By Kurt R. Karst –   

It was just yesterday that we commented on how folks in the Hatch-Waxman community have been patiently awaiting FDA’s decision on an October 2010 citizen petition (Docket No. FDA-2010-P-0545) requesting that the Agency not approve any ANDA for a generic version of XYZAL (levocetirizine dihydrochloride) that omits, via a “section viii” statement, information on seasonal and and perennial allergic rhinitis covered by U.S. Patent No. 5,698,558 (“the ‘558 patent”) – XYZAL’s so-called “primary indications.”  Earlier today, FDA responded.  FDA denied the petition and approved ANDAs with skinny labeling for chronic idiopathic urticaria – XYZAL’s so-called “secondary indication.”   The bottom line in FDA’s XYZAL petition decision is similar to many of the Agency’s previous labeling carve-out petitions:

permitting carve-outs for certain patent-protected indications for levocetirizine dihydrochloride would not require removal of safety information from the labeling or alteration of the labeling in such way that would render the drug products less safe or less effective than Xyzal for the remaining conditions of use.

The decision also gives us good reason to update our popular Generic Drug Labeling Carve-Out Citizen Petition Scorecard.  So here you go . . . .

Generic Drug Labeling Carve-Out Citizen Petition Scorecard

FDA Citizen Petition Responses Permitting a Labeling Carve-Out

• FDA Response, Docket Nos. 2001P-0495, 2002P-0191, 2002P-0252 (June 11, 2002) – ULTRAM (tramadol HCl)
• FDA Response, Docket No. 2001P-0495/PRC (Mar. 31, 2003) – ULTRAM (tramadol HCl)
• FDA Response, Docket No. FDA-2003-P-0074 (Apr. 6, 2004) – REBETOL (ribavirin)
• FDA Response, Docket No. FDA-2005-P-0368 (Dec. 1, 2006) – OXANDRIN (oxandrolone)
• FDA Response, Docket No. FDA-2006-P-0274 (Mar. 13, 2008) – ETHYOL (amifostine)
• FDA Response, Docket No. FDA-2007-P-0169 (Apr. 25, 2008) – MARINOL (dronabinol)
• FDA Response, Docket No. FDA-2008-P-0304 (June 18, 2008) – ALTACE (ramipril)
• FDA Response, Docket No. FDA-2008-P-0069 (July 28, 2008) – CAMPTOSAR (irinotecan HCl)
• FDA Response, Docket No. FDA-2006-P-0073 (Nov. 18, 2008) – PULMICORT Respules (budesonide inhalation suspension)
• FDA Response, Docket Nos. FDA-2008-P-0343 & FDA-2008-P-0411 (Dec. 4, 2008) – PRANDIN (repaglinide)
• FDA Response, Docket No. FDA-2008-P-0343/PRC and PSA & FDA-2008-P-0411 (June 16, 2009) – PRANDIN (repaglinide)
• FDA Response, Docket No. FDA-2009-P-0411 – ACTOS (pioglitazone HCl) & ACTOPLUS MET (March 15, 2010) (pioglitazone HCl; metformin HCl) 
•  FDA Response, Docket No. FDA-2009-P-0601 (June 17, 2010) – NAROPIN (ropivacaine HCl monohydrate)
• FDA Response, Docket No. FDA-2010-P-0087 (July 30, 2010) – LYRICA (pregabalin) 
• FDA Response, Docket No. FDA-2010-P-0545 (February 24, 2011) – XYZAL (levocetirizine dihydrochloride)

FDA Citizen Petition Responses Not Permitting a Labeling Carve-Out

• FDA Response, Docket No. FDA-2003-P-0002 (Sept. 20, 2004) – RAPAMUNE (sirolimus)

Pending Labeling Carve-Out Citizen Petitions

• Docket No. FDA-2007-P-0294 – ACTOS (pioglitazone)
• Docket No. FDA-2007-P-0113 – THALOMID (thalidomide)
• Docket No. FDA-2009-P-0597 – Fluticasone Propionate and/or Salmeterol Xinafoate Products
• Docket No. FDA-2010-P-0403 – VAGIFEM (estradiol)
• Docket No. FDA-2010-P-0614 – COLCRYS (colchicine)

BPCA Section 11 Pediatric Labeling Citizen Petitions

• FDA Response, Docket No. FDA-2001-P-0053 (January 24, 2002) – BPCA Implementation
• FDA Response, Docket No. FDA-2002-P-0289 (May 21, 2003) – ALPHAGAN (brimonidine)
• FDA Response, Docket No. FDA-2010-P-0545 (February 24, 2011) – XYZAL (levocetirizine dihydrochloride) 

Withdrawn or “Dead” Labeling Carve-Out Citizen Petitions

• Docket Nos. FDA-2004-P-0426 & FDA-2003-P-0081; FDA Letter – SKELAXIN (metaxalone) (see our previous post here)
• Docket No. FDA-2001-P-0445 – NEURONTIN (gabapentin) Capsules

