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  • 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

    Court Denies DEA Injunction to Suspend Practitioner’s Registration

    A U.S. District Court recently denied the Drug Enforcement Administration’s (“DEA’s”) attempt to use an injunction to suspend a physician’s DEA registration.  The court noted that the Controlled Substances Act (“CSA”) provides adequate administrative procedures to suspend a DEA registration.  The court also denied the government’s motion for summary judgment, determining that the government’s contention that the physician prescribed outside the course of professional practice juxtaposed against the practitioner’s assertion that he followed accepted pain guidelines, present genuine issues of material fact to be decided at trial.

    On May 12, 2008,  in United States v. Seth Paskon, Judge Carol E. Jackson of the U.S. District Court of the Eastern District of Missouri denied the government’s motions against Seth Paskon, M.D.  The government alleged that Dr. Paskon issued medically unnecessary prescriptions for narcotic medications.  The government’s civil case against the practitioner under the False Claims Act and the CSA seeking restitution to Medicaid, civil penalties and an injunction against future CSA violations, is set for trial in July. 

    Preliminary Injunction

    The government sought injunctive relief directing Dr. Paskon to immediately stop prescribing controlled substances and to surrender his DEA registration.  The court concluded that the government failed to meet the burden of showing why the injunction should be issued before trial.  The government did not cite, and the court did not find, any cases in which a court limited a physician’s registration prior to disposition of the government’s claims.  The court noted that “the CSA provides a comprehensive regime-complete with standards, burdens, and review procedures-pursuant to which DEA may revoke or suspend a physician’s registration.”  The court further found that the government did not explain why it did not rely on the CSA’s administrative process to stop Dr. Paskon’s prescribing and terminate his DEA registration.  In other words, DEA could have immediately suspended Dr. Paskon’s registration under the CSA’s standard and administrative remedies, that is, if his continued registration posed an imminent danger to the public health or safety. 

    Summary Judgment

    The government also sought partial summary judgment in the matter.   The government alleges that Dr. Paskon violated 21 U.S.C. § 842(a)(1), which provides that it is unlawful for any person to distribute or dispense controlled substances in violation of 21 U.S.C. § 829.  Section 829 provides that controlled substances cannot be dispensed without a prescription issued by a practitioner.  For prescriptions to be valid, they must “be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of his professional practice.” 

    Judge Jackson cited examples from cases where defendant physicians had acted outside the bounds of “professional practice.”  The court distinguished those cases from the case against Dr. Paskon.  For example, the court found no evidence that Dr. Paskon, gave inadequate physical examinations, ignored test results, distributed controlled substances away from the office, or demanded cash for prescriptions. 

    The court noted the government provided an expert opinion but lacked evidence from patients and undercover agents to support its contention while Dr. Paskon contended that he followed accepted guidelines, including the World Health Organization’s Pain Ladder, for managing patients with chronic pain.  Finding that the record presents genuine disputes of material fact, the court denied the government’s motion for partial summary judgment. 

    By Larry K. Houck


    Latest FDLI Update Magazine Features Two Articles Written by HPM Attorneys

    The latest issue of the Food and Drug Law Institute’s “Update” magazine features articles written by three Hyman, Phelps & McNamara, P.C. attorneys.  The first article, titled “FDA Moves Against Marketed Unapproved Human Drugs,” was written by Susan J. Matthees and John R. Fleder and discusses recent FDA actions against companies marketing unapproved drugs.  According to the article, the FDA began an enforcement initiative with respect to such drug products in June 2006 to “ensure that all drugs marketed in the United States meet safety, effectiveness, manufacturing, and labeling standards.”  Since FDA began this initiative, FDA has publicly taken action with respect to many marketed unapproved drugs, including carbinoxamine, colchincine for injection, hydrocodone, and guaifenesin. Since this article was published, FDA announced a new enforcement action against Scientific Laboratories for manufacturing and distributing several unapproved drugs.   

