By Peter M. Jaensch –

On March 23, 2010, Congressman Jason Chaffetz (R-UT) introduced H.R. 4913 – the Free Speech About Science Act of 2010.  The bill proposes several amendments to FDC Act § 403(r) concerning the misbranding of foods, which would have the effect of expanding authority to include disease and health-related condition claims in the labeling of some foods and dietary supplements.  According to Rep. Chaffetz, “[t]he bill allows the producers of healthy foods and dietary supplements to cite legitimate scientific studies on the health benefits of their products.”

H.R. 4913 creates a new subsection of FDC Act § 403(r)(3) to permit food labeling to include disease and health-related condition claims, notwithstanding certain existing limitations, where the claim is based on “legitimate scientific research,” provides a balanced summary of the research, and is written in a way that enables the public to understand it.

The bill also reformats and adds a new subsection to FDC Act § 403(r)(6) permitting claims “to diagnose, mitigate, treat, cure, or prevent a specific disease or class of diseases” in labeling for dietary supplements where the claim is based on “legitimate scientific research,” is truthful and not misleading, and explicitly disclaims prior evaluation by FDA. Such changes would permit food and dietary supplement manufacturers to make claims similar to those typically made for drug products, without subjecting them to the same degree of oversight or requiring the same depth of scientific analysis.

For both food and dietary supplements, H.R. 4913 requires that the claim must cite to the research source and identify parties funding the research.

H.R. 4913 also precludes the Secretary of Health and Human Services from taking any action to restrict the dissemination of the information that “is not false or misleading on legitimate scientific research” in connection with food sales.

The amendments largely turn on the basis in “legitimate scientific research,” which the bill defines as “scientific research” that is performed “in vitro, in vivo, in animals, or in humans,” is conducted in accord “with sound scientific principles,” has been “evaluated and accepted by a scientific or medical panel,” and has been published in a peer-reviewed article or book, recognized textbook, peer-reviewed scientific publication or any U.S. Government publication.

The bill is co-sponsored by Rep. Jared Polis (D-CO), and was referred to the House Committee on Energy and Commerce.

By Kurt R. Karst –   

Earlier today, The Medicines Company (“MDCO”) announced that the company filed a new Administrative Procedure Act (“APA”) lawsuit in the U.S. District Court for the Eastern District of Virginia (Alexandria Division) challenging the Patent and Trademark Office’s (“PTO”) March 19, 2010 decision denying a Patent Term Extension (“PTE”) for U.S. Patent No. 5,196,404 (“the ‘404 patent”) covering MDCO’s ANGIOMAX (bivalirudin) drug product.  This is the second MDCO lawsuit over the issue. 

On March 16, 2010 Judge Claude M. Hilton of the U.S. District Court for the Eastern District of Virginia (Alexandria Division) issued an opinion vacating the PTO’s earlier denial of a PTE for the ‘404 patent and remanded the case to the PTO for further consideration.  (See our previous post here)  The PTO’s March 19th decision – issued less than three days after Judge Hilton remanded the case to the PTO (an amazing feat of government efficiency!) – rejected MDCO’s proposed “rule of construction” under which the PTO 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 (i.e., after 4:30 PM east coast time in some cases).  Briefly, in the case of the PTE application for the ‘404 patent, that would mean the 60-day period would have begun on Monday, December 18, 2000 and the PTE application would have been timely filed within 35 U.S.C. § 156(d)(1), rather than on Friday, December 15, 2000 when FDA issued its approval letter (at 5:18 PM) for the ANGIOMAX NDA (NDA No. 20-873).

The day before issuing its PTE denial, the PTO issued an interim PTE (61-days) (later corrected) consistent with Judge Hilton’s order that the PTO “take such actions as necessary to ensure that the ‘404 patent does not expire pending further resolution of these proceedings.”  Absent the interim PTE, the ‘404 patent would have naturally expired on March 23, 2010.  Unless the PTO’s latest decision is vacated, the PTO is presumably unable to issue another interim PTE given the Federal Circuit’s 2007 decision in Somerset Pharmaceuticals v. Dudas that an interim PTE is not available when the PTO has already denied a PTE application. 

The PTO reasoned in its March 19th decision that a “calendar day” rather than a “business day” construction of the PTE statute (35 U.S.C. § 156(d)(1)) is appropriate because, among other things, MDCO’s construction would create disharmony with FDA’s interpretation of 35 U.S.C. § 156(g)(1)(B)(ii).  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).  Under 35 U.S.C. § 156(g)(1)(B)(ii), for purposes of calculating the PTE “regulatory review period,” the approval phase begins on the date the NDA application was initially submitted under FDC Act § 505 for the approved product and ends “on the date such application was approved under such section.”

MDCO alleges in its latest lawsuit that the PTO’s March 19th decision violates the APA for a litany of reasons.  Specifically, that the decision:

• Disregards the District Court's March 16 Opinion;
• Disregards the text, strcture, and purpose of 3S U.S.C. § 156(d)(1);
• Ignores and conflicts with the remedial purposes of the Hatch-Waxman Act;
• Adopts a statutory interpretation that would produce absurd consequences;
• Adopts a statutory interpretation that would deprive applicants of the full 60-day period provided by statute to prepare and file a [PTE] application;
• Fails generally to provide a reasoned explanation for the decision it reaches;
• Erroneously relies on inapposite cases;
• Fails to adequately explain the inconsistency between the interpretation of the phrase “beginning on the date” as applied by the FDA and PTO under the same statute;
• Fails to provide a reasoned explanation of the purported difficulties of administering a "business day" rule;
• Erroneously claims to be adhering to a "historic practice";
• Misconstrues and fails adequately to respond to MDCO's arguments;
• Fails to explain its departure from past PTO precedent; and
• Erroneously relies on irrelevant factors.

Among other things, MDCO asks the court to vacate the PTO’s March 19th PTE denial and declare that the company timely filed its PTE application, and order the PTO to “immediately” grant an interim PTE for the ‘404 patent “and to take any additional present or future actions as are necessary to enable MDCO to protect its rights and to ensure that [the ‘404 patent] does not expire prior to issuance of a certificate of extension.”

