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  • FDA Issues Request for Notification of Participation in New DTC User Fee Program

    Earlier today, FDA issued a Federal Register notice explaining the new Direct-to-Consumer (“DTC”) user fee program established by the FDA Amendments Act of 2007 (“FDAAA”) and requesting companies to notify the Agency within 30 calendar days whether they intend to participate in the program during FY 2008 – and if so to identify the number of planned DTC television ads in that period.  The notice, as well as other information, is also available on FDA’s Division of Drug Marketing, Advertising, and Communications (“DDMAC”) DTC user fee website.  FDA’s DTC advertisement user fee Performance Goals are available here (see Section B) and describe the Agency’s phased-in performance metrics through FY 2012.

    The new DTC user fee program, codified at FDC Act § 736A (“Fees Relating to Advisory Review of Prescription-Drug Television Advertising”) is voluntary and authorizes FDA to assess and collect fees for the pre-dissemination review of DTC televisions ads.  Under the new program, FDA will review and provide comments regarding its view of a submitted DTC advertisement’s compliance with the FDC Act, provided that the established user fee has been paid and that the advertisement has not yet been disseminated.  Applicants need not avail themselves of this new system and can instead continue to submit DTC advertisements to FDA in their normal course of business.  Any advertisements for which FDA pre-dissemination review is required are not subject to the user fees authorized by FDC Act § 736A. 

    Although FDAAA established an upper limit of $83,000 per submission for the FY 2008 fee, FDA explains in the notice that:

    The fee will be based on the number of advertisements identified in response to this participation notice. The advisory review fees in FY 2008 will be set at a level to generate target revenues of $6.25 million in the first year of the program. Individual fees will be determined by dividing the target revenue, established in the statute, by the number of proposed television advertisements that all companies have indicated (in response to the participation notice) that they intend to submit during FY 2008.

    The DTC user fees the Agency collects will be used to fund approximately 27 additional DDMAC staff for the Division’s pre-dissemination advisory review. 

    Whether or not the new DTC user fee program will actually be implemented will depend on how many companies commit to the program.  FDAAA provides that the program will not commence if FDA fails to receive at least $11.25 million within 120 days after enactment of FDAAA (i.e., January 25, 2008).

    The DTC user fee program is one of two DTC provisions included in FDAAA.  FDAAA also amended the FDC Act to create § 503B (“Prereview of Television Advertisements”), which gives FDA the authority to require pre-review of television advertisements.  FDA’s authority under this provision is generally limited to providing recommendations after reviewing an ad.  FDA may require a change if it addresses a serious risk with the drug, or if the Agency requires the inclusion of the approval date in the ad (which may occur for up to 2 years after approval).   

    Categories: Drug Development

    When Safe and Effective Means Neither Safe Nor Effective

    We previously reported on a May 2007 Proposed Decision Memorandum issued by the Centers for Medicare and Medicaid Services (“CMS”) that would restrict the use of Erythropoiesis Stimulating Agents (“ESAs”) in cancer-related anemia and similar conditions.  The proposed memorandum was finalized in a July 30, 2007 National Coverage Determination (“NCD”).  The final NCD provides coverage, with restrictions, for treatment of chemotherapy-induced anemia in certain cancer types, such as solid tumors, multiple myeloma, lymphoma, and lymphocytic leukemia. ESAs are FDA-approved to stimulate red blood cell production, thereby preventing the need for blood transfusions.  Had this been the end of the matter, this might have posed an interesting administrative law hypothetical.  Recent inquires and proposed legislation from Congress on the ESA coverage issue, however, have raised interest in the issue.

    On October 2, 2007, Representatives Henry Waxman (D-CA) and Pete Stark (D-CA) sent a letter to FDA asking for the Agency’s view on the NCD.  FDA responded in an October 12, 2007 letter in which the Agency essentially agreed with the CMS decision.  Specifically FDA’s response notes a number of health risks associated with the use of ESAs, including promotion of tumor growth and increased mortality and cardiovascular events.  ESAs are FDA-approved for hemoglobin levels of up to 12 g/dL; however, the July 30, 2007 NCD restricts ESA coverage to when hemoglobin is less than 10 g/dL.  FDA reconciled this difference by noting that the 12 g/dL level in FDA-approved labeling is “an upper safety limit for ESA dosing, not a target for the therapy.”  FDA further explained that ESAs are intended and approved to prevent the use of transfusions in patients with cancer and related diseases.  This is consistent with the CMS decision, because transfusions are rarely given to patients with a hemoglobin level of greater than 10g/dL.  FDA also noted that there was no corresponding higher quality of life in patients whose hemoglobin levels were higher than that needed to avoid blood transfusions. 