By Ricardo Carvajal –

In a letter directed to Attorney General Eric Holder, Senator Patrick Leahy (D-VT) asked the U.S. Department of Justice (“DOJ”) for an update on its investigation of the Peanut Corporation of America (“PCA”) and its president, Stewart Parnell.  According to the letter, FDA determined that PCA knowingly distributed potentially contaminated food, and evidence suggests that PCA shopped for a testing laboratory that would provide favorable results.  Sen. Leahy contends that “it is critical [for DOJ] to determine whether these actions rise to the level of criminal conduct.”  The letter also cites the recent pistachio recall and egg-related salmonella outbreak as evidence that “wrongdoers are disregarding the health and safety of American consumers by choosing to sell contaminated products.”  The letter closes by noting that Sen. Leahy has introduced legislation to impose tougher penalties for certain food safety violations, and asks whether DOJ “needs any additional tools to protect the American people.”

By Kurt R. Karst –      

As folks in the Hatch-Waxman community patiently await FDA’s decision on an October 2010 citizen petition (Docket No. FDA-2010-P-0545) requesting that the Agency not approve any ANDA for a generic version of XYZAL (levocetirizine dihydrochloride) with skinny labeling that omits, via a “section viii” statement, information on allergic rhinitis covered by U.S. Patent No. 5,698,558 (“the ‘558 patent”), we read with interest a decision from the U.S. District Court for the Eastern District of North Carolina (Western Division) on a related issue.

The North Carolina case stems from a May 2008 Paragraph IV patent certification Sandoz, Inc. made with respect to the ‘558 patent, and a timely filed patent infringement lawsuit triggering a 30-month stay of ANDA approval.  The ‘558 patent, which expires on September 24, 2012 and is subject to a period of pediatric exclusivity that expires on March 24, 2013, is listed in the Orange Book as a method-of-use patent with a U-812 patent use code defined as “RELIEF OF SYMPTOMS ASSOCIATED WITH SEASONAL AND PERENNIAL ALLERGIC RHINITIS.”  In February 2010, Sandoz allegedly revised its Paragraph IV certification to the ‘558 patent to a section viii statement, requesting approval for its proposed generic version of XYZAL for what the NDA holder has characterized in the above-referenced citizen petition as the “secondary indication,” chronic idiopathic urticaria, and that carves out the “primary indications,” namely seasonal and perennial allergic rhinitis.

Given the change from a Paragraph IV certification to a section viii statement, Sandoz filed a Motion to Dismiss arguing that the District Court no longer had subject matter jurisdiction over the litigation.  The plaintiffs in the case filed their own motion – a Motion to Extend Sandoz’s Thirty-Month Stay – arguing that Sandoz “has not reasonably cooperated in expediting this litigation.”  Naturally, Sandoz opposed the motion, and argued that it should be denied for at least three reasons: “(1) the Court lacks subject matter jurisdiction over Sandoz’s section viii ANDA filing, (2) the 30-month stay is inapplicable to ANDA applicants proceeding under section viii, and (3) Sandoz has not unreasonably delayed this action.”

Under the FDC Act, a timely filed patent infringement lawsuit in response to a Paragraph IV certification means that “the [ANDA] approval shall be made effective upon the expiration of the [30-month stay] . . . or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action . . . .”  FDC Act § 505(j)(5)(B)(iii) (emphasis added).  Since the enactment of the Hatch-Waxman Amendments in 1984, it has been quite uncommon for a court to extend the statutory 30-month stay on ANDA approval.  In 2009, for example, the U.S. Court of Appeals for the Federal Circuit in Eli Lilly & Co. v. Teva Pharms. USA, Inc., 557 F.3d 1346 (Fed. Cir. 2009) affirmed a district court decision extending a 30-month stay with respect to an ANDA for a generic version of EVISTA (raloxifene HCL) Tablets.

Relying, in part, on a 2009 decision out of the U.S. District Court for the Eastern District of Wisconsin concerning an animal drug and the animal drug Hatch-Waxman counterpart, the Generic Animal Drug and Patent Term Restoration Act (Bayer Healthcare, LLC v. Norbrook Labs. Ltd., No. 08 C 0953, 2009 U.S. Dist. LEXIS 126929 (E.D. Wis. Sept. 24, 2009)), the North Carolina District Court denied Sandoz’s Motion to Dismiss.  The Court concluded that that was no evidence “to demonstrate that the FDA must or in fact has accepted the withdrawal of the Paragraph IV certification, or that the FDA will allow Sandoz to amend its application to include a section viii statement and ‘carve out’ information related to allergic rhinitis,” and that “Sandoz’s failure to cite any authority for the proposition that jurisdiction under section 271(e)(2) requires that an ANDA filer maintain a ‘Paragraph IV’ certification dooms its position” (internal quotation omitted; emphasis added).  As such the Court concluded that subject matter jurisdiction over the litigation is maintained. 