    The second article, titled “The Pathway to Market for Your Medical Device: A Primer on Obtaining Information from FDA,” was written by Jeffrey K. Shapiro and provides an overview of ways to obtain advance information from FDA on regulatory issues concerning medical device clearance.  The article provides a helpful overview of the options available for approaching FDA as well as the pros and cons of each option.      

    FDA Sued After Denying Citizen Petition and Approving Generic EFUDEX Cream ANDA; Agency Will Reconsider ANDA Approval

    Valeant Pharmaceuticals International’s (“Valeant’s”) EFUDEX (fluorouracil) Topical Cream, 5%, (also known as 5-FU) is a locally-acting antineoplastic drug product FDA first approved in July 1970 for the topical treatment of multiple actinic or solar keratoses (“AK”).  In 1976, FDA approved the drug for a second indication – for the topical treatment of superficial basal cell carcinomas (“sBCC”) when conventional methods are impractical.  In December 2004, Valeant submitted a citizen petition to FDA requesting that the Agency not approve any Abbreviated New Drug Application (“ANDA”) for a generic version of EFUDEX Cream unless the application contains data from an adequately designed comparative clinical study conducted in sBCC subjects.  Specifically, Valeant argues in the company’s petition that:

    The inadequate treatment of sBCC can lead to serious complications for patients, including the growth of their cancer. In that light, . . . is critical that FDA not make assumptions about whether a proposed generic product will be safe and effective in treating sBCC, based on a showing of comparable efficacy in patients with AK. These two conditions occur at different sites of drug action and exhibit different growth patterns. Comparable absorption of a drug to one site of action does not demonstrate comparable absorption to another, more difficult to reach site of action. Similarly, comparable efficacy in an easier to treat condition does not demonstrate comparable efficacy in a more difficult to treat condition. 

    For these reasons, FDA must not allow onto the market generic versions of EfudexÒ Cream until a demonstration of bioequivalence has been made, at a minimum, in patients with sBCC.

    On April 11, 2008, FDA denied Valeant’s petition and approved Spear Pharmaceuticals, Inc.’s (“Spear’s”) ANDA #77-524 for Fluorouracil  Cream, 5%.  Citing judicial precedent upholding FDA’s authority to determine the appropriate methods to determine bioequivalence, the Agency states in its petition response that “even when clinical trials are needed, it has not been the Agency’s policy to require that bioequivalence be shown in every indication if drug release from the dosage form and appearance at the or sites of activity has been demonstrated.”  Furthermore, FDA concludes that “an AK bioequivalence study is sufficient to establish that the generic topical 5-FU formulation will be available in the epidermis and the upper dermis to act on both AK and sBCC lesions to an extent that is comparable to Efudex Cream.” 

    Two weeks after denying Valeant’s petition and approving Spear’s ANDA, Valeant sued FDA on April 25, 2008 in the U.S. District Court for the Central District of California (Southern Division) for declaratory and injunctive relief pursuant to the Administrative Procedure Act (“APA”).  Specifically, Valeant requests in the company’s complaint that the court declare FDA’s decision to approve ANDA #77-524 unlawful and invalid and order FDA to suspend ANDA approval.  Valeant also seeks a Temporary Restraining Order (“TRO”) compelling FDA to suspend ANDA approval.  (Valiant’s TRO is filed under seal.)  FDA, as the Agency did in its petition response, argues in its TRO opposition memorandum that the Agency has broad discretion to determine the appropriate requirements for a generic applicant to demonstrate bioequivalence.  Furthermore, FDA argues that its petition decision and ANDA approval are entitled to deference under the APA, and that Valeant has not met the requirements to support a TRO.  Spear, which has intervened in the case, makes similar arguments in its TRO opposition papers and also alleges that Valiant’s lawsuit and citizen petition are merely tactics to block or delay generic competition.  (Valiant’s petition was submitted to FDA prior to the enactment of the FDA Amendments Act, which amended the FDC Act to require FDA to take final action on certain petitions that would delay generic drug approval within 180 days after petition submission.)

