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  • Preemption of State Law Tort Suits Against Medical Device and Drug Manufacturers

    Are state law personal injury suits against drug and device manufacturers preempted by federal regulation of these products?

    This question has been the subject of much litigation since the early 1990s.  The U.S. Supreme Court has issued a string of decisions in this area, with one case pending.  But the preemption waters are likely to remain roiled for some time to come.  A new twist involves combination device-drug or device-biologic products.

    For the complete post, including an overview of preemption law as applied to drugs and medical devices, click here.

    By Jeffrey K. Shapiro

    Petition Challenges FDA’s View on “Qualified Nutrient Content Claims”

    On June 5, 2008, a citizen petition was submitted to FDA requesting that the Agency “initiate rulemaking proceedings addressing the authoritative statement nutrient content claim provisions” of the Federal Food, Drug, and Cosmetic Act (“FDC Act”).  The petition takes issue with FDA’s November 27, 2007 proposal to prohibit nutrient content claims for Eicosapentaenoic acid (“EPA”) and Docosahexaenoic acid (“DHA”).

    A nutrient content claim characterizes the level of a nutrient in a food, e.g., “high,” “more,” or “good source.”  Until the FDA Modernization Act of 1997 (“FDAMA”), foods could carry only nutrient content claims that were authorized by FDA.  Moreover, only nutrients of the type required to be in nutrition labeling were eligible for nutrient content claims.  FDAMA amended the FDC Act to authorize nutrient content claims based on an “authoritative statement” published by “a scientific body of the United States with responsibility for public health protection or research directly relating to human nutrition,” or by the National Academy of Sciences (“NAS”) which “identifies the nutrient level to which the claim refers.”  Notice of the claim must be submitted at least 120 days before its use.  The notified nutrient content claim may be made until FDA issues a regulation prohibiting the claim. 

    Between 2004 and 2006, FDA received three nutrient content claim notifications for the omega-3-fatty acids Alpha-linolenic acid, EPA, and DHA.  All three notifications stated that the claims were based on authoritative statements in a prepublication copy of a report by the NAS Institute of Medicine (“IOM”).   In November 2007, FDA proposed to prohibit the notified nutrient content claims for EPA and DHA.  The Agency concluded that the IOM publication did not identify a “nutrient level” for EPA and DHA within the meaning of the FDCA, and thus the statements cited as authoritative in the notifications did not meet the statutory requirements.

    The newly filed petition challenges FDA’s view that a notified nutrient content claim must be based on an established reference value such as a Dietary Reference Intake or Daily Value.  According to Petitioners, Congress “intended the phrase ‘nutrient level’ to apply in situations when a Daily Value had not been established and to be broad enough to include any appropriate references to nutrient levels.” 

    The petition also argues that FDA’s narrow interpretation of “nutrient level” conflicts with the First Amendment, and that before prohibiting a notified nutrient content claim, FDA must consider the use of disclaimers “to appropriately qualify authoritative statement nutrient content claims.” 

    Considering its limited resources and the fact that notified nutrient content claims have not been a high priority for FDA, a prompt response to this petition does not appear likely.  However, FDA faces a number of the same issues in comments submitted in response to its proposed prohibition of EPA and DHA nutrient content claims.

    By Riëtte van Laack & Ricardo Carvajal

    Categories: Foods

    Going Once . . . Twice . . . Sold – One PTE to the Company from Massachusetts for $65 Million

    On June 23, 2008, Representative William Delahunt (D-MA) introduced, and the U.S. House of Representatives quickly passed by voice vote, H.R. 6344 – the Responsive Government Act of 2008.  The 12-page bill includes several provisions, including the latest iteration of the so-called “Dog Ate My Homework Act,” which is legislation that would permit the U.S. Patent and Trademark Office (“PTO”) to exercise discretion to accept untimely filed Patent Term Extension (“PTE”) applications.  As we previously reported, a similar provision was added to the Patent Reform Act of 2007 (S.1145) by Senator Edward Kennedy (D-MA) in July 2007; however, efforts to get that bill passed have stalled.

    The impetus for the “Dog Ate My Homework Act” is the PTO’s decision to deny an application submitted by Massachusetts-based The Medicines Company for a PTE for U.S. Patent #5,196,404 (“the ‘404 patent”) covering ANGIOMAX (bivalirudin), an anticoagulant drug product FDA first approved on December 15, 2000 for use in conjunction with aspirin in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty.  The Medicines Company submitted a PTE application to the PTO 62 days after FDA approved the company’s ANGIOMAX New Drug Application (“NDA”).  The patent term extension law at 35 U.S.C. § 156(d)(1), requires the submission of a PTE application “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). 