Given this conclusion, the Court rejected Sandoz’s arguments that an extension of the 30-month stay is inapplicable and proceeded to identify examples that the Court deemed sufficient to demonstrate that Sandoz failed to “reasonably cooperate in expediting the action” and that warranted an extension of the 30-month stay under FDC Act § 505(j)(5)(B)(iii) – namely failure to timely produce a privilege log and to comply with the Court’s discovery orders.  Accordingly, the Court extended the 30-month stay by 60 days, until January 27, 2011.

Now that the extended 30-month stay has ended, it would seem that the only block to an approval decision on any pending ANDAs containing a section viii statement to the ‘558 patent is FDA’s decision on the October 2010 citizen petition.  Although FDA has already approved one ANDA for generic XYZAL Tablets – ANDA No. 90-229 – that application contains a Paragraph IV certification to the ‘558 patent.  The sponsor qualified for 180-day exclusivity, which according to the most recent Orange Book Cumulative Supplement has not yet been triggered by commercial marketing, but that exclusivity would not prevent FDA from taking action on ANDAs containing a section viii statement to the ‘558 patent, just subsequent ANDAs containing a Paragraph IV certification to the patent.  Depending on (or perhaps regardless of) how FDA rules on the pending citizen petition, it is possible that the battle over generic XYZAL is far from over.

By Peter M. Jaensch –

United States Senator Charles Schumer (D-NY) recently introduced legislation that is intended to prevent sales of recalled biologics, drugs, medical devices, infant formula, and foods.  However, if that legislation is enacted it  may actually dissuade companies from undertaking voluntary recalls.

On February 14, 2011, Sen. Schumer introduced S. 330, the “Consumer Recall Protection Act of 2011,” which, if enacted, would prohibit sales “to a consumer of a covered product that is subject to a recall,” except  where the “defect was remedied” and the seller notifies the consumer of the “recall, defect, and remedy” prior to sale.  Among other products, the bill covers “[f]ood, drugs, devices, and cosmetics” as defined in the FDC Act.  The bill defines various triggers for when a product is considered to be subject to a recall.  Although specific triggers are provided for medical devices and infant formula, other products are considered subject to a recall whenever there is a “recall of the . . . product by the manufacturer or distributor in response to an advisory or other alert issued by the Commissioner of Food and Drugs that advises consumers to avoid the . . . product.”

The bill is at best ambiguous.  For example, what constitutes an “alert” or an “advisory,” and when is a recall considered to have begun “in response” to such notifications? Moreover, if enacted, S. 330 may actually reduce self-enforcement by companies.  As currently written, S.330 would appear to apply even when there is not a safety issue associated with the “recall.”  Under these and other circumstances, a manufacturer might well think twice about commencing a recall at all if the manufacturer will be prohibited from selling “recalled” products.

There is one particularly interesting bureaucratic feature in the legislation.  Even though the trigger for the prohibition of sales is largely tied to actions of the FDA, that agency would not enforce the legislation.  Instead, Sen. Schumer proposes that the Federal Trade Commission would enforce the legislation if it is enacted.

By Kurt R. Karst –      

Last week, substantively identical legislation was introduced in both the U.S. House of Representatives and in the U.S. Senate to amend the FDC Act to prohibit the manufacture, marketing, sale, or distribution of an authorized generic version of an NDA-approved drug until any period of 180-day exclusivity associated with an ANDA for a generic version of that NDA-approved drug has expired or has been forfeited.  The Senate version of the bill, S. 373, is titled the “Fair Prescription Drug Competition Act.”  The bill was introduced by Sen. John Rockefeller (D-WV), and is co-sponsored by Sens. Daniel Inouye (D-HI), Patrick Leahy (D-VT), Charles Schumer (D-NY), Jeanne Shaheen (D-NH), and Debbie Stabenow (D-MI).  The House version of the bill, H.R. 741, was introduced by Rep. Jo Ann Emerson (R-MO).  The bills introduced in the 112th Congress to ban authorized generics during the pendency of 180-day exclusivity are the latest iterations of legislation that dates back to at least the 110th Congress, when Rep. Emerson and Sen. Rockefeller introduced H.R. 806 and S. 438, respectively – see our previous post here.

Both S. 373 and H.R. 741 would amend FDC Act § 505 to add new subsection (w) – “Prohibition of Authorized Generic Drugs” – to state:

(1) IN GENERAL- Notwithstanding any other provision of this Act, no holder of a new drug application approved under [FDC Act § 505(c)] shall manufacture, market, sell, or distribute an authorized generic drug, directly or indirectly, or authorize any other person to manufacture, market, sell, or distribute an authorized generic drug.

