By Carrie S. Martin & Dara Katcher Levy –

On March 29, 2010, FDA published a proposed rule to amend its direct-to-consumer (“DTC”) regulations to require that prescription drug advertisements present information about side effects and contraindications in a “clear, conspicuous, and neutral manner.”  Current regulations, found in 21 C.F.R. 202.1, require the disclosure of major side effects and contraindications (commonly known as the “major statement”) in either the audio or audio and visual parts of an advertisement and that they be presented in a comparable manner to any statements regarding the drug’s efficacy. 

With the passage of the FDA Amendments Act of 2007 (“FDAAA”), Section 502(n) of the Food and Drug Cosmetic Act (“FDC Act”) now requires that the major statement in television and radio advertisements to consumers be presented in a “clear, conspicuous, and neutral manner.”  The Agency looked to standards set by other agencies for guidance, including the Federal Trade Commission (“FTC”), the Department of Treasury (“DOT”), and the Securities and Exchange Commission (“SEC”).  FDA now proposes to amend Section 202.1(e)(1) to include four criteria as to when a major statement would be considered “clear, conspicuous, and neutral”:

(1)  The information is presented in language that is readily understandable by consumers;

(2)  The audio information is understandable in terms of the volume, articulation, and pacing used;

(3)  The textual information is placed appropriately and is presented on a contrasting background for sufficient duration and in a manner that can be read easily (e.g., in terms of size and style of font); and

(4)  There are no distracting representations, such as statements, text, images, sound, or any combination thereof, that detract from the communication of the major statement.

FDA admits that these guidelines provide “flexibility” for drug sponsors to be creative in how they meet these four criteria.  In addition, the Agency believes that these proposed guidelines are consistent with the draft guidance it issued in May 2009 about the presentation of risk information entitled “Presenting Risk Information in Prescription Drug and Medical Device Promotion” ("Draft Guidance"). 

Unfortunately, both the draft guidance and the proposed regulations fail to clearly articulate what type of language will be clear, conspicuous, and neutral to consumers.  The draft guidance was the first time the "Reasonable Consumer" standard had been proposed as a basis for judging the presentation of risk information in DTC promotion.  The proposed regulations state that information presented must be "readily understandable by consumers."  However, both the draft guidance and the proposed regulations fail to further articulate "who" these consumers are and what education level they might have.  Nor is there any acknowledgment that certain risk information simply cannot be clearly described in supposed "consumer-friendly" language.  Further, the Agency admits that it was not aware of any previous standard of what constitutes "neutral" in the "context of required disclosures" and asks the public for comments specifically addressing this issue.

Written or electronic comments should be submitted by June 28, 2010.  FDA is particularly interested in comments about whether the final rule should require major statements to be presented in both the audio and visual parts of advertisements, as well as comments about the "neutral" standard.  Written comments can be faxed to the Agency (301-827-6870) or sent to the Division of Dockets Management (HFA-305), FDA, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.  Electronic submissions must go through the following website: www.regulations.gov.

By Peter M. Jaensch –

On March 23, 2010, Judge McMahon of the U.S. District Court for the Eastern District of New York issued a memorandum decision in U.S. Smokeless Tobacco Manufacturing Company, LLC, and U.S. Smokeless Tobacco Brands, Inc. v. City of New York denying plaintiffs’ motion for a preliminary injunction blocking New York City’s recently enacted law (codified at N.Y. Admin. Code §§ 17-713-718) restricting the sale of flavored tobacco.

The New York City ordinance makes it “unlawful for any person to sell or offer to sell any flavored tobacco product, except in a tobacco bar.” The ordinance covers “any substance which contains tobacco, including, but not limited to, cigars and chewing tobacco; provided, however, that such term shall not include cigarettes.” A “tobacco bar” under the ordinance is an appropriately-registered bar “that, in the calendar year ending December 31, 2001, generated ten percent or more of its total annual gross income from the on-site sale of tobacco products and the rental of on-site humidors, not including any sales from vending machines.” Plaintiffs asserted that there are fewer than ten such establishments in New York City.

The Plaintiffs, manufacturers and distributors of smokeless tobacco, argued that the city ordinance was preempted by the federal Family Smoking Prevention and Tobacco Control Act (“FSPTCA”), and that they would suffer irreparable harm because enforcement of the ordinance would cause them to lose revenue, brand equity, adult tobacco consumers and market share.

In a lengthy analysis of federal preemption doctrine, the Court rejected Plaintiffs’ argument. The Court found no grounds in the language of the statute to suggest a Congressional intent to preempt local legislation, and in the absence of an actual conflict, there was no basis for implicit preemption. Absent a basis for preemption, Plaintiffs could not show a likelihood of success on the ultimate merits of their case, a necessary showing to obtain a preliminary injunction.