    Section 4 of the Responsive Government Act of 2008 would amend 35 U.S.C. § 156 to add new subsection (i), which states that the PTO Director “may accept an application under this section that is filed not later than three business days after the expiration of the 60-day period provided in subsection (d)(1) if the applicant files a petition, not later than five business days after the expiration of that 60-day period, showing, to the satisfaction of the Director, that the delay in filing the application was unintentional.”  (The 5-day petition period for a PTE application pending before the PTO would begin on the date of enactment of the Responsive Government Act.)  However, there is a cost for unintentional delay.  “In order to effect a [PTE] under section 156(i) of title 35, United States Code, the patent holder shall pay a fee to the United States Treasury . . . .” 

    The fee for The Medicines Company is $65,000,000.  For other patent owners, the fee is determined based on a complex calculation.  Specifically, the bill states that a patent holder shall pay a fee equal to “(i) $65,000,000 with respect to any original application for a [PTE], filed with the [PTO] before the date of the enactment of this Act, for a drug intended for use in humans that is in the anticoagulant class of drugs” (i.e., ANGIOMAX), or “(ii) the amount estimated under subparagraph (B) with respect to any other original application for a [PTE].”  Under proposed subparagraph (B), the PTO and the Under Secretary of Commerce for Intellectual Property must consider a host of factors to calculate a late-filing fee, including “any net increase in direct spending arising from the extension of the patent term,” “any net decrease in revenues arising from such [PTE],” and “any indirect reduction in revenues associated with payment of the fee under this subsection.”  If enacted, proposed § 156(i) would apply to any application – (A) that is made on or after the date of the enactment of this Act; or (B) that, on such date of enactment, is pending before the Director or as to which a decision of the Director is eligible for judicial review.”

    According to the sponsor and co-sponsors of H.R. 6344 (and as evidenced by its quick passage in the House by voice vote), the PTE provisions in the bill have bi-partisan support and are intended to correct “an anomaly in the patent law.”  In discussing the PTE provisions in H.R. 6344, co-sponsor Rep. Donna Christensen (D-VI) stated that the provisions “will make a minor but important amendment to the landmark Hatch-Waxman Act patent act of 1984.  The act of 1984 has done much to make medicine available and more affordable for countless people in this country.  Inadvertently though, in patent term restoration, there is an inflexible deadline provision which has the potential to limit the good that the act can do.”  A copy of the House floor discussion of H.R. 6344 is available here.

    After passage in the House, H.R. 6344 was referred to the Senate Judiciary Committee for consideration. 

    By Kurt R. Karst    

    Categories: Hatch-Waxman

    First DataBank Announces New Settlement in AWP Litigation

    On June 2, 2008, First DataBank, a private publisher of prescription drug prices in the United States, announced a new proposed settlement in a class action suit alleging that the company conspired with a wholesaler to inflate the Average Wholesale Price (“AWP”) for certain prescription drugs. Among other prices, First Data Bank publishes Blue Book AWPs, which are widely used by Medicaid and private health insurers as a benchmark for reimbursement of prescription drugs. Under the terms of the new agreement, First DataBank will be required to adjust its reporting of Blue Book AWP for approximately 1400 National Drug Codes (“NDCs”) to 1.20 times the Wholesale Acquisition Cost (“WAC”) or Direct Price for those NDCs that are on a mark-up basis, and establish a centralized data repository to facilitate reasonable access to First DataBank material describing its drug price reporting practices. In addition, First DataBank agrees to pay $1 million and certain settlement-related expenses and fees.

    On January 23, 2008, the Court issued an order denying approval of a previous proposed settlement, which would have required that First Databank cease publishing AWP data within two years after the Court’s approval of the settlement, as long as no competitor continues publishing similar AWP data. Because AWP is widely used by third-party payers as a drug reimbursement benchmark, the court was concerned that the original settlement had the potential to affect many providers that were not parties in the lawsuit.

    Although the requirement that First DataBank cease publishing AWP was dropped in the new proposed settlement, First DataBank has announced, independent of the litigation, that it will discontinue publishing the Blue Book AWP data field for all drugs no later than two years after the changes noted above are implemented. First Databank also announced that it will apply the same 1.20 mark-up factor to all other NDCs whose Blue Book AWP is set based upon a markup to WAC or Direct Price in excess of 1.20. First DataBank will continue to publish other drug pricing information including WAC, Direct Price, Suggested Wholesale Price, Federal Upper Limits, as well as other clinical drug information.

    The changes to the Blue Book AWP will become effective on or about 90 days after final court approval of the proposed settlement agreement. The proposed settlement agreement will require preliminary approval by the court, notification to the class members, and final approval by the court. Although the settlement does not require the termination of AWP, First DataBank’s decision to do so could result in significant changes in current reimbursement methodologies.