(2) AUTHORIZED GENERIC DRUG- For purposes of this subsection, the term ‘authorized generic drug’ –

(A) means any version of a listed drug (as such term is used in [FDC Act § 505(j)]) that the holder of the new drug application approved under FDC Act § 505(c)] for that listed drug seeks to commence marketing, selling, or distributing, directly or indirectly, after receipt of a notice sent pursuant to [FDC Act § 505(j)(2)(B)] with respect to that listed drug; and

(B) does not include any drug to be marketed, sold, or distributed –

(i) by an entity eligible for 180-day exclusivity with respect to such drug under [FDC Act § 505(j)(2)(B)(iv)]; or

(ii) after expiration or forfeiture of any 180-day exclusivity with respect to such drug under [FDC Act § 505(j)(5)(B)(iv)].

S. 373 would also make a technical, conforming change with respect to the applicability of the definition of “authorized generic drug” at FDC Act § 505(t)(3).  FDC Act § 505(t) – “Database for Authorized Generic Drugs” – was added to the law by Section 920 of the 2007 FDA Amendments Act and requires FDA to compile and publish a complete list of all authorized generic drugs identified in annual reports submitted to the Agency since January 1, 1999.  On July 28, 2009, FDA issued final regulations implementing FDC Act § 505(t) – see our previous post here.  FDA also maintains an online database of authorized generic drugs. 

According to Sen. Rockefeller, “the 180-day exclusivity incentive to launch a patent challenge [created by the Hatch-Waxman Act] is being widely undermined by authorized generics,” which are “becoming even more prevalent as patents on some of the best-selling brand name pharmaceuticals expire.”  Passage of the Fair Prescription Drug Competition Act would, according to Sen. Rockefeller, “revitalize and protect the true intent of the 180-day marketing exclusivity period created in the Hatch-Waxman Act.”

The issue of marketing an authorized generic during the pendency of an ANDA sponsor’s 180-day exclusivity has touched each branch of the federal government.  (See an article we published on the topic a few years ago in RAPS Focus.)  In July 2004, FDA denied two citizen petitions (Docket Nos. FDA-2004-P-0400 and FDA-2004-P-0146) challenging the marketing of authorized generics.  FDA concluded, in part, that “[t]he marketing of authorized generics during the 180-day exclusivity period is a long-standing, pro-competitive practice, permissible under the [FDC Act].”  FDA’s petition decisions were challenged in court, but the Agency ultimately prevailed.  (FDA has not yet substantively responded to a third petition – Docket No. FDA-2004-P-0401.)

In June 2009, the Federal Trade Commission (“FTC”) announced the publication of an interim report, titled “Authorized Generics: An Interim Report,” presenting the first set of results from an FTC study conducted at the request of several members of Congress to examine the short-term and long-term effects of authorized generics on competition in the prescription drug marketplace – see our previous post here.  According to the report, “drug prices are lower when authorized generics are marketed against a single generic drug than when they are not.”  The FTC has not yet issued a more comprehensive report on the topic. 

By Riëtte van Laack –

As previously reported, on Dec. 8, 2010, FDA published a proposal to amend the interim final rule ("IFR") governing health claims concerning the risk of cardiovascular heart disease and consumption of phytosterols (see 21 C.F.R. § 101.83).  FDA stated that, as of February 22, 2011, it intended to discontinue its policy of enforcement discretion that had been in effect since 2003 concerning certain health claims that go beyond the IFR.  Based on comments and petitions by industry contending that more than 75 days were needed to relabel and reformulate products (see our prior post here), FDA decided to extend the 2003 enforcement discretion policy until February 21, 2012.  FDA’s decision does not constitute a response to the petitions it received in response to the proposed rule. 

By Ricardo Carvajal –

Totally Wicked-E.Liquid (“TWI”), an importer and distributor of electronic cigarettes, filed suit to prevent FDA from regulating TWI’s electronic cigarettes as drugs, devices, or combination products, and from barring their importation into the U.S.  TWI claims that the nicotine in its product is derived from tobacco, and that the product is therefore subject to regulation as a tobacco product and not as a drug, device, or combination thereof – an issue that the D.C. Circuit Court of Appeals recently decided in industry’s favor.  TWI contends that “FDA’s actions in barring TWI’s imports, in addition to being ultra vires, are thus the very definition of ‘arbitrary and capricious.’”

By Peter M. Jaensch & John A. Gilbert –

Since the passage of the federal Combat Methamphetamine Epidemic Act in 2005 and state legislation adopted in most states around the same time, retail sales of over-the-counter (“OTC”) cold and allergy products containing pseudoephedrine (“PSE”) have been subject to strict controls.    These restrictions include daily and monthly purchase and sale gram limits, logbook requirements and other security measures such as requiring that the products be sold from “behind the counter.”   Two states, however – Oregon and Mississippi – have further restricted sales of these products by requiring they be dispensed only pursuant to a prescription and scheduling them as controlled substances under the states’ controlled substance laws.  Because of the continued concern about diversion of OTC PSE products, a number of states in this legislative season are contemplating taking similar action. 