By Ricardo Carvajal –

In a recently issued guidance document, FDA makes clear that a company with a reportable food located in multiple facilities can submit a single report to the Reportable Food Registry (RFR) instead of individual reports for each facility (a reportable food is a food for which there is a reasonable probability that the use of, or exposure to, such article of food will cause serious adverse health consequences or death to humans or animals).  FDA had indicated in a previous guidance document that a responsible party (the person who submits the facility's registration) can authorize an individual to submit a report to the RFR on the responsible party's behalf.  The new guidance document makes clear that a single report can cover multiple facilities within the same company.

By Alan M. Kirschenbaum & Kurt R. Karst –

On March 23, 2010, President Obama signed into law the Patient Protection and Affordable Care Act (“PPACA”) (Pub. L. No. 111-148 ).  A companion bill, the Health Care Education Affordability Reconciliation Act of 2010 (H.R. 4872), which the House of Representatives passed (along with PPACA) on March 21st, is currently under consideration by the Senate, and contains amendments to PPACA that reconcile the Senate and House versions of the legislation.

Hyman, Phelps & McNamara, P.C. has prepared a memorandum – available here – that focuses on the provisions that most directly affect pharmaceutical and medical device manufacturers.  In light of the importance of this legislation, we have prepared this memorandum despite the fact that the Senate has not yet passed the companion bill, H.R. 4872.  The HP&M memorandum describes provisions of PPACA as it will be amended by H.R. 4872 if the latter passes the Senate in current form.  It is possible, though unlikely, that provisions of H.R. 4872 described in the memorandum will be amended in the Senate.  In that event, we will post an update describing the pertinent changes.

UPDATE:

Our original memorandum on the Patient Protection and Affordable Care Act posted on Wednesday evening (March 24) was updated on Thursday morning (March 25) to correct an error on page 8 (excise tax on devices).  We apologize for any confusion.

By Kurt R. Karst –      

Just days after Judge Claude M. Hilton of the U.S. District Court for the Eastern District of Virginia (Alexandria Division) issued his opinion and order vacating the Patent and Trademark Office’s (“PTO’s”) denial of 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) and remanding the case to the PTO for further consideration, the PTO, on March 19, 2010, once again denied MDCO’s PTE application in a 15-page decision (accompanied by more than 300 pages of attachments).  Heeding Judge Hilton’s order to “take such actions as necessary to ensure that the ‘404 patent does not expire pending further resolution of these proceedings,” and at the same recognizing the Federal Circuit’s 2007 ruling in Somerset Pharmaceuticals v. Dudas that an interim PTE is not available when the PTO has already denied a PTE application, however, the PTO’s March 19th denial was preceded by a March 18, 2010 decision (here and here) granting MDCO an interim PTE  until May 23, 2010 for the '404 patent.

As we previously reported, Judge Hilton’s March 16, 2010 decision stems from a January 2010 Complaint and Motion for Summary Judgment following the PTO’s January 8, 2010 denial of MDCO’s December 2009 Request for Reconsideration asking 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 (i.e., after 4:30 PM east coast time in some cases).  In the case of the PTE application for the ‘404 patent covering ANGIOMAX, that would mean the 60-day period would have begun on Monday, December 18, 2000 and the PTE application would have been timely filed within 35 U.S.C. § 156(d)(1), rather than on Friday, December 15, 2000 when FDA issued its approval letter for the ANGIOMAX NDA (NDA No. 20-873) – albeit at 5:18 PM on that day. 

Judge Hilton in his 18-page opinion, which tracks MDCO’s briefs in the case, explained that the PTO erroneously believed that the Office’s construction of the term “date” in 35 U.S.C. § 156(d)(1) to mean “calendar day” was compelled by the PTE statute and that the Office lacked any discretion to adopt MDCO’s “business day” construction.  Judge Hilton also identified several arguments that MDCO made to support its “business day” construction – i.e., that the focus of 35 U.S.C. § 156(d)(l) is “on the date approval was received, the purpose of § 156(d)(1), the need to ensure that all applicants received the 60 days to file extension applications that Congress required[,] and the ways in which [MDCO’s] interpretation of date in combination with its new counting rule is inconsistent with that requirement” – and faulted the PTO for not considering them and for not providing an analysis of the Office’s plain meaning definition of the term “date” as “calendar day.”

The PTO’s March 19th decision expressly considers each one of these points (although previous decisions appear to have discussed them as well, but not in such detail).  Here are some tidbits from the PTO’s decision:

• The date stamped on the FDA approval letter covers a calendar day. . . . Congress has not restricted the FDA to approve drugs before a certain time of day such as 4:30 p.m., the cut-off time that Applicant advocates here. Applicant's position that approval must occur on a business day, prior to 4:30 p.m. east coast time, in order to be deemed effective on that day is consequently not supported by statute. Nor does it make sense for the FDA to limit its approval window to a few hours in a day.  Because Applicant essentially argues that FDA must stop official business at 4:30 p.m. east coast time, including halting the review of applications, Applicant's position could also prolong the approval process – to the detriment of industry and the public.

• MDCO isolates the word "received" from section 156(d)(1) and contends that it shows that Congress intended for the patentee to have constructive receipt of the FDA approval before triggering the 60-day filing window.  In Applicant's view, "an after-hours communication should be deemed to have been received on the next business day."  The presence of the word "received" in section 156(d)(1), however, must be read in context. The statute speaks in terms of the "product receiv[ing] . . . permission for commercial marketing or use." The statute says nothing about the patentee actually or constructively receiving notice of the FDA approval. Hence, Applicant's argument is not fully consistent with the statutory language of section 156(d)(1). In fact, . . . one reason why the term "received" in section 156(d)(1) cannot refer to the actual, or even constructive, receipt of an approval letter is because some permissions within the scope of section 156(d)(I) do not come in the form of approval letters at all. See, e.g., 35 U.S.C. § 156(g)(2)(B)(ii) (specifying that the regulatory review period for a food or color additive ends on the effective date of a regulation).