    By Noelle C. Sitthikul

    Categories: Reimbursement

    House Commerce Committee Posts Responses to its Questions on Biogenerics; Not Surprisingly, the Views Run the Gamut

    On April 3, 2008, Representatives Frank Pallone, Jr., (D-NJ), Chairman of the House Energy and Commerce Committee Subcommittee on Health, and Nathan Deal (R-GA), ranking Republican of the Subcommittee on Health, sent a letter to a diverse group of 35 stakeholders, such as AARP, PhRMA, GPhA, and General Motors, soliciting feedback on how to establish a pathway to allow FDA to approve so-called biogenerics.  According to the letter:

    Members of the Subcommittee on Health are committed to [creating a biogenerics pathway] and several have introduced legislation to establish an abbreviated approval process.  We have found it challenging, however, to reach consensus on a single bill that would accomplish this goal.  In order for the Subcommittee to better evaluate the merits, benefits, and costs of a biosimilars bill, we wish to understand more fully the range of perspectives, concerns, and objectives that might be addressed in such a legislative proposal.  We are also interested as to where consensus exists within the biotechnology community and among other stakeholders.

    Earlier this year, Rep. Anna Eshoo (D-CA), who is a member of the Subcommittee on Health, introduced the Pathway for Biosimilars Act (H.R. 5629).  In February 2007, Rep. Henry Waxman (D-CA), who is also a member of the subcommittee, introduced the Access to Life-Saving Medicine Act (H.R. 1038).  Energy and Commerce Committee member Jay Inslee (D-WA) also introduced a bill in April 2007 – the Patient Protection and Innovative Biologic Medicines Act of 2007 (H.R. 1956).  None of these bills have moved very far along in the legislative process.  Although there was speculation earlier this year that Congress might pass legislation before the conclusion of the 110th Congress, that now seems highly unlikely.  Instead, this issue will probably be taken up by the 111th Congress when it convenes in January 2009.  Nevertheless, stakeholder feedback on the Subcommittee on Health letter could help Congress craft a consensus bill.

    The April 2008 Subcommittee on Health letter includes 6 pages of questions divided among several general areas, including science/safety, regulatory/administrative, interchangeability, patents, incentives/exclusivity/investment, and economic impact.  Earlier this week, the Subcommittee on Health announced the availability of the stakeholder responses.  The stakeholder responses provide a wide range of views on the topic of biosimilars.  For example, the Association of American Universities suggests that “the proposed legislation should avoid the unintended consequence of encouraging patent challenges that unnecessarily involve our researchers in patent litigation, diverting institutional resources away from scientific research,” and that “[t]he longer the data exclusivity period, the more likely it is that a university’s patent will expire before FDA approval of the biosimilar, and thus the less reason for [a biogeneric] applicant to challenge the university’s licensed patents.”  Conversely, GPhA “believes that five-year market exclusivity, along with intellectual property and the patent restoration provisions included in the Hatch-Waxman amendments, provides a reasonable balance between innovation and access and should be used for biogenerics.”  Clearly, as Congress moves forward on biogenerics there will be no dearth of debate on the various issues they raise. 

    By Kurt R. Karst

    Categories: Drug Development

    Wyeth Sues FDA & PTO Over Regulatory Review Period Determination for CYDECTIN PTE

    On June 6, 2008, Wyeth Holdings Corporation and its Fort Dodge Animal Health Division (collectively “Wyeth”) filed a complaint in the U.S. District Court for the District of Columbia against FDA and the U.S. Patent and Trademark Office (“PTO”) requesting declaratory and injunctive relief with respect to Wyeth’s request for a Patent Term Extension (“PTE”) for U.S. Patent #4,916,154 (“the ‘154 patent”), which covers the company’s new animal drug CYDECTIN (moxidectin) Pour-On.  FDA first approved CYDECTIN on January 28, 1998 under New Animal Drug Application (“NADA”) #141-099 for the treatment and control of certain internal and external parasites of cattle.  Although Wyeth’s complaint is in the context of a PTE for an animal drug, a court decision could further clarify the PTE regulatory review period timeframes applicable to FDA-regulated products eligible for an extension.  In addition, this appears to be the first instance in which a company has challenged a PTE for a so-called Administrative NADA, a type of application discussed further below. 