    This decision certainly has monetary implications for drug manufacturers, as preliminary estimates on the cost of pending legislation (i.e., House Joint Resolution 54) that would overturn the July 30, 2007 NCD are estimated to cost Medicare $2.1 billion over the next 5 years.  But it also raises interesting questions about labeling.  FDA had previously issued a Black Box warning for ESAs expressing the same concerns about efficacy and advising that “the lowest dose necessary to avoid the need for blood transfusions” be used.  FDA has not, however, changed the 12 g/dL limit in the labeling itself.  This could therefore be considered a liberal interpretation of the requirement that the labeling set forth the conditions for which ESA use would be “safe and effective.”


    The American Society of Clinical Oncology (“ASCO”) and the American Society of Hematology (“ASH”) announced updated ESA Treatment Guidelines.  Among other things, the updated Treatment Guidelines recommend “the use of ESAs as a treatment option for cancer patients who become anemic as a result of chemotherapy when their hemoglobin approaches or falls below 10 g/dL, as well as patients with low-risk myelodysplasia.”  Additional information on the updated ASCO/ASH guidelines is available here and here.

    Categories: Reimbursement

    Mass. Court Permits Pharmacy Mailing Program, But Requires Disclosure of Profits

    Many pharmacies send letters to consumers advising them about refill or alternative products.  Generally, these “refill reminders” are paid for by pharmaceutical manufacturers.  A recent decision, however, will require more specific disclosure about the funding of such letters in the future.  The Superior Court of Massachusetts in Suffolk County recently decided that pharmacies can use a third party to send prescription-related letters to customers, but if they profit from sending the letters, they must disclose that information to recipients. 

    In Kelley v. CVS Pharmacy, the plaintiff, Jeffrey Kelley, used a CVS pharmacy to fill his diabetes drug prescriptions.  In 1997, Mr. Kelley received a letter on CVS stationery from the “Staff of CVS/Pharmacy” explaining to him the detrimental effects of high cholesterol and the benefits of cholesterol-lowering medication, and encouraging him to have his cholesterol checked.  At the very bottom of the letter in small print was the statement “[f]unding for this mailing was provided by Merck & Co. Inc.”  CVS used a third party, Elensys, to send the letters.  Mr. Kelley sued on the basis that the letter violated his right to privacy and that CVS, Elensys, and Merck engaged in an unfair and deceptive act by sending the letters. 

    The court held that the letter did not violate Mr. Kelley’s right to privacy.  In Massachusetts, an invasion of privacy requires an “unreasonable, substantial, or serious interference” with privacy.  In this case, CVS did not disclose Mr. Kelley’s name to Merck, and only provided his name, date of birth, and address (all of which is public information) to Elensys.  Elensys did not know why Mr. Kelley had been selected to receive the letter and did not receive any information about his medical or pharmaceutical history.  The court reasoned that there is nothing improper about a pharmacy reviewing its prescription database and providing relevant information to its customers, and that the fact that CVS used a third party to do this was essentially the same as hiring extra clerks to send the information directly from the pharmacy.  The court also noted that Mr. Kelley “readily disclosed” his diabetes to friends and associates, which made it “even clearer that the information disclosed by CVS cannot reasonably be deemed a substantial or serious interference with his privacy.” 

    The court, however, did find that CVS engaged in an unfair and deceptive act by concealing the fact that it profited from sending the letters.  Merck paid CVS $2 per letter sent, but CVS only paid Elensys 93 cents per letter, with CVS pocketing the difference as profit.  The disclosure at the bottom of the letter did not mention that CVS profited from sending the letters.  The court explained that in order to fully evaluate the medical information in the letter, a patient should know that CVS is making a profit from the letters.  Although CVS could send information to its customers and drug companies could reimburse CVS for the cost of mailing, once CVS began to make a profit from the letters and failed to reveal this to its customers, it became an unfair and deceptive act.  Merck, for whose benefit the letter was sent, was also found liable. 

    We note that the decision is consistent with what we have been hearing for several years from the offices of Attorneys General (most notably that of Florida) concerning similar pharmacy mailing programs.   

    Categories: Drug Development

    Congress Requires Action on FDA’s Proposed Toll-Free Number Adverse Event Reporting Labeling Rule

    Buried in Title V of the recently-enacted FDA Amendments Act ("FDAAA") is a provision requiring FDA, with certain limitations, to either publish final regulations to provide for the addition of a toll-free number to product labeling to report adverse events, or to make the Agency’s proposed regulations effective beginning on January 1, 2008.

    When the Best Pharmaceuticals for Children Act ("BPCA") was enacted in January 2002, Congress required FDA to promulgate regulations to add to product labeling a toll-free number to report adverse events.  Specifically, BPCA § 17(a) states:

    Not later than [January 4, 2003, FDA] shall promulgate a final rule requiring that the labeling of each drug for which an application is approved under [FDC Act § 505] (regardless of the date on which approved) include the toll-free number maintained by [FDA] for the purpose of receiving reports of adverse events regarding drugs and a statement that such number is to be used for reporting purposes only, not to receive medical advice. With respect to the final rule: 

    (1) The rule shall provide for the implementation of such labeling requirement in a manner that the Secretary considers to be most likely to reach the broadest consumer audience. 