• The patent law includes various time periods (other than the one at issue) that are measured from events or actions that do not take place in the USPTO, for example, the publication of a description of the invention, the public use of an invention, the placement of an invention on sale, the filing of an application in a foreign country.  In all instances, the USPTO uses the calendar date for all trigger dates.  Regarding the actions that the USPTO itself takes, the agency, like the FDA, is not limited to "business hours."

• The USPTO acknowledges that the FDA uses the 4:30 rule in the limited context of electronic submissions to determine when a new drug application is submitted, but the FDA does not use that same rule when assessing the date that same application is approved. . . .  The FDA only applies the 4:30 rule to the beginning date.  That beginning date is not relevant to the 60-day filing window provided in section 156(d)(1) because the date an applicant submits a new drug application to the FDA is unrelated to a time period that turns on a subsequent approval of that application. Instead, it is the ending date in section 156(g)(1)(B)(ii) that is relevant to 60-day filing window of section 156(d)(1) because the conclusion of the review period marks the beginning PTE application filing window. . . .  [T]he USPTO concludes that the best approach is to interpret section 156( d)' s date language in harmony with the FDA's approach to interpreting the ending date language in section 156(g)(1)(B)(ii).

• Beyond the disharmony it would create with the FDA's interpretation of section 156(g)(1)(B)(ii), there are other problems with MDCO's arguments in favor of the 4:30 rule. First, the FDA's refusal to accept new drug application submissions after 4:30 p.m. bears no logical connection to whether a facsimile transmission sent after that time is received on the same calendar day. . . .  Second, the FDA was conducting business after 4:30 p.m. on December 15,2000, and any other time it takes action. . . .  Third, MDCO fails to consider that a 4:29 p.m. approval would deprive an applicant for a patent term extension of the full 60-day period just as much as a 4:31 p.m. approval.  Finally, . . . [h]ad the FDA notified MDCO of the approval of its drug via postal mail only, MDCO could not allege that the term "date" in section 156(d)(l) means "business day" because there would be no after business hours transmission of approval from the FDA to quibble over. Thus, this entire litigation was made possible solely because the FDA chose to extend a courtesy to MDCO and provide as prompt notification of FDA approval as possible.

• [T]here are indeed many instances where the USPTO prevents loss of rights due to an applicant, appellant, or patentee's failure to meet certain deadlines. But in all of those cases, Congress has provided the avenue for the relief available at the agency, and thus to the applicant or patentee. In light of that, it speaks volumes that Congress provided no avenue to allow the USPTO to accept a late PTE application filed under section 156. Given Congress's unquestionable awareness that lawyers make mistakes, and the various provisions it provided to redress those mistakes, Congress's failure to include a similar provision related to the section 156(d)(1) 60-day filing window compels the conclusion that Congress did not intend the provision to be remedial, or to be interpreted in a way that benefits late-filing PTE applicants.

And perhaps one of the most important general points . . . .

• [A] PTE application is a relatively short filing. The statute requires only certain minimal items of information. See 35 U.S.C. § 156 (d)(1)(A)-(E).  Consequently, it is not as if a patent owner needs a full 60-days to assemble an of the necessary information and/or prepare the application. In fact, all the information that MDCO needed, except for its FDA approval, was – available well before December 15,2000.  And on December 15,2900, MDCO received the missing FDA approval.  Thus, MDCO was equipped on December 16, 2000, to file its PTE application.  An applicant for PTE gains no advantage, nor does it receive any additional restored term, by waiting to the last minute to file its PTE.

Apparently outraged at the PTO’s efficiency in expeditiously issuing its denial a mere 72 hours after Judge Hilton’s decision, MDCO’s CEO told the New York Times “Now I’m at war; this is very disconcerting . . . . It’s not even polite, you know what I mean?”

MDCO will almost definitely challenge the PTO’s latest denial.  Absent the interim extension, the ‘404 patent would expire on March 23, 2010.  (The patent is also subject to a 6-month period of pediatric exclusivity.)  Depending on when the case is resolved, additional interim PTEs may follow. 

By Jamie K. Wolszon & David B. Clissold –

FDA published two Federal Register notices Friday, March 19th related to its oversight and regulation of cigarettes and smokeless tobacco, including a much heralded final rule to restrict the sale of cigarettes and smokeless tobacco to children, and an advanced notice of proposed rulemaking asking for comment on potential outdoor advertising restrictions such as requiring stores to post graphic anti-tobacco messages.  The notice regarding outdoor advertising restrictions likely will intensify debate about the constitutionality under the First Amendment of FDA's proposed restrictions on commercial speech.

FDA’s final rule is intended to reduce the appeal of cigarettes and smokeless tobacco to children and to make it difficult for children to access cigarettes and smokeless tobacco.  Among other things, the rule would prohibit: the sale of cigarettes or smokeless tobacco to people younger than 18; the sale of cigarette packages with less than 20 cigarettes; distribution of free samples of cigarettes; distribution of free samples of smokeless tobacco; gifts or other items in exchange for buying cigarettes; sale or distribution of items with tobacco logos; and tobacco brand name sponsorship of any athletic, musical or other social or cultural events.  The rule goes into effect on June 22, 2010.

The final rule finalizes many provisions of a proposed rule the agency issued in 1996 under the leadership of then-commissioner David Kessler.  Among other things, that proposed rule included restrictions on the outdoor advertising of cigarettes and smokeless tobacco “including billboards, posters, or placards, may be placed within 1,000 feet of the perimeter of any public playground or playground area in a public park (e.g., a public park with equipment such as swings and seesaws, baseball diamonds, or basketball courts), elementary school, or secondary school.”  However, the U.S. Supreme Court invalidated the entire rule when it held that the agency did not have the authority to regulate “tobacco products” (cigarettes and smokeless tobacco) in Food and Drug Administration v. Brown & Williamson Tobacco Corp. et. al., 529 U.S. 120, 161 (2000).   Congress granted FDA that authority last year in the Family Smoking Prevention and Tobacco Control Act.  The act explicitly ordered FDA to re-issue the 1996 rule, but directed FDA to “include such modifications to [the section on outdoor advertising restrictions], if any, that the Secretary determines are appropriate in light of governing First Amendment case law, including the decision of the Supreme Court of the United States in Lorillard Tobacco Co. v. Reilly (533 U.S. 525 (2001)).”   In Lorillard, the U.S. Supreme Court struck down Massachusetts's ban on cigarette advertising within 1,000 feet of a school. 