    Under 35 U.S.C. § 156(g)(4), as amended by the Generic Animal Drug Patent Term Restoration Act of 1988, certain patents covering animal drugs are eligible for a PTE if patent life was lost during a period when the product was undergoing regulatory review. As with other FDA-regulated products, such as human drugs and medical devices, the “regulatory review period” is composed of a “testing phase” and a “review phase.”  For animal drugs approved under FDC Act § 512, the “testing phase” begins on the earlier of the effective date of an Investigational New Animal Drug (“INAD”) exemption or the date a major health or environmental effects test on the drug was initiated, and ends on the date a NADA is “initially submitted” to FDA under FDC Act § 512(b).  The “review phase” is the period between the initial submission and approval of the NADA.  FDA’s PTE regulations at 21 C.F.R. § 60.22(f) clarify that a marketing application “is initially submitted on the date it contains sufficient information to allow FDA to commence review of the application.” A patent term may be extended for a period of time that is the sum of one-half of the time in the “testing phase,” plus all the time in the “review phase” (minus any of the “regulatory review period” that occurs prior to the patent issuance or during which the applicant did not act with due diligence to obtain approval).   The total (calculated) regulatory review period may not exceed 5 years, and the extended patent term may not exceed 14 years after the date of approval of the NADA.  The current case concerns when NADA #141-099 was “initially submitted” to FDA. 

    Wyeth submitted a marketing application to FDA for CYDECTIN under the Agency’s Phased Data Review Policy and Administrative NADA process.  An Administrative NADA “is a new animal drug application that is submitted after all of the technical sections that fulfill the requirements for the approval of the new animal drug . . . have been reviewed by [the Center for Veterinary Medicine (‘CVM’)] and CVM has issued a technical section complete letter for each of those technical sections.”  In this respect, an Administrative NADA is similar to the statutory “Fast Track” process for human drugs and biologicals and the Modular Premarket Approval Application process for medical devices.  Both of these processes permit a type of rolling submission and review of marketing application sections.  As we previously reported, FDA and the PTO have addressed both processes with respect to PTE issues.  For example, under current FDA “Fast Track” policy and precedent, the Agency has determined that the date a final reviewable unit is submitted to the Agency is the date the PTE review phase begins.  Wyeth reportedly submitted the first technical section to the company’s INAD on August 8, 1995.  On January 13, 1998, after the submission and acceptance of the last technical section, and pursuant to Wyeth’s submission of an Administrative NADA for CYDECTIN, FDA issued an acknowledgement letter for the application.  Sixteen days later, on January 28, 1998, FDA approved NADA #141-099. 

    In March 1998, Wyeth timely submitted an application to the PTO requesting a PTE with respect to the ‘154 patent.  In that application, Wyeth calculated a PTE based on the date the company submitted the first technical section to its INAD (i.e., August 8, 1995).  Using this date, Wyeth calculated a new expiration date of the ‘154 patent of January 28, 2012. (The original expiration date of the ‘154 patent was April 10, 2007.) 

    In September 2006, FDA issued a Federal Register notice stating the Agency’s determination that the date NADA #141-099 was initially submitted to FDA was on January 13, 1998.  In the notice, the Agency also stated that “[i]t is FDA’s position that the approval phase begins when the marketing application is complete.”  In November 2006, Wyeth submitted a request for reconsideration and revision of the regulatory review period, in which the company argued that August 8, 1995 is the controlling date for PTE purposes.  On May 7, 2008, FDA denied Wyeth’s request.  FDA’s letter provides two bases for the Agency’s decision:

    First, for phased review applications, it is FDA’s position that the approval phase for purposes of [PTE] begins when the marketing application is complete, including all technical sections and the CVM complete letters.  This correlates to the “fast track” and “rolling review” of human drug applications in that applications submitted under those programs are not considered initially submitted until all required technical information is addressed and available for FDA decision making to commence. . . . 

    Second, the technical sections of the administrative NADA are submitted for FDA review not to the NADA, but to the INAD.  Regulatory review of the components is conducted under the first investigational phase of the regulatory review period allowing for review of the data at the time most appropriate and productive in the drug development process. . . .

    A few weeks after FDA’s decision, Wyeth filed its complaint.  The complaint alleges that using the August 8, 1995 for purposes of calculating the regulatory review period is consistent with Congress’ intent in passing the PTE provisions at 35 U.S.C. § 156 and with FDA’s PTE regulations at 21 C.F.R. 60.22(f), and that a mere 16-day approval period “is unreasonable.”

    Wyeth’s complaint asks for a declaratory judgment that FDA’s determination of the regulatory review period for CYDECTIN violated the FDC Act and the Agency’s implementing regulations, as well as injunctive relief directing FDA to recalculate the CYDECTIN regulatory review period and directing the PTO to refrain from issuing a certificate of extension for the ‘154 patent until FDA has recalculated the PTE period consistent with the law.