    (2) In promulgating the rule, [FDA] shall seek to minimize the cost of the rule on the pharmacy profession. 

    (3) The rule shall take effect not later than 60 days after the date on which the rule is promulgated.

    On April 22, 2004, FDA published proposed regulations in the Federal Register.  In the preamble to FDA’s proposed regulations, the Agency explained that:

    the MedWatch system should be used to fulfill the requirements of the BPCA for providing a toll-free number for the purpose of receiving adverse event reports regarding drug products.  FDA is proposing that the side effects statement be distributed with each prescription drug product, both new prescriptions and refills, approved under [FDC Act § 505] and dispensed to consumers by pharmacies and authorized dispensers in an outpatient setting. FDA is proposing a number of options/alternatives to meet this proposed requirement.  FDA also is proposing to require the side effects statement in two categories of drug product labeling: (1) FDA-approved Medication Guides for drugs approved under [FDC Act § 505], and (2) the labeling for OTC drug products approved under [FDC Act § 505].

    Although FDA received relatively few comments on the proposed rule, the Agency has not yet published final regulations.  According to an October 11, 2007 Federal Register notice and Supporting Statement submitted by FDA, "[a]fter the publication of the proposed rule and based on the comments received, it was decided to delay the issuance of the final rule in order to conduct research to study the wording of the proposed side effects statements."

    Apparently frustrated with FDA’s failure to make sufficient progress to issue final regulations, Congress included the following provisions in FDAAA § 502(f) (Title V reauthorizes the BPCA through Fiscal Year 2012):

    (1) IN GENERAL- Notwithstanding [the Administrative Procedure Act] and any other provision of law, [FDA’s April 22, 2004 proposed rule] shall take effect on January 1, 2008, unless [FDA] issues the final rule before such date.

    (2) LIMITATION- The proposed [or final] rule that takes effect under [BPCA § 17(a) (2002)] shall, notwithstanding [BPCA § 17(a) (2002)], not apply to a drug —

    (A) for which an application is approved under [FDC Act § 505];

    (B) that is not described under [FDC Act § 503(b)(1)]; and

    (C) the packaging of which includes a toll-free number through which consumers can report complaints to the manufacturer or distributor of the drug.

    FDAAA § 502(f)(2) therefore limits the application of FDA’s proposed regulations (if they go into effect in January 2008) or any final regulations issued before January 1, 2008 to exclude OTC drugs approved under a marketing application if certain labeling requirements are met.  The limitation to prescription drugs is presumably intended to clarify Congress’ original intent in BPCA § 17(a).  Indeed, at least one comment submitted in response to FDA’s April 2004 proposed rule noted that OTC drugs were not the intended target of BPCA § 17(a).

    It is unclear at this time whether FDA will be able to meet the January 1, 2008 deadline when the Agency’s proposed regulations are scheduled to go into effect.  Given FDA’s recent activity as noted in the Federal Register, however, the Agency appears to be moving ahead with its plans to finalize the proposed rule. 

    Categories: Drug Development

    Another Food Safety Bill Will Likely Join the Crowd

    Last week we reported on an influx of food safety bills that have been and that are planned for introduction in both the U.S. House of Representatives and the U.S. Senate.  The already crowded field became a little more congested when Representative Rosa DeLauro (D-CT), chairwoman of the House Appropriations Committee, Subcommittee on Agriculture, Rural Development, Food and Drug Administration Appropriations, announced her plans during a speech at George Washington University on FDA’s future to introduce her own bill, the Food Safety Modernization Act (“FSMA”).  A copy of Rep. DeLauro’s speech is available here.

    FSMA appears to be the most ambitious food safety bill planned for introduction, as it would remove FDA’s jurisdiction over foods and create a new federal agency dedicated to regulating foods.  The new agency, dubbed the Food Safety Administration, would fall under the Department of Health and Human Services.  FDA would be renamed the Federal Drug and Device Administration.  The Food Safety Administration would be headed by a newly appointed Commissioner of Food Safety and Nutrition Policy. 

    Rep. DeLauro has long been critical of the current regulatory structure, which places food safety in the hands of 15 different federal agencies.  She hopes that her bill, if enacted, would streamline food regulation, place greater emphasis on food safety, and allow the government to more effectively respond to emerging threats.  Rep. DeLauro currently plans to introduce FSMA in 2008 after several details are worked out; however, given the fact that 2008 is an election year, it seems unlikely that Congress will have the time to carefully consider and pass broad food safety legislation anytime soon.     

    The recently-enacted FDA Amendments Act addresses some food safety issues (both human and pet food).  In particular, Title X of the new law creates a Reportable Food Registry under FDC Act § 417 for foods “for which there is a reasonable probability that the use of, or exposure to, such article of food will cause serious adverse health consequences or death to humans or animals,” and it requires FDA to develop a more efficient and effective system for communicating information during a food recall.  In addition, § 912 of the new law (i.e., “Prohibition against food to which drugs or biological products have been added”) may also create new hurdles for the development of functional food ingredients.