    After submitting its TRO opposition papers, FDA became aware of an “administrative issue” and “an additional issue concerning Spear’s ANDA which, in the agency’s judgment, necessitates administrative reconsideration of the ANDA approval,” and requested that the court stay proceedings and refer the matter to FDA.  On May 14, 2008, FDA issued an “Administrative Reconsideration and Stay of Action” to Spears staying the approval of ANDA #77-524, and the company has since suspended selling the drug product.  FDA hopes to complete its review of these issues and the administrative reconsideration process by May 30, 2008.  Until then, further litigation is stayed.

    It is unclear what, exactly, the two issues are that led FDA to suspend the approval of ANDA #77-524.  According to FDA’s Orange Book, EFUDEX Cream, 5%, is not subject to any period of patent or non-patent market exclusivity, so the administrative and scientific issues referred to by FDA would not appear to involve such issues.  We will update you as we learn additional information.

    By Kurt R. Karst    


    Categories: Hatch-Waxman

    FDA to Hold Public Meeting on the Evaluation of Trade Names

    FDA recently announced that on June 5 and 6, 2008, the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research will hold a public meeting to discuss the Agency’s plans to launch a pilot program on the testing and review of proprietary names and the issuance of a concept paper that will describe the logistics of the pilot program, recommendations for implementing a proprietary name review, and the proposed review of submissions made under the pilot program.  The pilot program will allow participating companies to submit data generated from their own testing and evaluation of proposed proprietary product names.  FDA expects to issue the concept paper by the end of Fiscal Year (“FY”) 2008 and begin enrollment in the pilot program in FY 2009.

    The pilot program and concept paper are intended to increase the transparency of FDA’s review process of proprietary names and to decrease the risk of medication errors. Currently, FDA reviews proprietary names to determine any promotional or safety issues.  For example, FDA considers whether a proposed name overstates the efficacy of the drug product, minimizes the drug product’s risks, or broadens its indications.  FDA also considers whether the name is spelled similarly or sounds similar to another marketed product or could otherwise cause confusion, such as having similar abbreviations.  The current safety review expands the entire medication process, taking into consideration, for example, errors that could arise during the procurement, prescribing, ordering, dispensing, and administration of a drug.

    Under the performance goals FDA agreed to as part of the recent reauthorization of the Prescription Drug User Fee Act (i.e., PDUFA IV), the Agency committed to implement various measures with respect to proprietary name review in an attempt to reduce medication errors.  These measures include meeting certain proprietary name review performance goals (beginning in FY 2009) during the IND and NDA/BLA review phases, publishing guidance and policy procedures on proprietary name review and best practices, developing and implementing a pilot program “to enable pharmaceutical firms participating in the pilot to evaluate proposed proprietary names and submit the data generated from those evaluations to the FDA for review,” and “exploring the possibility of ‘reserving’ proprietary names for companies once the names have been tentatively accepted by the Agency.”  FDA’s June 2008 meeting is part of the Agency’s efforts to meet these goals.  FDA’s efforts also respond to calls for more industry involvement in the proprietary name testing process, including requests made in reports by the Institute of Medicine in 2006 and 1999 and recommendations made by the Health and Human Services Advisory Committee on Regulatory Reform in November 2002. 

    During the meeting, FDA plans to discuss the following key issues: (1) best practices in safety and promotional testing of proprietary names; (2) testing procedures that should be used and data that should be submitted by those participating in the pilot; (3) standardization of testing; (4) criteria to consider in evaluating the testing and data submitted; (5) the structure and evaluation of the pilot program; and (6) any public health concerns raised by the pilot program.  FDA will use the information gathered from the meeting and from comments submitted to the docket to develop the concept paper and the pilot program.

    The meeting will be held from 8:30 a.m. to 5:00 p.m. each day at the Crowne Plaza Hotel in Silver Spring, Maryland.  Information on meeting attendance and registration is provided in FDA’s Federal Register notice announcing the meeting.  Written comments regarding the concept paper and pilot program must be submitted by July 6, 2008 to the Division of Dockets Management or electronically at www.regulations.gov.

    By Carrie S. Martin

    Categories: Drug Development