    By Kurt R. Karst    

    Categories: Hatch-Waxman

    Come Work for HP&M — Hosts of FDALawBlog.Net

    Hyman, Phelps & McNamara, P.C., the nation’s largest dedicated food and drug practice, seeks a mid-level associate experienced in drug/biologics development and approval for our D.C. office.  The ideal candidate will have a scientific or medical background and prior regulatory experience in drug/biologics development issues at a law firm, pharma/biotech company, or FDA.  J.D. and strong writing skills are required.  Must be a member of D.C. Bar (or eligible to waive into D.C. Bar).  Compensation commensurate with experience.  Excellent benefits package.

    Email resume to jwasserstein@hpm.com.  For more information about the firm, see www.hpm.com.  HP&M is an equal opportunity employer.

    Categories: Miscellaneous

    German Government Agency Report Draws Attention to the Safety of Energy Drinks

    The German Federal Institute for Risk Assessment (“BfR”) has issued a report that discusses recent human data on potential health risks arising from consumption of energy drinks.  According to the report, the safety concerns expressed by BfR in a prior expert opinion are “substantiated by more recent human data.”  BfR reiterates its recommendation that the packaging of energy drinks should state that “adverse effects cannot be ruled out when larger amounts of these beverages are consumed in conjunction with intensive physical activity or with intake of alcoholic beverages,” and that “beverages of this kind, particularly when consumed in larger amounts, are not recommended for children, pregnant women, lactating women or individuals who are sensitive to caffeine."  Citing risks of spontaneous abortion, premature delivery, and intrauterine growth retardation, BfR advises a reduction in the daily intake of caffeine for pregnant women (from 300 to 200 mg/day).  With respect to children, BfR cites findings indicating that increased excitability, nervousness, or anxiety are observed at a dose of 5 mg/kg of body weight, and that there is little information on the long term effects of caffeine consumption.  Finally, BfR also raises the question of whether individuals with existing health disorders are at increased risk of adverse effects from consumption of energy drinks, and recommends that patients with high blood pressure or heart disease who consume energy drinks do so in moderation.

    As noted by BfR, a number of European and non-European countries have imposed requirements on, or acted to curtail the sale of, energy drinks.  Given the recent transatlantic furor over reports of potential health risks to children reportedly associated with consumption of certain colors, it would not be surprising to see an increased focus in the U.S. on potential health risks to certain subpopulations that may be presented by consumption of energy drinks.  In fact, New Jersey assemblyman Ralph Caputo was reported to be contemplating introducing legislation that would have prohibited the sale to minors of energy drinks containing large doses of caffeine.  For now, Mr. Caputo appears to have opted to tackle fruit hanging a bit closer the ground – marketing to minors of merchandise, including foods and beverages, that links a product to any “controlled dangerous substance or analog” – a clear strike at energy drinks such as CocaineTM and BlowTM.  For the text of the bill, click here.

    By Ricardo Carvajal

    Categories: Foods

    FDA, Bankruptcy, Criminal Prosecution, Forfeitures and GMPs-An Unusual Combination

    In a case involving a highly unusual set of facts for FDA-regulated companies, Leiner Health Products, Inc. (Leiner) is seeking to have a plea agreement approved by a Bankruptcy court.  The case involves violations of Current Good Manufacturing Practices (cGMPs) for over-the-counter drugs.  What also makes this case unusual is that the violation alleged in the case is not an FDC Act violation for selling adulterated or misbranded drugs.  Instead, the government is apparently seeking a plea from Leiner to violations of the Mail Fraud Act under 18 U.S.C. § 1341.  Also unusual is that under the proposed agreement Leiner would not have to pay any criminal fine.  Instead, it would pay a ten million dollar forfeiture. 

    The Motion, proposed Information and Plea Agreement are available here.

    Categories: Enforcement

    Menu labeling could heat up, with a little help from FDA.

    FDA has filed an amicus curiae brief with the Second Circuit Court of Appeals that supports a New York City (“NYC”) law requiring all menu boards and menus in chain restaurants with 15 or more establishments nationally to bear calorie content information for each menu item.  The case is New York State Restaurant Association v. New York City Board of Health, Docket No. 08-1892-cv.  Oral argument in the case is scheduled for mid-June.  The NYC law is one of several similar local laws or proposals in various stages of consideration across the country.  FDA’s support for the NYC law could lend a boost to similar measures elsewhere.

    In its brief, FDA takes the position that the NYC law is not expressly preempted by the Nutrition Labeling and Education Act of 1990 (“NLEA”) because it compels the disclosure of “information that is properly included in required nutrition labeling” and does not constitute a nutrient content claim.  FDA also takes the position that the NYC law does not violate the First Amendment because it compels “an accurate, purely factual disclosure… and addresses a legitimate state interest in preventing or reducing obesity among its citizens by making accurate calorie information available to consumers.” 