    Categories: Foods

    FDA Solicits Public Comment on Yet Another 180-Day Generic Drug Exclusivity Issue

    For the third time in as many weeks, FDA has requested public comment to help resolve 180-day exclusivity issues.  This time FDA’s request concerns the antinauseant and antiemetic drug granisetron HCl, which is marketed by Roche under the tradename KYTRIL.  In late September, FDA solicited comment on acarbose (PRECOSE) (9/26/2007 FDA Law Blog post) generic exclusivity issues, and earlier this week the Orange Book Blog reported that FDA requested comment on ramipril (ALTACE) 180-day exclusivity issues.  These requests follow others from earlier this year on a variety of exclusivity issues concerning amlodipine besylate and midodrine HCl.

    FDA’s latest solicitation is the result of a letter submitted by Teva Parenteral Medicines (“Teva”) and involves the “failure to market” 180-day exclusivity forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I).  Under these provisions, a generic applicant whose ANDA contains a paragraph IV patent certification and who is a “first applicant” eligible for 180-day exclusivity forfeits eligibility for such exclusivity if the firm fails to market the drug by the later of:

    (aa) the earlier of the date that is —

    (AA) 75 days after the date on which the approval of the application of the first applicant is made effective under subparagraph (B)(iii); or

    (BB) 30 months after the date of submission of the application of the first applicant; or

    (bb) . . . the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv), at least 1 of the following has occurred:

    (AA) In an infringement action brought against that applicant with respect to the patent or in a declaratory judgment action brought by that applicant with respect to the patent, a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed.

    (BB) In an infringement action or a declaratory judgment action described in subitem (AA), a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed.

    (CC) The patent information submitted under [FDC Act § 505(b) or (c)] is withdrawn by the holder of the application approved under [FDC Act § 505(b)].

    These forfeiture provisions, which were added to the FDC Act by the Medicare Modernization Act (“MMA”) in December 2003, have been controversial.  Indeed, Senator Orrin Hatch (R-UT) expressed concern about how to interpret them within 24 hours of the MMA’s enactment.  Teva’s letter to FDA illustrates a current example of the complexity of the statutory forfeiture provisions. 

    In May 2004, Teva submitted the first ANDA to FDA containing a paragraph IV certification for a generic version of KYTRIL.  The application also contained a paragraph III certification (date of patent expiration) and a section viii statement to a method-of-use patent.  Roche did not sue Teva (or any subsequent ANDA applicant) for patent infringement, and FDA tentatively approved Teva’s ANDA in August 2005.  To date, FDA has not approved Teva’s ANDA, and cannot do so until the patent subject to the paragraph III certification expires in December 2007.  Nevertheless, the 30-month period described in FDC Act § 505(j)(5)(D)(i)(I)(aa)(BB) above expired in November 2006. 

    Teva argues that despite the expiration of the 30-month period, the firm remains eligible for 180-day exclusivity, which would be triggered by Teva’s commercial marketing of the drug.  Specifically, Teva’s letter states:

    [T]he plain language and structure of the [FDC Act] compel the conclusion that Teva is entitled to 180-day exclusivity because Teva is the first applicant that submitted a substantially complete paragraph IV ANDA . . . .  Teva’s exclusivity has not been forfeited . . . because there is a continuing possibility of ANDA-based patent litigation that could result in a “later” forfeiture event under [FDC Act § 505(j)(5)(D)(i)(I)]. . . .

    [The FDC Act] requires FDA to determine which is “the later of” (1) a determinate forfeiture trigger . . . “or” (2) a contingent forfeiture trigger . . . .  But there is no conceivable way for FDA to determine which of those 2 potential triggers occurs “later” until (a) one of the contingencies that could give rise to a forfeiture trigger [under FDC Act § FDC Act § 505(j)(5)(D)(i)(I)(bb)] has occurred, or (b) none of the contingencies can occur.  After all, it is impossible to know whether a contingent event has occurred before it does occur — and twice as hard to determine that such an event will not occur until it no longer can occur.

    FDA’s increasing trend to attempt to resolve post-MMA 180-day exclusivity issues on a case-by-case basis, instead of the Agency proactively addressing such issues more broadly in proposed and final regulations, may very well mean that the courts will end up setting the ground rules for interpreting the FDC Act’s exclusivity provisions, even more so than under the pre-MMA exclusivity provisions. 

    Categories: Hatch-Waxman

    HPM Issues Detailed FDAAA Summary and Analysis

    Earlier today, Hyman, Phelps & McNamara, P.C. issued its detailed summary and analysis of the recently-enacted FDA Amendments Act (“FDAAA”).  A copy of the summary and analysis is available here. 