Rather, the Court held that the FSPTCA explicitly preserves the ability of local governments to enact laws with respect to tobacco products that are “in addition to, or more stringent than, [the federal] requirements,” and further that the FSPTCA’s preemption clause “does not apply to [state or local] requirements relating to the sale [or] distribution…of tobacco products.” In finding no conflict between local and federal law, the Court held that “at most, the City Ordinance applies sales restrictions on flavored tobacco products…over and above those imposed by the federal law.”

The decision by the Court seems likely to forecast what we may expect to see before long in a dispositive motion by the Defendant.

By Jeffrey K. Shapiro –

In October 2009, the Department of Health and Human Services Office of Inspector General (“OIG”) issued a report entitled, “Adverse Event Reporting for Medical Devices” (“OIG Report”).  The OIG’s Report has not received the attention it deserves.  The OIG report demonstrates that the current system of medical device adverse event reporting is broken and in dire need of reform.

Under FDA’s medical device reporting (“MDR”) regulation (21 C.F.R. Part 803), manufacturers must report a serious injury or death to which their device has or may have caused or contributed.  Manufacturers also must report a device malfunction that would be likely to cause a serious injury or death if it were to recur.  These MDR report typically must be filed within 30 calendar days, except in cases where remedial action is necessary to prevent an unreasonable risk of substantial harm to the public health.  The latter reports must be filed within 5 working days.

The OIG examined manufacturer reporting from 2003 through 2007 (OIG Report, pp. 9 13).  The OIG found that the number of 30 day reports doubled from 64,784 in 2003 to 140,698 in 2007.  The five-day reports were relatively fewer, declining in the same time period from 432 in 2003 to 54 in 2007 (the OIG could not determine the reason for the decline).

The OIG took a careful look at how FDA used this data, and reached a startling conclusion.  The OIG found that FDA: “does not use adverse event reports in a systematic manner to detect and address safety concerns about medical devices.” (OIG Report, p. 13)  There was no qualification or mitigation offered to soften this conclusion.  Simply put, the OIG found that between 2003 and 2007, FDA did not make use of the MDR data to improve device safety.

As the OIG notes, the MDR regulation is intended to enable FDA “to take corrective action on problem devices and to prevent injury and death by alerting the public when potentially hazardous devices are discovered” and “to detect unanticipated events and user errors” (OIG Report, p. 1).  Thus, the OIG’s finding essentially means that FDA’s implementation of the MDR regulation failed to meet the basic purpose of the regulation.

Some of the OIG’s subsidiary findings were equally disheartening.  For instance, the OIG found that FDA’s review of MDR reports was generally untimely.  Of the malfunction reports assigned to an FDA analyst for review, the OIG Report found fewer than 1/3 were read within 30 days, and less than half were read within 60 days.  Even the relatively small numbers of 5 day reports were not read in a timely manner.  From 2003 to 2006, FDA analysts read fewer than 1% of these reports within 5 days of receipt.  In 2007, that figure rose to only 6%.  Yet, the 5 day reports are those that likely represent the most serious risk to public health.  These reports can include what FDA calls “Code Blue” reports of pediatric deaths, multiple deaths, exsanguinations, explosion, fire, burns, electrocutions, and anaphylaxis (OIG Report, pp. 15 16.)

The metrics just noted apply only to reports actually assigned to an FDA analyst for review.  Buried within the OIG report is the astonishing fact that FDA “assigns only 10% of malfunction reports to FDA’s analysts for review.”  (OIG Report, p. 15.)  Thus, it appears that FDA routinely does not review 90% of all malfunction reports received each year.

From all this, it is difficult to escape the conclusion that manufacturers have spent billions of dollars over the years to collect, analyze and report adverse event data for little purpose.  Likewise, Congress has appropriated substantial sums of tax dollars for FDA to review, analyze and manage the data without a measurable public health benefit.  The system seems to have operated on autopilot.

For this reason, it may further be said that the MDR reporting system cannot be credited with the substantial improvement in medical device safety that has taken place during the past 26 years.  These improvements have taken place in the absence of meaningful FDA oversight based upon MDR reporting.  One wonders why we needed an expensive system of mandatory reporting to populate a data warehouse that FDA has rarely visited, much less used in the manner envisioned by proponents of mandatory reporting.