    The possibility of having to adapt to a patchwork quilt of local menu labeling requirements may yet prompt support by industry for federal menu labeling legislation. The Menu Education and Labeling (“MEAL”) Act, introduced by Representative Rosa DeLauro in October 2007, would require that menus disclose next to the name of the food the number of calories, grams of saturated fat plus trans fat, and milligrams of sodium contained in a standard serving of the food.  Menu boards would have to disclose the number of calories per serving.  However, the MEAL act, as proposed, would not preempt state or local requirements mandating disclosure of additional nutrition information.

    By Ricardo Carvajal and Diane McColl

    Categories: Foods

    ACCESS Act Reintroduced by Sen. Brownback; Previous Tiered Approval Nomenclature Scrapped and New Immunity Provision Added

    In late May, Senator Sam Brownback (R-KS) introduced S. 3046 – the “Access, Compassion, Care, and Ethics for Seriously Ill Patients Act” (the “ACCESS Act”).  The bill, which is similar to legislation Sen. Brownback introduced in the 109th Congress with the same title (i.e., S. 1956), is intended to increase terminally ill patients’ access to investigational therapies (i.e., drugs, biological products, and medical devices) prior to FDA approval or clearance, and is one component of the ongoing debate over patient access to investigational therapies.  In December 2006, FDA announced the issuance of proposed regulations to amend and clarify the Agency’s current treatment IND regulations on access to investigational new drugs and to add new types of expanded access for treatment use, as well as a proposal to amend the Agency’s regulations on charging for investigational products.  FDA has not yet issued final regulations with respect to either proposal.  Also, on August 7, 2007, the U.S. Court of Appeals for the District of Columbia Circuit held in Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach in an 8-2 opinion “that there is no fundamental right ‘deeply rooted in this Nation’s history and tradition’ of access to experimental drugs for the terminally ill.”  The decision was appealed; however, earlier this year, the Supreme Court declined to hear the appeal, thereby letting the appellate court decision stand.

    The previous version of the ACCESS Act introduced in November 2005 would have amended the FDC Act to create a three-tier approval system, similar to that advocated by the Abigail Alliance, for products for serious or life-threatening diseases or conditions.  Under that proposed bill, Tier I and Tier II approvals would be conditional approvals based on either clinical evaluation and not statistical analyses (Tier I) or information showing that the investigational product has an effect on a clinical or a surrogate endpoint (Tier II).  Tier III approval would be full approval. 

    The new version of the ACCESS Act scraps the tiered approval nomenclature and replaces Tiers I , II, and III with “Compassionate Investigational Access,” “Accelerated Approval,” and “Final Approval” levels, respectively.  Sen. Brownback explained when announcing the new ACCESS Act that:

    terminally ill patients who have exhausted all available treatment options would have access to treatments currently undergoing FDA approval.  On the Compassionate Investigational Access level, terminally ill patients whose medical needs are unmet by currently available options would be granted access to promising, investigational treatments that have shown evidence that the treatment may be effective against a serious illness considering the risk to the patient from the disease.  On the Accelerated Approval level, ACCESS Act improves the existing system, which allows patients with life-threatening diseases access to treatments that have shown effectiveness upon completion of Phase II clinical trials.  The ACCESS Act also establishes a five-year demonstration program that would offer Medicare coverage for drugs that receive Compassionate Investigational Access approval and makes a technical correction that will increase patient access to drugs used off-label to treat life-threatening diseases.

    In contrast to the previous version of the ACCESS Act, which would have made inapplicable to Tier I and Tier II approvals the FDC Act provisions concerning user fees, Hatch-Waxman benefits, and generic drug competition, the new version of the bill does not include similar provisions.  Also, the new bill includes an immunity provision that would make a manufacturer, distributor, sponsor, or physician who manufactures, supplies, distributes or prescribes a product under a Compassionate Investigational Access application immune from suit or liability with respect to the product.

    A companion bill to S. 3046 will be introduced in the House of Representatives by Representative Dianne Watson (D-CA).  Given the short amount of time left in the 110th Congress, it seems unlikely that Congress will move forward with the new ACCESS Act this session.

    By Kurt Karst

    Categories: Uncategorized

    FDA Proposes New Requirements for Pregnancy and Lactation Labeling

    On May 28, 2008, FDA announced the issuance of a proposed rule to amend the Agency’s regulations concerning the format and content of the “Pregnancy,” “Labor and Delivery,” and “Nursing Mothers” labeling subsections of the “Use in Specific Populations” labeling section for human prescription drug and biological products.  Although FDA substantially revised its labeling format and content regulations in January 2006 to provide, among other things, prescribing information highlights and a table of contents for the full prescribing information, the final regulations did not substantively revise the labeling subsections on pregnancy, labor and delivery, and nursing mothers, but rather moved these sections from the “Precautions” labeling section to the “Use in Specific Populations” labeling section.   (Additional information on FDA’s January 2006 final rule, which is also referred to as the “Physician Labeling Rule,” is available here.)