    FDAAA reauthorizes several user fee and pediatric-related laws, and includes a host of new provisions, the longest reaching of which concern drug safety.  FDAAA also creates a new Direct-To-Consumer (“DTC”) television ad user fee system.  Last week, FDA’s Division of Drug Marketing, Advertising, and Communications established a website dedicated to DTC user fee issues.  In addition, FDA issued its PDUFA IV Performance Goals.  A copy of the transmittal letter to Congress is available here, and the Performance Goals document is available here.  Information on medical device user fees is available here.  FDA’s drug and device user fee rates for Fiscal Year 2008 will be published in the Federal Register tomorrow.  Pre-publication versions of those notices are available here (drug) and here (devices).

    OIG Report Critical of FDA’s Clinical Trial Oversight

    The U.S. Department of Health and Human Services’ Office of Inspector General (“OIG”) recently issued a report critical of FDA’s clinical trial oversight along with recommendations to improve such oversight.  Congress requested the OIG report after a series of news articles published in 2005 highlighted various clinical trial vulnerabilities.  The objective of the report is two-fold: (1) to determine the extent to which FDA conducted inspections of clinical trials between Fiscal Years 2000 and 2005; and (2) to assess the Agency’s process for inspecting clinical trials.

    OIG found that FDA had no method in place to identify all clinical trials or Institutional Review Boards (“IRBs”), which are responsible for approving and monitoring research involving human subjects within their institution.  This lack of information reportedly impeded FDA’s ability to both inspect clinical trials and to ensure that IRBs are providing appropriate oversight.  The report also notes that FDA only inspected an estimated 1% of clinical trials, and that these inspections were spread across a number of different divisions within the Agency.  Further, nearly 75% of the inspections that did take place occurred only after the trial concluded, and were designed to assess the quality of the data rather than the safety of the human subjects involved.

    To remedy this problem OIG recommends that FDA take five steps to improve its clinical trial oversight:

    1. Develop a database that includes information on all clinical trials;
    2. Create an IRB registry;
    3. Create a database to allow inspection tracking between FDA components;
    4. Seek legal authority for clinical trial oversight; and
    5. Establish an institutional procedure to provide feedback to local FDA inspectors on their reports and findings.

    FDA concurred in all of the recommendations, except establishing a feedback mechanism (on which the Agency did not comment).

    The recently-enacted FDA Amendments Act includes new provisions intended to improve the availability of clinical trial information, including expanding the current clinical trial registry database and creating a new results database. The clinical trial database recommended in the OIG report would be a separate database for internal FDA use only. 

    Categories: Drug Development

    FDA Will Meet to Address Possible Behind-The-Counter Drug Availability

    On October 4, 2007, FDA issued a Federal Register notice announcing that the Agency will hold a public meeting to address the possible creation of a third category of drugs for the U.S. market – so-called Behind-the-Counter (“BTC”) drugs.  Such drugs would be available without a prescription, but only after intervention by a pharmacist.  Currently, the law only recognizes two categories of drugs – prescription and Over-the-Counter (“OTC”).  FDA states in the notice that the Agency would like to “explor[e] the public health benefit of certain drugs being available BTC that were previously prescription medications,” and that “BTC [drugs] could be comprised of certain medications available behind the counter at the pharmacy without a prescription and require the intervention of a pharmacist before dispensing.”  FDA seeks written comments on the BTC category by November 28, 2007.  The public meeting is scheduled for November 14, 2007.  Because seating is limited, people wishing to attend the meeting must register with FDA by November 5, 2007.

    Several other countries, including Australia, Canada, France, New Zealand, United Kingdom, Denmark, Germany, Italy, Netherlands, Sweden, and Switzerland, already recognize BTC drug status.  These countries generally use the following criteria to determine whether a drug’s switch from prescription to BTC class is warranted:  “(1) [i]ndications suitable for self-medication, including self-diagnosis, with the intervention of a pharmacist and (2) the medicine has a low potential for side effects or overdose, and intervention by a pharmacist could minimize these risks.” 

    FDA’s notice lists several issues that the Agency would like feedback on, including: (1) which drugs should be made available BTC and why; (2) whether BTC status should be used as a temporary or transitional status for drugs that move from prescription to OTC; (3) whether BTC availability will be cost-effective to patients; and (4) what impact BTC drugs will have on the practice of pharmacy.  Given the complex issues that a new BTC drug category raises, FDA will likely receive significant public input with widely varying points of view.  Indeed, there was considerable discussion and differing points of view expressed about BTC status in 2005 and 2006 when FDA considered various issues related to the prescription-to-OTC switch of the contraceptive drug PLAN B (levonorgestrel) Tablets.

    Moreover, FDA has previously considered and declined to create BTC drug status.  Specifically, in 2003, Pharmacists Planning Service, Inc., a non-profit organization that promotes consumer public health education and pharmaceutical information, submitted a citizen petition to FDA (that was later amended) requesting that the Agency “switch Nicotrol Inhaler (Nicotine Inhalation System) from prescription only to [OTC] status TO BE SOLD ONLY UNDER A PHARMACIST’S SUPERVISION as a third class of drugs.”  FDA denied the petition in April 2004 in a 3-page response without substantively discussing BTC status.