The OIG investigation was limited to the period from 2003 to 2007.  It seems unlikely, however, that FDA operated more effectively prior to 2003 or achieved a sudden radical improvement after 2007.  FDA did not publicly dispute the OIG’s findings or suggest that they are already obsolete, even though the OIG Report was not issued until October 2009.

The OIG carefully notes that the conclusion about FDA’s use of adverse event reports rested upon lack of documentation.  So, it is theoretically possible that FDA actually has made effective use of the data.  But there is no evidence that the agency has done so.  Sound public policy is not built on mere speculation and anecdote.  It is FDA’s responsibility to demonstrate that it systematically uses MDR reports to benefit the public health.  According to the OIG, the proof is completely lacking.

It would be a wasted opportunity if the OIG's examination of the problems with the MDR reporting system does not result in useful reform.  There can be no justification for continuing to operate an expensive and time consuming mandatory reporting system on the basis of good intentions rather than actual results.

The OIG does make some recommendations, primarily that FDA should document follow up on adverse events and should ensure and document that CDRH does a better job of meeting its existing guidelines for reviewing 5‑day and Code Blue adverse event reports.  But these recommendations do not get to the heart of the matter.

The most useful immediate reform would be to eliminate the requirement for malfunction reporting.  As the OIG found, FDA analysts have read only a tiny percentage of malfunction reports, so no one can argue that these reports provide essential information that has allowed FDA to systematically address safety problems.  Rather, the evidence is that FDA has not been reviewing most of them in a timely fashion or making systematic use of them to improve device safety.  In addition, because complaints about medical devices can allege all kinds of malfunctions, it is these reports that make up the largest volume of MDR reports that manufacturers must file.  Many of these reports constitute “noise” that, if FDA were actually to analyze them, would obscure more than they illuminate about the safety of medical devices in use today.  Thus, it seems unlikely that malfunction reports could ever be made useful to the agency.

Malfunction reports also create complexities for manufacturers, who must wrestle with determining if a complaint is a malfunction (not all are), and whether a malfunction is reportable because it would be “likely” to cause injury or death if it were to recur.  This latter determination in many cases involves making a difficult and subjective probability prediction.  On the other side of the coin, FDA uses valuable inspectional resources in determining whether malfunction MDRs should have been submitted.  There is something peculiar about a system in which FDA spends compliance resources to inspect files for non-submission of malfunction MDRs which are then submitted, at great cost and effort, and not used by FDA in any meaningful or systematic fashion.

Thus, malfunction reports have generated much of the expensive and complexity of the current system, but have provided little or no benefit.  By contrast, an MDR reporting system that focused on the possible contribution of devices to actual serious injuries or deaths would be easier for FDA to administer, and would more reliably alert FDA to true safety problems.  The smaller resulting data set might also improve the odds that FDA could actually review all of the reports it receives in a timely manner and take action when appropriate. 

In theory it might have been a good idea for FDA to be given malfunction information to help it anticipate device safety problems. But in reality there is no evidence that the system actually operates according to this theory, and the OIG Report provides substantial evidence that it does not. Those who would defend the current malfunction reporting requirement bear the burden of proving that these reports can actually be used to improve medical device safety. If they cannot meet this burden, it is time to try a new approach.

By Riëtte van Laack –

On March 25, 2010, the Food Safety and Inspection Service (“FSIS”) of the USDA published a proposed rule requiring poultry and meat establishments subject to FSIS inspection to promptly notify the authorities when an adulterated or misbranded meat or poultry product has “entered commerce.”

The proposed rule implements certain provisions of the Food, Conservation, and Energy Act of 2008, also known as the 2008 Farm Bill.  The Act amends the Federal Meat Inspection Act (“FMIA”) and the Poultry Products Inspection Act (PPIA) to include a requirement that inspected establishments that “believe or have reason to believe, that an adulterated or misbranded [product] received by or originating from the establishment has entered into commerce, to promptly notify [FSIS] of that belief.”  The notification must include information about the type, amount, origin, and designation of the product.  Previously, the law and regulations did not specifically address notification to FSIS.

The proposed regulation requires that FSIS be notified as soon as possible but at the latest within 48 hours of the time that the establishment learns that an adulterated or misbranded product has been received or been released into commerce.  FSIS specifically requests comments whether 48 hrs is an appropriate time frame.

The proposed rule also includes a requirement that any FSIS-inspected meat or poultry establishment prepare a written recall plan that specifies how the establishment determines whether and how to conduct a recall.  This recall plan may be incorporated into the establishment’s Hazard Analysis and Critical Control Points (“HACCP”) plan.  The proposed rule also includes a requirement for written records of annual reviews/reassessments of the establishment’s HACCP plan.