    FDA’s proposal, which is “intended to create a consistent format for providing information about the effects of a drug on pregnancy and lactation,” would, if finalized: (1) require that prescription drug labeling include a summary of the risks of using a drug during pregnancy and lactation (as well as a discussion of the data supporting that summary); (2) require that prescription drug labeling include “relevant clinical information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and/or lactation;” (3) eliminate the current A, B, C, D, and X pregnancy categories because they have been “criticized as being confusing and overly simplistic;” and (4) eliminate the “Labor and Delivery” labeling subsection, because such information is included in a new “Pregnancy” labeling subsection.

    Under FDA’s proposed “Pregnancy” labeling subsection, prescription drug labeling would be required to contain pregnancy exposure registry information (if applicable), a general statement about the background risk of fetal developmental abnormalities, a fetal risk summary, clinical considerations, and a data component.  Under FDA’s proposed “Lactation” labeling subsection, prescription drug labeling would be required to contain information on the drug’s impact on milk production, what is known about the presence of the drug in human milk, the effects on the breast-fed child, a data component, and a “clinical considerations” component “to help health care providers make informed decisions about prescribing drugs for lactating women.”

    FDA issued the proposed rule more than a decade after the Agency first discussed the practical utility, effects, and problems of the pregnancy categories at a Part 15 hearing in September 1997.  In the years after the hearing, FDA developed a model pregnancy labeling format, conducted focus group testing on the model, and in June 1999 presented a concept paper to the Pregnancy Labeling Subcommittee of the Reproductive Health Drugs Advisory Committee.  Based on the advisory committee’s recommendations, FDA further refined the model format and conducted additional focus group testing.  The advisory committee also recommended that FDA revise prescription drug labeling requirements for nursing mothers because of concern that “current labeling on lactation is not informative for a number of reasons, including lack of data and a tendency for clinicians to conclude, based on the current format of the labeling, that they should recommend to their patients that they choose between breast-feeding and taking a drug.”  Thereafter, FDA held an advisory committee meeting in September 2000 to discuss potential revisions. 

    The new content requirements of the proposed rule would apply to all applications required to comply with FDA’s January 2006 Physician Labeling Rule, which went into effect on June 30, 2006.  This includes: (1) prescription drug products for which an application was approved by FDA between June 30, 2001, and June 30, 2006; (2) prescription drug products for which an application was pending on June 30, 2006; and (3) prescription drug products for which an application was or is submitted anytime on or after June 30, 2006.  Below is a copy of the table in FDA’s proposal describing the Agency’s implementation plan.

    Table 1.–Implementation Plan

    Applications Required To Conform to New Pregnancy/Lactation Content Requirements

    Time by Which Labeling with New Pregnancy/Lactation Content Must Be Submitted to FDA for Approval

    New or Pending Applications:

    Applications submitted on or after the effective date of the pregnancy final rule

      Time of submission

    Application pending on the effective date of the pregnancy final rule

    4 years after the effective date of pregnancy final rule or at time of approval,

       whichever is later

    Approved Applications Subject to the Physician Labeling Rule:

    Applications approved any time from June 30, 2001, up to and including June 29, 2002, and from June 30, 2005, up to and including June 29, 2007

    3 years after the effective date of pregnancy final rule

    Applications approved any time from June 30, 2007, up to and including the effective date of the pregnancy final rule

    4 years after the effective date of pregnancy final rule

    Applications approved from June 30, 2002, up to and including June 29, 2005

    5 years after the effective date of pregnancy final rule

    By Kurt R. Karst    

    Categories: Drug Development

    FDA Delays Implementation of FDAAA Reportable Food Registry until 2009

    As we previously reported, the Food and Drug Administration Amendment Act of 2007 (“FDAAA”) mandates that FDA create a Reportable Food Registry (“Registry”).  The purpose of the Registry is to facilitate tracking of problems in the food supply, and to allow a more rapid response to such problems by FDA and the food industry.  Under new FDC Act § 417, a responsible party must report to FDA the occurrence of a “reportable food,” i.e., a “food . . . for which there is a reasonable probability that the use of, or exposure to, such . . . food will cause serious health consequences or death to humans or animals.”  The failure to submit a report is a prohibited act under FDC Act § 301(mm). 