    By Cassandra A. Soltis

    Categories: Drug Development

    Congress Set to Consider Multiple Food-Related Bills

    In response to recent scares over tainted food imports and E.coli outbreaks in produce, several members of the U.S. House of Representatives and Senate have introduced (and plan to introduce) a variety of bills aimed at improving food safety and security.  In late September alone, three new bills were introduced.  In addition, two food safety-related amendments to the 2007 “Farm Bill” (H.R. 2419) are expected in the Senate.  Specifically, Representative John Dingell (D-MI) introduced a food safety import bill in the House, and in the Senate, Senators Sherrod Brown (D-OH) and Robert Casey (D-PA) introduced a food safety bill and Senator Tom Harkin (D-IA) introduced a produce safety bill.  Senator Richard Durbin (D-IL) announced plans for an amendment to the 2007 Farm Bill that would force Congress to reauthorize all food safety agencies in 2010, and Senator Harkin announced plans to propose an amendment to the Farm Bill to create a Food Safety Commission.  In addition, the recently-enacted FDA Amendments Act includes various food-related provisions (in Titles IX [Section 912] and X of the new law).

    As we previously reported, Rep. Dingell’s bill, the “Food and Drug Import Safety Act of 2007” (H.R. 3610), establishes user fees of up to $50 per line item of imported food and up to $1,000 per line item on imported drugs.  Not less than 90% of the fees would be used to fund inspections, and no more than 10% of the fees could be used for research.  The bill would also restrict food importation to specific points of entry, require food to be labeled with its country of origin, create a voluntary program for import companies to abide by specific food safety guidelines, enhance civil monetary penalties, prevent the U.S. Department of Health and Human Services (“DHHS”) from terminating or consolidating any FDA field laboratories or FDA district offices, increase food and drug inspections, and create labeling requirements for food containing carbon monoxide.  Rep. Dingell’s bill has already raised concerns over mounting user fees, and two House members, Rep. Gene Green (D-TX) and Rep. Janice Schakowsky (D-IL), question limiting imports to ports with an FDA lab, which could result in ports without an FDA lab losing a significant amount of business, including Houston and Chicago, and logjams at others. 

    Sen. Harkin’s bill, the “Fresh Produce Safety Act of 2007” (S. 2077), is much more narrow in scope and is specifically directed at improving the safety of fruits and vegetables.  The bill would require the inspection of facilities that process produce, and would require DHHS to establish standards for agricultural production, including standards for manure application management, exclusion of domestic animals during harvesting and growing season, water standards, and ground water monitoring.  The bill would also create a public education program related to food safety for fresh produce and require DHHS, in consultation with the U.S. Department of Agriculture (“USDA”), to promulgate regulations for equivalency with foreign nations that export produce to the U.S.

    Sens. Brown and Casey’s bill, the “Food and Product Responsibility Act of 2007” (S. 2081), is a lengthy bill that covers nearly all types of food and many consumer goods.  The bill would give greater authority to FDA and USDA to recall the products they regulate, and would require manufacturers to demonstrate the means to cover the cost of potential recalls before they can place their products into the stream of commerce.  Products covered in the bill include food, drugs, devices and cosmetics, biological products, consumer products, and meat, meat products, poultry, and poultry products, eggs and egg products.

    The 2007 Farm Bill, which the House passed earlier this year and the Senate Agriculture Committee is currently considering, has also become vehicle for food safety legislation.  Sen. Durbin, in an effort to force Congress to reform the current food safety system and place all food safety responsibilities in a single federal agency, announced on September 28th that he would propose an amendment to sunset all food safety agencies by 2010.  Sen. Harkin, who chairs the Senate Agriculture Committee, has voiced support for the proposed Durbin amendment, and has also announced plans for his own amendment to the Farm Bill.  The Harkin amendment would create a domestic food safety panel to work with President Bush’s import panel to recommend ways to improve food safety.  Sen. Harkin’s panel would be modeled after the 2002 Food Safety Commission, which never received the appropriations it needed to begin work. 

    At this point, with no fewer than 20 FDA-related bills circulating in Congress, the greatest barrier to passing meaningful legislation may be weeding through the sea of bills to decide which to pass and which to scrap. 

    By Susan J. Matthees

    Categories: Foods

    Bristol-Myers Squibb Achieves Global Resolution on Array of Historical Drug Pricing and Marketing Allegations

    On September 28, 2007, the U.S. Department of Justice announced that Bristol-Myers Squibb (“BMS”) agreed to pay more than $515 Million Dollars to settle off-label promotion, anti-kickback, Average Wholesale Price (“AWP”), and Best Price (“BP”) allegations, and related False Claims Act claims.  The enforcement action comes just three months after BMS earned praise from a federal monitor as a company “that today is governed by the highest standards of integrity, ethics and accountability, and one that reflects its commitment to those principles in both words and deeds,” and correspondingly, having a U.S. Attorney dismiss a two year old a criminal complaint and terminate a deferred prosecution agreement (“DPA”).  Despite the seeming inconsistency between glowing praise followed by new allegations and a large settlement, the settlement documents suggest that while this is not “old news,” the “covered conduct” stopped relatively shortly after the company entered into the DPA in June 2005.  Specifically, according to the government’s allegations, the covered conduct ceased in December 2001 (anti-kickback), December 2000 (AWP), December 2003 (anti-kickback again), December 2005 (off-label promotion), and 1997 (BP).