FSIS expects the new regulations to improve recall response time.  Moreover, FSIS believes that a written recall plan will increase recall effectiveness and efficiency.  In addition, documented annual reviews/reassessments of the HACCP plan will help FSIS determine whether an establishment responds to new developments and emerging hazards.

All documentation and records required under the new rule must be made available for inspection.  Comments on the proposed rule are due on or before May 24, 2010.

By Ricardo Carvajal –

Earlier we blogged on the provisions of the Patient Protection and Affordable Care Act (“PPACA”) that most directly affect pharmaceutical and device manufacturers.  The PPACA also contains a number of provisions that will directly and indirectly affect the food industry.  Most notably, § 4205 adds new FDCA § 403(q)(5)(H) to require restaurants and similar retail food establishments with 20 or more locations doing business under the same name and offering for sale substantially the same menu items to disclose on menus and menu boards (1) calorie content for standard menu items, and (2) information on suggested daily caloric intake.  Such establishments must also make available on the premises other nutrition information, such as the amounts of sodium and sugar per serving.  For self-service food and beverages, disclosure of calorie content is required.  Items not listed on menu boards (e.g., condiments), daily specials, temporary menu items, and foods undergoing a market test are exempt from all nutrient disclosure requirements.  For food sold from vending machines operated by a person who owns or operates 20 or more machines, disclosure of calories is required unless the machine permits a prospective purchaser to examine the nutrition facts panel prior to purchase or otherwise provides visible nutrition information at the point of purchase.

FDA is directed to issue a proposed regulation implementing the requirements of section FDCA 403(q)(5)(H) within one year of enactment.  In issuing the regulation, FDA is directed to consider factors such as reasonable variation in serving size, inadvertent human error, and space on menus and menu boards.  Any state requirement for nutrient disclosures of the type required by § 403(q)(5)(H) would be preempted if the state requirement is not identical to the requirements of that section.  However, restaurateurs and vending machine operators with fewer than 20 locations or machines could be subject to non-identical state requirements unless those restaurateurs and operators choose to subject themselves to the requirements of § 403(q)(5)(H).  State requirements regarding warnings about the safety of a food or component of a food (e.g., those required under California’s Proposition 65) would not be preempted.

Other sections of the PPACA ensure that nutrition will remain at the top of the public health agenda for the foreseeable future.  For example:

• Section 2717 directs Secretary of Health and Human Services to develop reporting requirements for use by group health plans and health insurance issuers with respect to benefits and reimbursement structures that implement “wellness and health promotion activities,” including nutrition. 

• Section 4001 directs the President to establish a National Prevention, Health Promotion and Public Health Council that is to provide recommendations to the President and Congress regarding changes in Federal policy to achieve “national  wellness, health promotion, and public health goals, including the reduction of. . . poor nutrition.”

• Section 4201 provides for the award of grants to State agencies and community-based organizations for the conduct of “community preventive health activities” intended in part to reduce chronic disease rates.  Among the activities eligible for funding are “increasing healthy food options” in schools, “creating the infrastructure to support. . . access to nutritious foods,” “developing and promoting programs targeting a variety of age levels to increase access to nutrition,” and “working to highlight healthy options at restaurants and other food venues.”  The effectiveness of these activities is to be evaluated by measuring changes in weight and changes in “proper nutrition.”

• Section 4206 directs the Secretary to fund a pilot program to develop individualized wellness plans that reduce risk factors for preventable conditions.  The plans would target at-risk populations who use community health centers funded under § 330 of the Public Health Service Act.  The plans can include nutritional counseling and dietary supplements that have health claims “approved” by FDA.  This provision could spark a renewed interest in the use and approval of such claims.

These provisions are certain to enliven the debate about what constitutes good nutrition, and how best to help consumers achieve it. 

By Kurt R. Karst –   

Late last Friday, FDA teed up the next battle over 180-day exclusivity for generic versions of Merck & Co., Inc.’s blockbuster drugs COZAAR (losartan potassium) Tablets and HYZAAR (hydrochlorothiazide; losartan potassium) Tablets when the Agency issued its 8-page decision concluding that Teva did not forfeit 180-day exclusivity eligibility under FDC Act § 505(j)(5)(D)(i)(VI).  That provision 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.”  FDA issued its response after soliciting public comment on whether Teva forfeited 180-day exclusivity eligibility 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 ceased paying certain patent “maintenance fees.” 