    Although FDAAA requires that FDA create the Registry by Sept. 27, 2008 and that the Agency issue guidance concerning use of the Registry no later than June 27, 2008.  FDAAA § 1005(e), (f), FDA announced on May 27, 2008 that implementation of the Registry will be delayed.    According to the Agency, because “FDA intends to [use] the business enterprise system,” a system that is under development and will not be operational before Spring 2009, implementation of the Registry will be delayed until at least early 2009.  Meanwhile, FDA requests comments concerning the Registry provision in FDAAA.  Specifically FDA asks for comment on:

    1. “What obstacles, if any, . . . responsible parties anticipate in complying with the requirements of [FDC Act § 417]?”
    2. Suggestions concerning ways to “enhance the quality, utility, and clarity of the information to be submitted to the Registry.”
    3. Suggestions for “an efficient and effective method for providing and receiving notifications” about a reportable food.
    4. Whether, in addition to the eleven data elements currently required in a report submitted to FDA, “other information, if any, would be important” in “notifications to the immediate previous source and immediate subsequent recipient of the [reportable] food.”

    The deadline for written comments is August 11, 2008.

    By Riëtte van Laack

    Categories: Foods

    DEA Final Rule Increases the Allowable Number of Patients for Maintenance and Detox

    On May 22, 2008, the Drug Enforcement Administration (“DEA”) issued a final rule to allow every qualified practitioner to offer maintenance or detoxification treatment to 30 patients without obtaining a separate registration regardless of the number of other qualified practitioners within their medical practice.  DEA previously limited group medical practices to 30 patients.  In addition, qualified practitioners can now treat up to 100 patients if they submit a second notification indicating the need and intent to treat the additional patients to Health and Human Services at least a year after submitting their initial notification.

    Prior to passage of the Drug Addiction Treatment Act of 2000 (“DATA”), the Controlled Substances Act (“CSA”) and DEA regulations required practitioners to obtain a separate DEA registration as a Narcotic Treatment Program (“NTP”) to conduct maintenance and detoxification treatment using narcotic drugs.  DATA amended the CSA by establishing waiver authority for practitioners who dispense or prescribe certain narcotic drugs for maintenance or detoxification treatment.  DEA promulgated regulations to permit qualifying physicians to dispense and prescribe schedule III, IV and V narcotic drugs approved by the Food and Drug Administration for maintenance and detoxification for up to 30 patients in their practice without obtaining a second registration as an NTP. 

    The final rule, which takes effect on June 23, 2008, will allow practitioners to treat more patients.  This should improve treatment in areas currently underserved for addiction treatment.

    By John A. Gilbert and Larry K. Houck

    FTC Issues FY 2007 Pharmaceutical Company Settlement Agreements Summary; Agreements Involving Authorized Generics on the Rise

    Title XI (§ 1112) of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (“MMA”) requires pharmaceutical applicants (both brand and generic) to file with the Federal Trade Commission (“FTC”) and the Assistant Attorney General certain agreements executed on or after January 7, 2004.  (Information on the types of agreements that must be filed is provided in the FTC’s “Pharmaceutical Agreement Filing Requirements”.)  Since the enactment of the MMA, the FTC has published summaries of these agreements.  Copies of previous summaries are available here (FY 2004), here (FY 2005), and here (FY 2006).

    On May 21, 2008, the FTC announced the availability of the Commission’s FY 2007 summary.  According to the summary, the FTC received 45 agreements in FY 2007 (the same number as in FY 2006), with the following breakdown in agreement types:

    • Thirty-three of the agreements were final settlements of patent litigation brought by a brand company against a generic company.

    • Nine were interim agreements that occurred during patent litigation between a brand and a generic company, but did not resolve the litigation.

    • One was an agreement between a first-filer generic company and a subsequent generic filer.

    As in FY 2006, a significant number of final settlement agreements filed in FY 2007 reportedly included both compensation to the generic company and a restriction on generic marketing (79% of these agreements involved “first filer” generics eligible for 180-day exclusivity).  However, according to the FTC, unlike the agreements reported on in the Commission’s FY 2006 summary, the agreements filed in FY 2007 concerning restrictions on generic entry “generally did not include some type of side-deal involving elements not directly related to the resolution of the patent dispute between the brand and the generic.  Rather, in most of these agreements the compensation to the generic takes the form of the brand’s agreement not to sponsor or compete with an authorized generic for some period of time.” 

    FTC Chairman William E. Kovacic commented that “[t]his report confirms that settlements with potentially anticompetitive arrangements continue to be prevalent.  The Commission remains committed to ensuring that brand and generic companies do not use such settlements as a way to deny consumers the benefits of competition.” 

    In March 2006, the FTC proposed a study of the competitive effects of authorized generics.  In April 2007, the FTC announced that it was seeking public comment on its proposed information requests to firms in the prescription drug industry.  In December 2007, the FTC announced the issuance of those information requests.  The FTC has not publicly discussed a timeframe for issuing a study report. 

    By Kurt R. Karst    

    Categories: Hatch-Waxman