Accordingly, FDA's Final Rule that it published today does not implement the outdoor advertising restrictions of the 1996 rule.  Instead, FDA is requesting comment in a separate Federal Register notice on how FDA might want to implement that part of the 1996 rule.  According to that request for comments, the agency is considering several options, including a regulation proposing to (1) Prohibit or otherwise limit billboards located within 1,000 feet of any elementary or secondary school (k-12) and (2) prohibit or otherwise limit large signs or collections of advertisements greater than 14 square feet at retail establishments located in close proximity to any elementary or secondary school (e.g., within 350 feet or approximately one city block).  FDA also announced that it is seeking data, research, information, and comments related to several questions, including the following:

• Would narrower restrictions on advertising, such as permitting some size greater than 14 square feet at retail establishments located within 350 feet of an elementary or secondary school, still achieve the public health goal?

• Or would a broader prohibition be necessary?  For example, by prohibiting outdoor advertisements in addition to billboards, or by prohibiting small notices on store windows?

• Should FDA require stores that sell tobacco products to post graphic anti-tobacco messages in order to counter the effects of advertisements on children?

As we have reported earlier, a Federal District Court has already invalidated part of the Family Smoking Prevention and Tobacco Control Act on First Amendment grounds, although FDA is appealing that decision.  FDA has recently grappled with First Amendment concerns in other areas too, such as the promotion of off-label indications of drugs, and advertising the services of pharmacy compounders.  FDA’s request for comment on outdoor advertising restrictions of cigarettes is yet another reminder that the agency must consider carefully the First Amendment as it attempts to exercise its authority under the Federal Food, Drug, and Cosmetic Act.

By Kurt R. Karst & Dara Katcher Levy –      

Last week, FDA issued Warning Letters (here and here) to Glenmark Generics (“Glenmark”) and Konec Inc. (“Konec”) for marketed unapproved and misbranded 0.3 mg, 0.4 mg, and 0.6 mg nitroglycerin sublingual tablets.  According to the letters, the companies are in violation of FDC Act § 301(d) and § 505(a) Act because the products are “new drugs” and do not have FDA-approved applications, and the products are misbranded under section FDC Act § 502(f)(1) because “their labeling fails to bear adequate directions for their intended uses.”  The Warning Letters are notable for their reliance on Drug Listing information.

FDA, through the Warning Letters, expects that Glenmark and Konec will cease manufacturing their unapproved nitroglycerin products within 90 days and cease shipping the tablets within 180 days; however, the companies are not required to recall product currently on the market.  Glenmark and Konec have 15 days to respond to FDA with discontinuation plans for the products.  FDA also addressed the issue of the supply of nitroglycerin sublingual tablets in its Q&A, published for consumers of nitroglycerin sublingual tablets. 

Notably, the Warning Letters come from Deb Autor, Director of the Office of Compliance, and cite to drug listing submissions as the basis for the information contained in the letter.  Although Drug Listing information has previously been cited in Warning Letters, it was typically done as an adjunct to cGMP observations resulting from a facility inspection conducted by a District Office. 
 
The electronic drug registration and listing system appears to be giving the Office of Compliance a new mechanism to quickly sort drug listings that appear to be unassociated with any OTC monograph or approved application.  As FDA ramps up its Unapproved Drugs Initiative and as more companies update or initiate drug listings through the electronic system, we can expect to see more Warning Letters directly from the Office of Compliance based solely on drug listing information.

By John A. Gilbert –

The UN Commission on Narcotic Drugs (“CND”) held its 53rd meeting last week in Vienna, Austria. This meeting routinely coincides with the publication of the International Narcotics Control Board’s (“INCB’s”) annual report.  The INCB report provides an annual summary of the status of compliance with the international drug control treaties.  Highlights of the 2009 INCB report include concerns about the increase in prescription drug abuse, especially in the United States, and that increased consumption of narcotic drugs may be a source of increased diversion. The INCB also stated that diversion of precursor substances used in the illicit manufacture of controlled drugs had also increased and noted that among legitimate drugs, stimulants, benzodiazepines and buprenorphine were substances most often reported diverted and abused. The Board singled out buprenorphine for an expanded discussion of reports of abuse and requested countries to reexamine whether current control measures were adequate to prevent diversion and abuse of this drug.  The Board also expressed continued concern over the abuse of drugs in committing sexual assaults.

At the CND meeting discussions centered on ways to improve compliance by all member states in reducing demand and supply of illicit drugs and ongoing concerns about abuse of precursor drugs such as phenylacetic acid.  The CND adopted a resolution to move phenylacetic acid from Table II to Table I of the 1988 Convention thereby requiring additional licensing, recordkeeping and reporting requirements for use of this chemical.  Phenylacetic acid has been increasing reported as being used in the illicit manufacturing of methamphetamine.  

The CND considered numerous resolutions to strengthen drug control.  An important resolution adopted by the CND involved "Promoting adequate availability of internationally controlled licit drugs for medical and scientific purposes while preventing their diversion and abuse."  The resolution was drafted by the United States and calls for countries, the INCB and WHO to ensure adequate availability of opiates for medical and scientific purposes, while working towards reducing the potential for diversion. The resolution also calls on the INCB to report on the progress of these efforts in its 2010 annual report and for the CND to consider this as an agenda item at its 54th meeting in March 2011.

The adoption of this resolution is a welcome recognition by the INCB and the CND of the continued problem of ensuring adequate supply of pain medicine in many parts of the world and the importance of considering the impact on medical availability in drug control decisions.  