    The $515M includes a $328M federal share, $25M of which comes as disgorgement of profits under the FDC Act.  The states will share in $187M.  False Claims Act relators in seven actions will share $50M.

    As is usual in these types of resolutions, BMS also entered into a Corporate Integrity Agreement with the Office of the Inspector General for the U.S. Department of Health and Human Services.


    By James P. Ellison

    Categories: Enforcement

    FDA Announces New Generic Drug Initiative

    Earlier today, FDA announced a new initiative, called the Generic Initiative for Value and Efficiency (“GIVE”), which is intended to increase the number and variety of generic drug products.  According to Gary Buehler, R.Ph., Director of FDA’s Office of Generic Drugs (“OGD”):

    GIVE is an initiative aimed at optimizing OGD’s generic drug review process to increase efficiency. The goals of GIVE are to approve higher numbers of applications for generic products and expedite review of applications for which there are few generics available.

    Over the last three to four years, the number of [ANDAs] submitted to [OGD] has increased. This has led to a growing list of pending applications. We’ve made a number of successful process improvements during this time. In fact, the office approved a record number of applications during the past two years. We approved 510 products in 2006, and approved more than 650 in the fiscal year that just ended.

    But the advancement of medical science and the related increasing cost of health care and disease prevention have caused the role of OGD and its review staff to grow. The number of firms producing generic products and the number of products each firm proposes are growing at an unforeseen pace. The improvements we have made serve to unify and enhance the review process to address the growing workload, and to increase the efficiency of our office’s review efforts.

    As part of GIVE, FDA will revise the review order for certain ANDAs. “For example, first generic products, for which there are no blocking patents or exclusivity protections on the reference listed drug, are identified at the time of submission for expedited review. This will mean that these products, for which there are currently no generic products on the market, may reach the consumer much faster.”  Although there are about 215 full-time FDA staff working on ANDA reviews, under GIVE, FDA will also “hire and train new generic drug reviewers and focus on enhanced use of electronic programs for handling drug submissions and internal documents,” and, when possible, engage the efforts of other FDA components.  A diagram of how OGD will make more drugs available under GIVE is available here.

    OGD’s GIVE program is the latest of several initiatives intended to accelerate the generic drug development and approval processes.  Last year, OGD announced changes to its “First-In, First-Reviewed” policy to provide for exceptions under certain circumstances (see Orange Book Blog post).  In May 2007, FDA issued its “Critical Path Opportunities for Generic Drugs,” which identifies what FDA believes are challenges in the generic drug development process and outlines some actions intended to address those challenges (see FDA Law Blog post).  Also in May, FDA announced the availability of a draft guidance document and database providing recommendations on how to design product-specific bioequivalence studies to support ANDAs (see FDA Law Blog post).

    It is unclear the extent to which OGD’s GIVE initiative might or might not affect the Agency’s push for generic drug user fees.  Earlier this year, FDA proposed creating generic drug user fees as part of the Agency’s Fiscal Year 2008 budget.  The recently-enacted FDA Amendments Act does not include such a user fee program.

    House Committee Passes Dextromethorphan Distribution Act; DEA Reviewing for Possible Control

    On September 27, 2007, the U.S. House of Representatives Committee on Energy and Commerce passed H.R. 970, the Dextromethorphan Distribution Act of 2007, after a legislative “mark-up” session.  Similar legislation was introduced in the U.S. Senate in May 2007 (S. 1378) and was referred to the Health, Education, Labor, and Pensions Committee, where it has remained dormant.  Now that the House Energy and Commerce has passed the bill, it will be scheduled for a vote by the full House.

    H.R. 970, if enacted, would restrict the distribution and possession of raw dextromethorphan, an antitussive (i.e., cough-suppressant) drug found in many over-the-counter cold/cough drug products.  Specifically, the bill would restrict the distribution of unfinished dextromethorphan to anyone but FDA-registered drug manufacturers and the possession of unfinished dextromethorphan by anyone but registered drug manufacturers.  The bill defines the term “unfinished dextromethorphan” to mean “dextromethorphan that is not contained in a drug that is in finished dosage form.”