FDA’s decision follows a decision earlier in the day on March 26th from the U.S. District Court for the District of Columbia in which the court amended a March 16, 2010 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.  The amended order limits the court’s previous order to the failure-to-market forfeiture provision at FDC Act § 505(j)(5)(D)(i)(VI) and notes that FDC Act § 505(j)(5)(D)(i)(VI) “was not raised in [Teva’s] Complaint, and it was not addressed by the Circuit in its March 2 Opinion or its March 12 mandate.”   Teva had opposed FDA’s motion to amend the March 16, 2010 order on the basis that the D.C. Circuit, before the Court issued its March 12th mandate, considered and rejected arguments that 180-day exclusivity eligibility could be forfeited under FDC Act § 505(j)(5)(D)(i)(VI) when a patent “expires” due to a failure to pay maintenance fees.

FDA’s March 26th letter decision is an interesting strategic move by the Agency.  Although FDA states in the first paragraph of its decision “that the expiration of the ‘075 patent does not result in a forfeiture of the first applicant’s eligibility for exclusivity for ANDAs referencing Cozaar and Hyzaar,” the remainder of the decision is a repudiation of that conclusion.  For example, FDA states:

• The Agency’s view is that, if it were writing on a clean slate, it would interpret the statute so that patent expiration for any reason is a patent expiration forfeiture event.  FDA believes that interpretation is most consistent with the plain meaning of the words of the statute and with a workable and appropriate approach to administration of the statute.

• The text of the patent expiration forfeiture event provision does not provide a basis to distinguish between “natural patent expiry” and expiration for some other reason. Section 505(j)(5)(D)(i)(VI) refers broadly to forfeiture when “all of the patents . . . have expired.”  There is no language qualifying the type of expiration the Agency is to consider relevant for forfeiture.  Thus, there is no apparent statutory basis for the Agency to conclude that only some patent expirations result in forfeiture.

• [P]ermitting the first applicant to retain exclusivity as to an expired patent requires FDA to take an action that is not sanctioned by the words of the statute.

• FDA concludes that if it were assessing this issue without reference to the Teva decision, it would find that, under the plain language of the statute, because the ‘075 patent will have expired by the time any ANDA referencing Cozaar or Hyzaar is ready for approval, any first applicant previously eligible for 180-day exclusivity as to the ‘075 patent forfeits that exclusivity.  Moreover, even if the statutory language is considered ambiguous, FDA concludes [sic] loss of exclusivity under these circumstances is most consistent with the statute’s text and goals, and provides the most reasonable way of administering the statute.

The reference to Teva is, of course, the D.C. Circuit’s 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).  Moreover, the Court ruled that there is “no reason to conclude that the [MMA] meant to give the brand manufacturer a right to unilaterally vitiate a generic’s exclusivity.”

Latching on to this statement, FDA simply states in its letter decision that “[t]his reasoning thus appears to preclude a forfeiture of exclusivity on the basis of a patent expiration where the expiration is in the control of the NDA holder.”  Accordingly, “[b]ecause the ‘075 patent expired due to Merck’s failure to pay applicable fees, that expiration, consistent with the Court of Appeals’ reasoning in Teva, is not a grounds for forfeiture of the first applicant’s exclusivity.  Although FDA believes this result is inconsistent with the plain language of the statute . . . it believes it is appropriate to apply the Court of Appeals’ reasoning to the present facts.”  FDA further notes, however, that “[i]n the event the D.C. Circuit reconsiders and revises the decision in Teva, FDA reserves the right to revisit these conclusions regarding 180-day exclusivity for ANDAs referencing Cozaar and Hyzaar.”  (The Solicitor General is reportedly considering seeking rehearing of the Teva decision.)

FDA’s letter decision is clearly a plea for other interested parties to challenge the Agency’s decision.  Apotex, which is a subsequent ANDA applicant that has already been involved in this 180-day exclusivity litigation, will likely sue FDA soon.  And other subsequent ANDA applicants might do the same.  Indeed, Roxane threatened litigation in the company’s response to FDA’s March 11th solicitation.  We will update our loyal FDA Law Blog readers as things develop.

UPDATE:

• On March 30, 2010, Apotex filed a lawsuit against FDA in the U.S. District Court for the District of Columbia seeking a preliminary injunction enjoining FDA from awarding Teva 180-day exclusivity. A copy of Apotex's memorandum of points and authorities in support of its preliminary injunction motion is available here. 

• On March 30, 2010, Roxane filed a lawsuit against FDA in the U.S. District Court for the District of Columbia seeking a preliminary injunction enjoining FDA from awarding Teva 180-day exclusivity.  A copy of Roxane's complaint and memorandum of points and authorities in support of its preliminary injunction motion are available here and here.  

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.