By John R. Fleder –

We earlier reported that the United States Sentencing Commission issued an interesting Federal Register notice on January 21, 2010.  We reported that the Commission has proposed to amend the Sentencing Guidelines to require companies to make restitution to identifiable victims, and take other remedial steps including self reporting the violation to the government, as soon as the company learns that it has engaged in criminal conduct.  Of course, any “prohibited act” violation of the FDC Act could be deemed to be criminal conduct under the Park doctrine.  For companies regulated by FDA, this would presumably mean that they would be expected to undertake those actions as soon as they learn through their own audits, and/or receiving an FDA Form 483 that establishes in the company’s view, that a violation of the FDC Act has occurred.  In other words, the Commission would be setting forth the federal government’s position that companies should undertake these actions whether or not they are ever prosecuted or convicted for violating the FDC Act.

On March 17, 2010, Hyman, Phelps & McNamara, P.C. submitted a letter to the Sentencing Commission setting forth our firm’s concerns about this proposed amendment.  The Commission’s January Notice states that comments can be submitted to the Commission on or before March 22, 2010.

By Kurt R. Karst –      

It has been quite a wild ride since a 3-judge panel of the D.C. Circuit issued its March 2, 2010 opinion ruling that FDA’s interpretation of the 180-day exclusivity forfeiture provision at FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC) fails at Chevron step one and that the patent delisting counterclaim provision at FDC Act § 505(j)(5)(C)(ii)(I) added by the 2003 Medicare Modernization Act (“MMA”) must be read together with the patent delisting forfeiture provision at FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), 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.”  The D.C. Circuit’s decision reversed a decision from the U.S. District Court for the District of Columbia.  The case, which concerns the availability of 180-day exclusivity for generic versions of Merck & Co., Inc.’s (“Merck’s”) COZAAR (losartan potassium) Tablets and HYZAAR (hydrochlorothiazide; losartan potassium) Tablets, was remanded to the district court for further proceedings “as the court has yet to address the appropriateness of each form of relief that Teva has sought. . . .”  Teva’s Complaint requested declaratory and injunctive relief.  

Shortly after the March 2, 2010 decision was issued, Teva filed an Emergency Motion To Issue Mandate Forthwith, because althought FDA ordinarily has 45 days within which to seek rehearing, the earliest date that the D.C. Circuit’s mandate could be issued under that order (i.e., April 23, 2010 in this case) would be 17 days after the anticipated April 6, 2010 approval deadline for ANDAs for generic COZAAR/HYZAAR.  FDA’s opposition brief threw a new issue into the mix: did Teva forfeit 180-day exclusivity under FDC Act § 505(j)(5)(D)(i)(VI) because the only exclusivity-qualifying patent – U.S. Patent No. 5,608,075 (“the ‘075 patent”), which was previously identified in the Orange Book as expiring in March 2014 – “expired” in March 2009 after Merck had ceased paying certain patent “maintenance fees”?  (In conjunction with its brief, FDA also established a public docket (Docket No. FDA-2010-N-0134) requesting public comment (here and here) on the issue.)  FDC Act § 505(j)(5)(D)(i)(VI) states that 180-day exclusivity eligibility is forfeited if “[a]ll of the patents as to which the applicant submitted a certification qualifying it for the 180-day exclusivity period have expired.”  Teva, characterizing this new issue as a “thirteenth-hour attempt” to deprive Teva of the benefit of the D.C. Circuit’s decision, vigorously argued in its reply brief that the court should reject FDA’s new argument. 

The D.C. Circuit promptly granted Teva’s motion to issue the mandate (but noting that “the mandate would be recalled if rehearing en banc were granted”).  And in doing so, the court stated that its decision was based “[u]pon consideration of appellant Teva Pharmaceutical’s emergency motion to issue the mandate forthwith, and the opposition thereto.”  That is, the court considered Teva's arguments in the company's reply brief and rejected FDA’s new patent expiration forfeiture theory. 

Now back to the district court, where Judge Rosemary M. Collyer granted Teva’s request for an expedited status conference (which was held on March 15, 2010) and was asked to consider a renewed motion by Apotex to intervene in the case. . . .

On March 16, 2010, Judge Collyer issued an Order declaring that Teva has not forfeited its right to 180-day marketing exclusivity, and ordering FDA not to approve ANDAs for certain strengths of generic COZAAR and HYZAAR until the expiration of Teva’s 180-day exclusivity.  Judge Collyer also granted Apotex’s renewed motion to intervene in the case. 

This case is not likely over yet.  FDA or Apotex could appeal the decision.  Stay tuned . . . .

By Kurt R. Karst –      

In a March 16, 2010 opinion and order, Judge Claude M. Hilton of the U.S. District Court for the Eastern District of Virginia (Alexandria Division) vacated the Patent and Trademark Office’s (“PTO’s”) denial of 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), and remanded the case to the PTO “for reconsideration as to the date of approval under [35 U.S.C. § 156] and to take such actions as necessary to ensure that the ‘404 patent does not expire pending further resolution of these proceedings.”  The question of the availability of a PTE for the ‘404 patent has been going on for many years, and has involved all three branches of government.  The ‘404 patent is scheduled to expire on March 23, 2010, and is subject to a 6-month period of pediatric exclusivity.

FDA approved ANGIOMAX at 5:18 PM on Friday, December 15, 2000 under New Drug Application (“NDA”) No. 20-873, and MDCO submitted its PTE application to the PTO on February 14, 2001 – 62 days after NDA approval (including the December 15, 2000 date of approval).  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).  Under 35 U.S.C. § 156(g)(1)(B)(ii), for purposes of calculating the PTE “regulatory review period,” the approval phase begins on the date the NDA application was initially submitted under FDC Act § 505 for the approved product and ends “on the date such application was approved under such section.”

Judge Hilton’s decision stems from a January 2010 Complaint and Motion for Summary Judgment following the PTO’s January 8, 2010 denial of MDCO’s December 2009 Request for Reconsideration asking 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). 