Last year, Georgia, Illinois, Missouri, and Washington introduced similar bills requiring prescription-only purchases and scheduling the products as controlled substances – most did not emerge from committee review.  This year, in what seems to be a trend towards increased state regulation, the legislatures in Hawaii, Indiana, Kentucky, Tennessee and Virginia also recently introduced bills to schedule these substances and to require prescriptions in order to purchase products containing pseudoephedrine or other methamphetamine precursors.

These bills are similar in that they generally propose to schedule or reschedule all PSE products as controlled substances (e.g., Schedule III), thus requiring that the products only be dispensed pursuant to a prescription.  For example, in Hawaii, a senate bill introduced on January 20, 2011, adds “any material, compound, mixture, or preparation which contains any quantity of [pseudoephedrine]” to the list of substances classified as Schedule III controlled substances, and amends existing laws to eliminate provisions relating to the procedures for OTC sales of pseudoephedrine products.  In Indiana, Senate Bill 474 similarly classifies any “material, compound, mixture, or preparation that contains a quantity of  [ephedrine or pseudoephedrine]” as a Schedule III controlled substance, thus available only by prescription.  The bill was introduced on January 13, 2011, and to date has not been subject to a vote.

Of the new legislation we have reviewed to date, proposed legislation in Kentucky appears to be the most aggressive.  One bill would require that methamphetamine precursors such as ephedrine, pseudoephedrine, or phenylpropanolamine be classified as Schedule IV controlled substances, available only by prescription.  The proposed law would also prohibit any practitioner from dispensing more than 9 grams of such products to any one patient over a 30-day period and limits refills over a 30-day period.  In a competing bill, another Kentucky senator has introduced legislation that would create a registry of individuals convicted of felonies related to illicit use of precursor chemicals or methamphetamine.  Such individuals would be prohibited from purchasing PSE OTC products; however, the current draft of the legislation would exempt individuals who received the product by prescription.  This is similar to the current law in Oklahoma, which also has established a registry to block certain individuals from purchasing PSE.    

In Nevada, a state senator submitted a “Bill Draft Request” calling for a bill that would, “Require[]… products containing ephedrine, pseudoephedrine and phenylpropanolamine to be dispensed by prescription only unless the product is formulated to prevent conversion to methamphetamine.”  The Nevada legislature convened on February 7, 2011, and we are advised that a bill will be forthcoming.

The introduction of these state bills reflects a perception among the states that the current federal and state restrictions are not sufficient to prevent the diversion of PSE cold and allergy products.  It is unclear, however, whether requiring a prescription or scheduling the drug will make a difference in preventing diversion of PSE.  Such action will make it more difficult and costly for individuals to obtain these medicines for legitimate use.  We will continue to follow these and other similar state bills, and report on significant developments including whether there is any federal legislation introduced along these same lines.

By Kurt R. Karst –      

The tome that is the President’s Budget for Fiscal Year 2012 is chock-full of new proposals that, if implemented, would significantly affect both brand-name and generic drug manufacturers. 

What first caught our attention were some statements in an overview of the proposed FY 2012 budget for the Department of Health and Human Services that:

The Administration will accelerate access to more affordable pharmaceuticals that will lead to cost savings for consumers and health programs across the Federal Government.  The President’s Budget includes two proposals to increase availability of generic drugs by providing the Federal Trade Commission [(“FTC”)] authority to stop drug companies from entering into anticompetitive agreements intended to block consumer access to safe and effective generics, and hastening availability of generic biologics while retaining the appropriate incentives for research and development for the innovation of breakthrough products.

Another budget document, titled “Terminations, Reductions, and Savings” provides a little more detail on these proposals.  Both of these issues were topics discussed in President Obama’s 2009 10-year budget proposal.

With respect to patent settlement agreements, which opponents refer to as pay-for-delay agreements, the President’s Budget says that “[t]he Administration proposal would give the [FTC] the authority to prohibit pay-for-delay agreements in order to facilitate access to lower-cost generics.”  This is authority the FTC has craved for years now, and that according to President Obama’s budget proposal would yield savings of $8,790,000,000 between 2012 and 2021.  As we recently reported, in January, Senator Herb Kohl (D-WI), along with several other Senators, introduced S. 27, the Preserve Access to Affordable Generics Act.  The bill, like its predecessor versions introduced, amended, and debated in the 111th Congress, would amend the Federal Trade Commission Act to permit the FTC to “initiate a proceeding to enforce the provisions of [new Sec. 28] against the parties to any agreement resolving or settling, on a final or interim basis, a patent infringement claim, in connection with the sale of a drug product.”  Such agreements, if challenged, would be presumptively anticompetitive and unlawful unless it can be demonstrated “by clear and convincing evidence that the procompetitive benefits of the agreement outweigh the anticompetitive effects of the agreement.” 