    Dextromethorphan is not a federally-controlled substance, but the Drug Enforcement Administration (“DEA”) recently noted that the Agency is reviewing the drug for possible control (that is, “scheduling”) under the Controlled Substances Act (“CSA”).  DEA observes that the 2006 “Monitoring the Future Study” showed that in 2005, 4% to 7% of 8th, 10th, and 12th graders reported using dextromethorphan for non-medical use.  DEA further reports that a California Poison Control System study showed a 10-fold increase of dextromethorphan abuse by all age groups from 1999 to 2004, and a 15-fold increase of abuse by adolescents during the period.

    Should DEA decide to schedule dextromethorphan as a controlled substance under the CSA, the Agency would most likely propose placement of the drug in Schedule IV or V (i.e., substances with a low potential for abuse and with a currently accepted medical use).

    By Larry K. Houck

    DOJ Settles with Five Hip and Knee Replacement Companies

    On September 27, 2007, the U.S. Attorney’s Office for the District of New Jersey announced settlements with five companies (Biomet, Inc., Depuy Orthopaedics, Smith & Nephew, Inc., Zimmer, Inc., and Stryker Orthopedics, Inc.) resolving anti-kickback allegations.

    The allegation common to all five cases is that each of the companies entered into consulting agreements with orthopedic surgeons under which the companies paid to induce the surgeons to use that company’s hip and knee replacement products.

    Resolution for the first four companies listed above was through a deferred prosecution agreement (“DPA”), civil settlement, and corporate integrity agreement (“CIA”).  Stryker Orthopedics, Inc., which according to the press release “cooperated with the U.S. Attorney’s Office before any other company,” entered into a non-prosecution agreement (“NPA”), but did not enter into any civil settlement agreement or CIA, and therefore, did not get a release from civil or administrative liability.

    All five companies have agreed to the appointment of federal monitors, who include former Attorney General John Ashcroft, and Debra Yang, the former U.S. Attorney for the Central District of California, whose investigation of Representative Jerry Lewis (R-CA), and somewhat abrupt departure from Gibson, Dunn & Crutcher LLP (the law firm representing Rep. Lewis), made headlines in connection with the U.S. Attorney firings earlier this spring.

    The criminal complaints, filed in connection with each of the four cases in which there is a DPA, allege conspiracy to violate the criminal anti-kickback statute, 42 U.S.C. § 1320a-7b(b)(2), in violation of the general criminal conspiracy statute, 18 U.S.C. § 371.  It appears that the alleged conspiracy was between each company and surgeons as co-conspirators.  There does not seem to be any allegation of inter-company conspiracy.

    The press release states that the civil releases resolve "claims under the anti-kickback statute and civil federal False Claims Act."  The settlement agreement summarily states that the "United States contends that certain of these financial arrangements were improper, that the remuneration paid thereunder was improper and/or unlawful, and that these arrangements caused hospitals and physicians to submit false and fraudulent claims. . . ."  Thus, it appears that the False Claims Act theory behind these settlements follows those cases in which the government has alleged that anti-kickback allegations necessarily give rise to false claims, a theory that is not tested in a settlement. 

    In a post-McNulty Memorandum footnote on the controversy over the U.S. department of Justice requesting waivers of the attorney-client privilege, each of the DPAs and the NPA is clear that the companies are not waiving attorney-client privilege or attorney work-product protection, which contrasts with a pre-McNulty Memorandum DPA from that Office.

    If last week’s activity from Senator Charles Grassley (R-IA), Ranking Member of the U.S. Senate Finance Committee, and False Claims Act champion, are any indication, resolution with the N.J. U.S. Attorney’s office may not put this matter behind these companies.  Senator Grassley sent a letter to Medtronic, which settled similar allegations in July of last year for $40M.  Senator Grassley nevertheless appears to want additional information from the company.


    By James P. Ellison

    Categories: Enforcement

    CDER Launches Drug Safety Newsletter

    On September 18, 2007, FDA’s Center for Drug Evaluation and Research (“CDER”) launched its latest publication, the “Drug Safety Newsletter”.  This quarterly electronic publication is intended as an additional source of drug safety information for healthcare professionals and complements existing communications targeted at healthcare professionals (i.e., prescription drug labeling, Healthcare Professional Sheets, FDA Alerts, and other information available on FDA’s website).

    With its new Drug Safety Newsletter, CDER hopes to “enhance communication of new drug safety information, raise awareness of reported adverse events, and stimulate additional adverse event reporting.”  Each newsletter will include postmarketing safety information obtained from the Agency’s review of adverse event reports, and from clinical trials and epidemiological studies, postmarketing safety information for “recently approved new molecular [entities]” and “recent advisories on drug safety that have been posted on FDA’s Web site.”  In addition to these recurring items, FDA plans to include “topics of special interest.”

    The first issue of the Drug Safety Newsletter includes postmarketing reviews of Rituximab, Modafinal, and Temozolamied, early safety findings of the new molecular entity Deferasirox, and FDA’s advisories on drug safety from January 1, 2007 through June 1, 2007.

    The electronic newsletter is free.  Anyone interested in receiving a copy can subscribe here.

    By Riëtte van Laack

    Categories: FDA News