MDCO’s Complaint alleges that the PTO’s denial of the company’s PTE application for the ‘404 patent and FDA’s decision regarding PTE application timeliness violated the Administrative Procedure Act (5 U.S.C. § 706(2)(A)).  Among other things, MDCO argues that there is a discrepancy in how FDA (and the PTO) treats the dates of NDA receipt and approval:

[U]nder the government’s approach to [the PTE] statute, an application for approval of a new drug received by the FDA after business hours is deemed to be filed on the following business day.  By contrast, when a [NDA] is approved after business hours, the government deems the approval to have occurred on the same business day and takes the position that this day starts the 60-day period for filing a patent term extension application.  Despite this inconsistency, the PTO somehow concluded that its interpretation was mandated by statute and regulation.

As a result, MDCO alleges that “[t]he PTO’s decision is not merely arbitrary and capricious; it is profoundly unfair and undermines the remedial design of the patent term restoration system.” 

In his 18-page decision, Judge Hilton included a litany of reasons that the PTO’s PTE denial was supposedly deficient:

• There is a strong presumption that when Congress repeats the same word in the same statute, it intends for that word to be given the same meaning. In this case, the PTO and the FDA interpreted the word date to have two different meanings in the very same provision, and the PTO offered no explanation for that inconsistency.  The PTO also misperceived the scope of its authority.  The PTO believed that it was precluded from adopting a business hours interpretation of the word date in § 156(d)(1).  But, neither the statutory text nor any other authority forecloses that reading. While the PTO believed that the term date can only be construed to mean calendar day, the statute cannot be so inflexible because the FDA interprets the same word in the same section to mean business day.

• The PTO incorrectly thought a business hours interpretation was foreclosed and did not consider central arguments MDCO advanced, and gave no reason for rejecting them.

• The PTO erroneously believed that it was compelled to follow the FDA's interpretation of the provision of § 156(g)(1)(B)(ii) marking the end of the regulatory review period.  The agency also incorrectly believed that a business hours interpretation of § 156(d)(1) was foreclosed by the plain text of the statute, Federal Circuit precedent, and its own regulations.  Because it believed its hands were tied, the PTO never even considered whether it should exercise its discretion to adopt a "business hours" rule.  Indeed, the PTO must have believed it had no option but to construe the statute as it did: Had the PTO recognized any statutory ambiguity, it should have addressed in its decision the issues raised by MDCO.

• The PTO also incorrectly concluded that Unimed. Inc. v. Quigg, 888 F.2d 826 (Fed. Cir. 1989), controlled this case. Unimed never addressed the question presented here. . . . A few sentences in Unimed could be read to suggest that the date that starts the 60-day period in § 156(d)(1) is the date stamped on the FDA approval letter. But the question at issue here – the proper treatment of an after hours letter – was not presented in Unimed because the extension application at issue there was filed "more than a year after the FDA's final approval letter."

• The PTO's decision was also flawed because the Office erroneously concluded that a next business day rule would be contrary to regulations.

• Finally, the PTO incorrectly believed that in interpreting § 156(d)(1), it was bound to follow the FDA's interpretation of § 156(g)(1)(B)(ii).  Although the PTO asserted that it was independently interpreting § 156{d)(1) and relying on the FDA only to provide it with facts regarding the drug approval process, the PTO effectively determined that the 60-day period under § 156(d)(1) must necessarily start to run whenever the FDA determined that the regulatory review period under § 156(g)(1)(B)(ii) ends.  Consistent with the FDA's interpretation, the PTO concluded that the date stamped in a NDA approval letter is the appropriate trigger for section 156(d)(1).  The PTO's position, however, ignores material differences between § 156(d)(1) and § 156(g)(1)(B)(ii).  The relevant statutory language is different. Section 156(d)(1) calls for the PTO to determine when the product received permission, while § 156(g)(1)(B)(ii) calls for the FDA to determine when the new drug application was approved.  Congress's use of different words suggests that the two terms do not necessarily have the same meaning. . . .   Moreover, the two provisions serve distinct purposes.

Judge Hilton remanded the case to the PTO for reconsideration and directed the PTO to take steps to ensure that the ‘404 patent does not expire pending further resolution of the PTE litigation.  Unless the case is resolved before expiration of the ‘404 patent next week (which seems unlikely), the PTO will probably issue an interim PTE.  35 U.S.C. §  156(e)(1) provides for a PTE to compensate for delays in FDA regulatory review of an NDA, and 35 U.S.C. § 156(e)(2) provides for an interim PTE if the patent “would expire before a certificate of extension is issued or denied under paragraph (1).”  Although the Federal Circuit ruled in 2007 in Somerset Pharmaceuticals v. Dudas that an interim PTE is not available when the PTO has already denied a PTE application, Judge Hilton’s decision vacating the PTO’s denial of a PTE for the ‘404 patent should clear the way for an interim PTE. 

By Riëtte van Laack –

For several years, the Consumers Union and the Organic Consumers Association (“Petitioners”) have urged the U.S. Department of Agriculture (“USDA”) to require that personal care products that use the term “organic” in product labeling comply with the requirements of the Organic Foods Production Act of 1990 (“OFPA”) and the USDA National Organic Program (“NOP”) implementing regulations.  USDA has consistently refused to do so on the grounds that the Agency has no authority over the labeling of personal care products that do not claim to meet USDA organic standards, or that do not consist of agricultural ingredients.  The Agency has, however, agreed that a personal care product may carry the USDA organic seal (permitted only on products that are “100% organic” and “organic”), provided that the product meets the applicable NOP standards.  Thus, a personal care product that bears the USDA organic seal must meet NOP standards; however, if the same product is labeled as “organic” but does not carry the USDA seal, then the NOP standards do not apply. 