With respect to the 12-year period of reference product exclusivity created by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), President Obama’s FY 2012 budget says that:

Under current law, innovator brand biologics have 12 years of exclusivity and broad “evergreening” authority, whereby innovator manufacturers are able to make relatively minor changes to the “potency, purity, and safety” of their products to receive an additional 12 years of exclusivity. 

Under the Administration proposal, beginning in 2012, innovator brand biologic manufacturers would have 7 years of exclusivity and would be prohibited from receiving additional exclusivity by “evergreening” their products. 

The Obama Administration estimates that the change in reference product exclusivity  would yield savings of $2,340,000,000 between 2012 and 2021.

The issue of so-called “evergreening,” which is the practice of obtaining additional periods of exclusivity for product modifications, along with the period of reference product exclusivity were hotly debated during consideration of what ultimately became the BPCIA.  According to a December 21, 2010 letter signed by the three principal authors of the BPCIA, evergreening is not a concern because the BPCIA “is clear that no product, under any circumstances, can be granted ‘bonus’ years of data exclusivity for mere improvements on a product.”  The letter goes on to note, however, that “if a ‘next generation’ product is approved by the FDA as a new product (significant changes in safety, purity, or potency) then that new biologic will receive its own 12-year period of data exclusivity.”

The President’s FY 2012 Budget (here beginning on page 227, and here beginning on page 437) also proposes the creation of new user fees. 

The first new fee is the much-ballyhooed generic drug user fee.  Under the President’s proposal, the generic drug user fee charge would be an amount not to exceed $40,122,000 and “would be used to improve review times and reduce the current backlog of applications.”  As we recently reported, the ANDA backlog in FDA’s Office of Generic Drugs (“OGD”) continued to grow unabated in 2010, for a grand total of 2,361 original ANDAs pending at the close of 2010, and with an estimated median approval time of 31 months.  (According to the latest OGD statistics, the ANDA review backlog dipped slightly in January 2011 to 2,356 original ANDAs; however, the number of ANDAs pending more than 180 days continued to grow, from 1,816 ANDAs to 1,836 ANDAs.)

The President’s FY 2012 Budget would also create a new “reinspection fee for medical products” in an amount not to exceed $14,108,000.  According to the proposal, “FDA conducts post-market inspections of manufacturers of human drugs, biologics, animal drugs, and medical devices to assess their compliance with Good Manufacturing Practice and other regulatory requirements. The Budget includes a proposal to enable FDA to assess fees for follow-up reinspections that are required when violations are found during initial inspections.”  President Bush made a similar proposal in his FY 2009 budget request. 

Finally, the Obama Administration’s budget proposal includes a new “international courier user fee” in an amount not to exceed $5,338,000.  According to the budget proposal, “[t]he volume of imports, predominantly medical products, being brought into the United States by international couriers is growing substantially. To ensure the safety of these FDA regulated products through increased surveillance efforts, the Budget includes a new user charge to international couriers.”

Each of the user fee proposals is contingent upon the enactment of authorizing legislation.  Generic drug user fees, along with generic drug labeling preemption, may be among the most talked about topics at the GPhA Annual Conference taking place in Orlando later this week.

By Jeffrey K. Shapiro –

FDA’s Center for Devices and Radiological Health (“CDRH”) has proposed the “Innovation Pathway Program” for breakthrough medical devices.  CDRH says it will review these products in 150 days or less, which the agency claims is nearly half the review time of most premarket approval (“PMA”) applications.  The first product in the program is from the Defense Advanced Research Projects Agency (“DARPA”).  It is a brain-controlled, upper-extremity prosthetic device, which uses a microchip implanted on the surface of the brain to restore near-natural arm, hand, and finger function to patients suffering from spinal cord injury, stroke, or amputation.

Color us skeptical.  Not about the DARPA product.  We’re talking about the Innovation Pathway Program.

First of all, this program even at its best will affect probably just one or two products each year.  In other words, it is a very narrowly focused program.

Second, for many years, CDRH has had an Expedited Review procedure in place to speed approval of “breakthrough technology.”  Even CDRH has admitted it has not very worked well. 

The Innovation Pathway apparently is intended to improve CDRH’s track record with innovative products.  It would work like this:  CDRH will issue an Innovation Pathway Memorandum with a proposed roadmap and timeline for the development, clinical assessment, and regulatory review of the device.  The product would be assigned a case manager and reviewed by the Center Science Council, which is a new oversight body being developed within CDRH.  The Council will consist of senior managers and experienced scientists. 

As with the Expedited Review program, enrollment in the Innovation Pathway Program would not change the scientific or regulatory standards that CDRH uses to review submissions and authorize products for marketing.

As we said, color us skeptical.  The DARPA brain controlled prosthetic obviously has amazing potential, and FDA likely would have rushed it through in any event.  We’ll know if this new program has any value if additional products actually start speeding down the Innovation Pathway.

