in the development, implementation and assessment of REMS programs.”  As such, Kaiser would like FDA to provide increased opportunity for public comment on all REMS with ETASU; however, Kaiser also envisions FDA establishing an advisory committee dedicated to the review of ETASU.  In the interim, Kaiser suggests that advisory committees (with a health care provider member) reviewing drugs that will likely receive ETASU also have input on the ETASU itself.  Kaiser argues that this type of input before an ETASU is implemented could reduce the likelihood that the program will need to be altered later as well as lessening the burden on the health care system.

Second, Kaiser would like FDA to make de-identified data collected through the use of ETASU publically available, which would permit health care providers, and other parties, to identify the effectiveness of REMS. 

Third, Kaiser requests that FDA evaluate the effectiveness of ETASU that have been in effect for at least one year and extend that evaluation process to all ETASU on an annual basis.  Kaiser argues that this will ensure that the benefits of the REMS will continue to outweigh the cost to patients and the health care provider while also ensuring its success. 

Fourth, Kaiser’s citizen petition raises the issue of manufacturers using ETASU to limit access of a drug to certain health care providers.  Kaiser acknowledges that an ETASU may require that some drugs only be dispensed by certified pharmacies, but it argues that manufacturers have used this requirement to prevent or limit some health care providers from using their own facilities by refusing to certify them despite the fact that these pharmacies are otherwise qualified to dispense the drug.  According to the citizen petition, some manufacturers have refused to certify a Kaiser pharmacy for no reason other than the fact that the manufacturer has “contracted” with a specialty pharmacy, thus permitting manufacturers to dictate who can prescribe and dispense a drug with ETASU. 

Finally, Kaiser would like FDA to ensure that REMS are implemented in a way to protect patient health information.  Specifically, Kaiser expresses concern that patient enrollment forms for REMS include an authorization for disclosure of such information to third parties and some enrollment forms make receiving the drug contingent on patients accepting this.  Kaiser suggests that this concern could be alleviated if manufacturers were required to identify all entities they distribute patient information to as part of the regular REMS assessments.