USDA’s approach has complicated matters because under certain circumstances NOP standards apply and under seemingly similar circumstances NOP standards do not apply.  For a personal care product labeled as “organic,” the presence of the seal is crucial to determining applicability of the NOP standards.  In contrast, a food labeled as “organic” always must comply with the NOP standards, even if it does not carry the USDA organic seal.  In addition, because USDA does not regulate the use of organic claims without the USDA organic seal on personal care products, other independent organizations have stepped in and launched their own organic certification programs.  As a result, a multitude of standards, including the OFPA/NOP standards, exist for personal care products.  Petitioners assert in a recent complaint to the Federal Trade Commission ("FTC") that the presence of these different standards causes confusion in the marketplace and weakens consumers’ confidence in the organic label on foods.  

Petitioners believe that the OFPA, specifically 7 U.S.C. §§ 6501 and 6505, gives USDA the authority to enforce OFPA’s and NOP’s requirements to any personal care product carrying an “organic” claim.  Petitioners do not address USDA’s position that personal care products that are not agricultural products are not covered by the OFPA, or USDA’s assertion that it lacks authority over personal care products that do not claim to meet USDA organic standards.  Instead, Petitioners ask FTC to stop and prevent any further deceptive use of “organic” claims not compliant with the NOP standards.  They assert that organic labeling of personal care products not compliant with the NOP standards constitutes a violation of section 5 of the FTC Act.  Petitioners ask FTC to further investigate organic claims on personal care products, to consider means of working with USDA to prevent the deceptive use of organic claims, and to prohibit the use of non-NOP compliant organic claims on personal care products.

By Kurt R. Karst –      

FDA’s recent response to a 2009 citizen petition filed by Sandoz, Inc. concerning the appropriate certification to certain Orange Book-listed patents for Takeda’s ACTOS (pioglitazone HCI) Tablets and ACTOPLUS MET (pioglitazone HCl; metformin HCI) Tablets can be summed up in two (Latin) words: Caveat Utilitor (That is, let the user beware).  The cautionary note is to companies that plan to submit (or have already submitted) to FDA ANDAs for generic versions of reference listed drug products with old (i.e., pre-August 2003) Orange Book patent listings.

The Sandoz petition requested that FDA refuse to approve any ANDA for a generic version of ACTOS and/or ACTOPLUS MET if the ANDA includes a so-called “section viii statement” (for the omission of certain patent-protected information) with regard to U.S . Patent Nos. 5,965,584 (“the ‘584 patent”) and/or 6,329,404 (“the ‘404 patent”), but does not also include a Paragraph IV certification to the respective patent.  This is referred to as a split certification.  FDA has previously explained that although a Paragraph IV certification and a section viii statement “are not overlapping, and an applicant does not have the option of making a [Paragraph IV] certification . . . in lieu of, or in addition to, a [section viii] statement,” a split certification with respect to the same Orange Book-listed patent may be appropriate in certain instances:

If [] there are listed patents that present both a product and method of use claim, the applicant may file a paragraph IV certification with respect to the product patent or patent claim and a [section viii] statement that the product that is the subject of the application does not involve a patented method of use with respect to the method of use patent or patent claim.

Both the ‘584 and ‘404 patents were initially listed in the Orange Book prior to August 18, 2003 and were flagged with method-of-use claims.  August 18, 2003 is the date on which FDA’s June 2003 regulations implementing the FDC Act’s patent listing provisions went into effect, and when the Agency made a technological leap in identifying Orange Book-listed patents.  As FDA explains in the Sandoz petition response:

[A]t the time [the ‘584 and ‘404 patents] were submitted, FDA’s Orange Book database lacked the technological capacity to display a single patent as claiming more than one aspect of the drug.  At that time, FDA’s practice was to display a patent that had been submitted as claiming both a drug product and a method of use only for the method of use for which it had been submitted.  Thus, FDA's Orange Book lists each patent as claiming only a method of use and provides a use code for each patent to identify the use for which it was submitted by Takeda.  To alert users to the limitations of patent listings for patents submitted before August 2003, and make them aware that the Orange Book may not describe the complete universe of patent claims to which an ANDA applicant must certify, the Orange Book includes a notation that “[p]atents listed prior to August 18, 2003 are flagged with method-of-use claims only as applicable and submitted by the sponsor” and that “[t]hese patents may not be flagged with respect to other claims which may apply. . . .”

Patents submitted to FDA after August 18, 2003 may be identified in the Orange Book as covering the drug product, drug substance, and/or an approved method of use. 

Relying on statements in complaints filed by Takeda in patent infringement litigation against other generic applicants for allegedly infringing the ‘584 and/or ‘404 patents, Sandoz asserted that Takeda characterized both patents as including not only method-of-use claims, but drug product claims as well.  As such, Sandoz took the position that FDA could, of its own accord, flag the ‘584 and ‘404 patents in the Orange Book with drug product claims and require generic applicant to submit a split certification to both patents.   

In the meantime, Takeda notified FDA that when the company first submitted the  ‘584 and ‘404 patents to FDA for Orange Book listing, such patents were characterized as containing both method-of-use and drug product claims.

FDA, once again affirming the Agency’s ministerial role in Orange Book patent listing issues, and citing the Agency’s regulations at 21 C.F.R. § 314.53(f) for interested persons to challenge Orange Book patent listings, ruled that the Agency would not independently consider Sandoz’s assertions that statements in Takeda patent infringement complaints serve as evidence that the ‘584 and ‘404 patents cover both method-of-use and drug product claims.  Instead:

In keeping with our practice of relying solely on the NDA sponsor’s patent declaration describing relevant patent claims in Orange Book-listed patents, FDA will rely on Takeda’s patent declarations submitted to FDA.  We have evaluated our records and confirmed that Takeda’s original patent declaration to FDA for the ‘584 and ‘404 patents stated that the patents included drug product claims and method-of-use claims.

So, FDA granted the Sandoz petition and stated that the Agency would consider ANDAs that do not address the relevant drug product claims in the ‘584 and ‘404 patents to be ineligible for final approval. 