It already looks like that won’t happen any time soon.  CDRH said it will now seek comments from the public on this pathway before it is used again.  CDRH will host a public meeting on the Innovation Pathway program on March 15, 2011 at FDA’s White Oak campus.

This public outreach suggests the program announcement has been designed around the single DARPA product, and is not ready for prime time.  There will be a delay just to hold a public meeting and then digest the comments and further revise the program.

All of which suggests that it will be quite some time before another product is so lucky as to be allowed to speed down the Innovation Pathway.

We would prefer that CDRH work on significantly reducing the review times for all products, for both innovative and same-old, same-old technology.  That would be an innovation CDRH could be proud of.

By Riëtte van Laack –

Over the past two years, we have noted several joint or coordinated actions by FDA and FTC.  The agencies issued their own warning letters to the same manufacturers at the same time (here and here), and, on several occasions, FDA and FTC issued joint warning letters (here and here).  A recent warning letter by FDA to a dietary supplement company suggests a surprising new joint approach by FDA and FTC.

The February 1, 2011 warning letter to Tennessee Scientific, Inc/Scientific Formulations LLC bears only the signature of the FDA District Director.  However, the letter cites not only violations of FDC Act, but also potential violations of the FTC Act, and cites FTC’s substantiation requirement for advertising claims that a product can prevent, treat, or cure human disease.  Moreover, the letter includes a threat of potential action by FTC.  The letter directs the recipient to respond to these concerns directly to the FTC.  The letter is further evidence (as if any were needed) of the close working relationship that has evolved between the two agencies. 

By Kurt R. Karst –      

Late last year, Impax Laboratories, Inc. (“Impax”) filed a Complaint in the U.S. District Court for the District of New Jersey seeking a judgment with respect to U.S. Patent No. 6,911,217 (“the ‘217 patent”).  The ‘217 patent is one of four patents listed in the Orange Book for Pfizer, Inc.’s (“Pfizer’s”) DETROL LA (tolterodine tartrate) Extended Release Tablets, 4mg and 2mg.  (The other patents are U.S. Patent Nos. 5,382,600 (“the ’600 patent”), 6,630,162 (“the ‘162 patent”), and  6,770,295 (“the ‘295 patent”), which expire on March 25, 2012, November 11, 2019, and August 26, 2019, respectively, but are each subject to a 6-month period of pediatric exclusivity.)  Impax’s Complaint requests that the court rule that the company’s proposed generic version of DETROL LA, which is the subject of ANDA No. 90-235 containing a Paragraph IV certification to each of the four Orange Book-listed patents, does not infringe any claim of the ‘217 patent. 

Impax, which is apparently not a first applicant eligible for 180-day exclusivity – FDA’s Paragraph IV Certification List says that the first ANDA containing a Paragraph IV certification for an Orange Book-listed patent covering DETROL LA was received as of July 30, 2007 – was sued a few years back based on the company’s Paragraph IV certifications to the ‘600, ‘162, and ‘295 patents, but was not sued on the ‘217 patent.  Pfizer subsequently granted Impax a covenant not to sue with respect to the ‘217 patent.  According to Pfizer’s recent Motion to Dismiss the Impax Complaint, which argues for dismissal based on, among other things, a lack of subject matter jurisdiction, another company is the only first applicant eligible for 180-day exclusivity. 

There has been quite a bit of patent infringement litigation over the DETROL LA Orange Book patents involving various ANDA sponsors.  We will not get into that here.  The bottom line is that with its declaratory judgment action, Impax is attempting to create a court decision to trigger 180-day exclusivity under the failure-to-market forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I).  Notably, however, FDA has not tentatively approved any ANDA for a generic version of DETROL LA.  While that does open the door to a possible forfeiture of 180-day exclusivity under FDC Act § 505(j)(5)(D)(i)(IV) for failure to obtain tentative approval within 30 months of ANDA submission, it also raises questions about the circumstances under which a subsequent ANDA sponsor can trigger a first applicant’s 180-day exclusivity.

Under the 180-day exclusivity failure-to-market forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I), there must be two events, or “bookends,” to calculate a “later of” event between items (aa) and (bb).  The first bookend date under item (aa) is 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

The other bookend – the (bb) part of the equation – provides that the (bb) date is “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 [Paragraph IV] certification qualifying the first applicant for the 180-day exclusivity period,” one of three events occurs:

(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 [FDC Act § 505(j)(5)(D)(i)(I)(bb)(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 subsection (b).

The (AA) and (BB) court decision events under item (bb) can be triggered in patent infringement litigation by “the first applicant or any other applicant (which other applicant has received tentative approval)” (emphasis added).  