FDA also commented that:

Under the plain language of the statute, the patent certification requirement is not triggered by the publication in the Orange Book of patent information submitted to FDA.  Rather, . . . the statute requires certification where the patent (or patent claim) claims a listed drug, and where the NDA holder is required to submit and has submitted that patent information to FDA.  This obligation to certify attaches regardless of whether that submission is accurately reflected in the Orange Book.  Thus, the pre-2003 technological limitations that prevented our Orange Book listings from reflecting the fact that Takeda submitted the patents as claiming both a drug product and a method of using that drug product do not limit Takeda’s rights to receive patent certifications for the drug product claims in the ‘584 and ‘404 patents. . . .  Nor does the absence of the drug product information in the Orange Book deprive the eligible ANDA applicant with the first paragraph IV certification with respect to the patent of eligibility for a l80-day exclusivity period . . . . [(emphasis added; internal citations omitted)]

Thus, generic applicants that plan to submit, or that have pending at FDA, ANDAs for generic versions of drug products with pre-August 2003 Orange Book-listed patents would be wise to check that the appropriate certification was submitted to FDA, and, if there are questions about the accuracy of a particular patent listing, submit to FDA a 21 C.F.R. § 314.53(f) request.

By Kurt R. Karst –      

Just one day after FDA Commissioner, Dr. Margaret Hamburg, testified last week before the U.S. Senate Committee on Appropriations, Subcommittee on Agriculture, Rural Development, FDA, and Related Agencies on FDA’s Fiscal Year 2011 budget request, which includes new user fees, Representative Maurice Hinchey (D-NY) announced the introduction of H.R. 4816, the FDA Improvement Act of 2010 (“FDAIA”).  FDAIA is a sweeping reform bill that would unravel the Prescription Drug User Fee Act and other similar legislation establishing user fee systems for medical devices and animal drugs.

Alleging that FDA “as an institution remains too closely tied to the pharmaceutical industry,” the bill would amend the FDC Act to add § 743 to prohibit FDA from collecting user fees paid by companies, and instead require that those funds be deposited into the general fund of the U.S. Treasury.  And “to ensure there is no reduction in FDA services as a result of the loss of those fees, [FDAIA] provides mandatory funding levels that would be appropriated by Congress to ensure no services are lost.” 

FDAIA would also terminate any existing and future user fee agreements concerning FDA review and action goals on drugs, devices, animal drugs, or generic animal drugs.  Under proposed FDC Act § 744:

On and after the date of the enactment of [FDAIA] . . .  The Secretary may not enter into agreements with such persons on particular uses of the fees, including agreements on priorities, performance goals, or other commitments . . . . Any such agreement or understanding that was in effect on the day before the date of [FDAIA] is terminated . . . .  The Secretary is relieved of responsibility for meeting any particular goals concerning such review times that were established in such letters.

Instead:

The Secretary of Health and Human Services . . . shall submit to the Committees on Appropriations and Energy and Commerce of the House of Representatives and the Committees on Appropriations and Health, Education, Labor, and Pensions of the Senate a comprehensive review of the drug and device application and amendment process to identify ways to increase efficiency, reduce paperwork, speed analysis, and promote the quickest possible decision process designed to ensure the entry of safe, effective drugs and devices into the marketplace.

In addition to significantly changing the long-established user fee systems, FDAIA would:

• Establish an independent Center for Postmarket Drug, Device and Biologic Safety and Effectiveness as a separate center at the organizational level immediately below the Office of the Commissioner.  The new center would monitor all approved drugs and create standards for drug advertisements (FDAIA § 3); 

• Require all direct-to-consumer advertisements to include a toll-free phone number to allow consumers to report negative side effects of prescription drugs to the FDA, and impose new user fees on drug and device advertisements (FDAIA § 4 & § 9); 

• Amend FDC Act § 521 to add a new subsection, titled “No Effect on Liability Under State Law,” which states: “Nothing in this section shall be construed to modify or otherwise affect any action for damages or the liability of any person under the law of any State.”  The provision would apply to any civil action pending or filed on or after the date of the enactment of FDAIA, and would be retroactive to the enactment of the Medical Device Amendments of 1976, which added FDC Act § 521 (FDAIA § 5);

• Enable FDA to mandate changes to labels of FDA-approved products if a new risk is discovered, require Secretary of Health and Human Services to review and revise FDA’s drug labeling regulations “to improve the clarity and readability of such labeling,” and require FDA to make available information on all clinical trial adverse events (FDAIA § 6 & § 7);

• Require that all FDA advisory panels be composed of qualified experts who do not have any financial ties to companies who have a stake in the topic under discussion (FDAIA § 8); and

• Amend the FDC Act to add § 1101 requiring FDA to promulgate regulations requiring that, before prescribing a drug “the physician inform the patient that the use for which the physician intends to prescribe the drug has not been approved by the Food and Drug Administration” and “the physician obtain from the patient an acknowledgment of such fact and the consent of the patient to use the drug for such use notwithstanding such fact.require doctors to inform their patients when they are prescribing a drug for an unapproved use” (FDAIA § 10).

Although Rep. Hinchey is reportedly working to “actively garner support among his colleagues in the House” for FDAIA, there are currently no co-sponsors listed for the bill on THOMAS.  It has little likelihood of passage.

By Ricardo Carvajal –

During a webinar on immunity claims sponsored by the Food and Drug Law Institute, Richard Cleland, Assistant Director of FTC's Division of Advertising Practices, confirmed that enforcement actions are in the works against probiotic products that make inadequately substantiated claims.  FTC is particularly concerned about any "immunity claim [that] conveys a general or specific health benefit beyond just maintaining one's immune system."  In FTC's view, such claims must be supported by "competent and reliable scientific evidence of a clinically significant enhancement of that benefit."  This is the second time in as many months that an FTC attorney has singled out probiotics for scrutiny in public remarks (see our prior post here).

During the webinar, Bruce Silverglade, Director for Legal Affairs at the Center for Science in the Public Interest (“CSPI”), presented that organization's objections to the use of structure/function claims that it regards as misleading.  In CSPI's view, any immunity claim is an implied disease claim, and CSPI is "encouraging" states and the private bar to act accordingly.  Several class actions have already been pursued against major food manufacturers for immunity and other claims on probiotic products, and San Francisco recently challenged the use of an immunity claim on a popular cereal.