FDA has not yet, to our knowledge, addressed the “which other applicant has received tentative approval” parenthetical at FDC Act § 505(j)(5)(D)(i)(I)(bb).  What is not clear from the statute is whether the order of events counts.  It seems there are three possibilities with respect to a subsequent applicant who obtains tentative approval:

The first possibility is if a subsequent applicant first obtains tentative approval and then a final court decision in its favor.  Under this scenario, the statute seems clear that the 75-day period under (bb) begins on the date of that final court decision.  The first applicant’s 180-day exclusivity would be forfeited 75 days later (provided there is an (aa) event), unless a first applicant commercially markets before the 75-day date. 

Indeed, this was the case with FDA’s recent approval of Teva’s ANDA No. 77-983 for a generic version of Lilly’s GEMZAR (gemcitabine for injection), 1 gram/Single-use Vial & 200 mg/Single-use Vial.  As a first applicant, Teva qualified for 180-day exclusivity.  Another, subsequent ANDA sponsor, Sun Pharmaceuticals, obtained tentative approval for its ANDA No. 78-433 on March 4, 2008.  Sun was involved in patent infringement litigation with Lilly with respect to a patent on which Teva qualified for 180-day exclusivity.  The district court ruled in Sun’s favor, and Lilly appealed to the U.S. Court of Appeals for the Federal Circuit.  In July 2010, a panel of Federal Circuit judges affirmed the district court decision.  Lilly petitioned the Court for a panel rehearing/rehearing en banc, which the Court denied on November 1, 2010.  On November 12, 2010, the Federal Circuit issued its mandate, and Lilly has reportedly now petitioned the U.S. Supreme Court to review the decision.  FDA considered the date of issuance of the mandate to be a final court decision for purposes of triggering the 75-day clock under FDC Act § 505(j)(5)(D)(i)(I)(bb).  The date that was 75 days after November 12, 2010, and the date a forfeiture of 180-day exclusivity would have occurred was January 26, 2011.  However, FDA approved ANDA No. 77-983 on January 25, 2011 – one day short of the 180-day exclusivity forfeiture date.

A second possibility is if the subsequent applicant first obtains a final court decision in its favor and then tentative approval.  Under this scenario, it is unclear when the 75-day period begins.  FDA could interpret the statute such that the 75-day period is retroactive to the date of the final court decision.  Alternatively, FDA could interpret the statute such that the 75-day period begins on the date on which the subsequent applicant completed the statutory criteria.  That is, the 75-day period would begin on the date the subsequent applicant obtains tentative approval. 

Finally, under a third scenario, a subsequent applicant could, as under the second scenario, first obtain a final court decision in its favor and then tentative approval.  But instead of triggering the 75-day date, FDA could interpret the statute such that the final court decision does not trigger the 75-day period.  Under this interpretation, the order of events is critical.  That is, for the 75-day period to be triggered, a subsequent applicant must have tentative approval at the time there is a final court decision.  If not, then under this interpretation, the a final court decision has no effect and there is not a (bb) bookend event to cause a forfeiture of 180-day exclusivity.    

So how does all of this tie into Impax’s declaratory judgment action concerning DETROL LA?  At this time, FDA has not tentatively approved Impax’s ANDA (or any other ANDA).  Admittedly, a final court decision may be far off, during which time FDA could very well grant tentative approval.  However, with what appears to be a growing  number of declaratory judgment actions to trigger 180-day exclusivity (see, e.g., here and here), the chances also grow that a final court decision could come at a time before FDA has granted tentative ANDA approval.  

By Susan J. Matthees –

Six inmates on death row in three different states sued FDA in the U.S. District Court for the District of Columbia over the importation of thiopental sodium, one of the drugs used by some states to administer a lethal injection.  The plaintiffs are asking for a declaratory judgment that imported thiopental is a misbranded, adulterated, and unapproved new drug and cannot be lawfully imported into the country, and that FDA’s recent actions allowing importation of foreign thiopental are contrary to law, arbitrary, capricious, and/or an abuse of discretion under the Administrative Procedure Act (“APA”).  The plaintiffs also seek a permanent injunction prohibiting FDA from releasing any future shipments of imported thiopental and an order compelling FDA to recover and remove from interstate commerce all shipments of foreign thiopental that have been released into interstate commerce in the last 12 months.

Thiopental, which was developed in the 1930s to induce general anesthesia, was manufactured in the U.S. until 2009.  Because thiopental is not available in the U.S., states using it for administration of the death penalty have been importing the drug from Europe and FDA has allowed that importation.  The complaint states that FDA must deny admission to imported thiopental because it is a misbranded, adulterated, and unapproved new drug.  The plaintiffs allege that imported thiopental is misbranded because it fails to include adequate warnings and other required information on the label, and because it was manufactured in a facility that has not registered with the FDA. The plaintiffs allege that imported thiopental is adulterated because it is not manufactured in accordance with FDA’s GMP regulations and it does not conform to the standard formulation established by the official United States Pharmacopeia. 

The complaint also alleges that FDA’s actions with regard to permitting the importation of thiopental are inconsistent with FDA’s regulations, procedures, and established practice.  As an example, the plaintiffs point to recent cases where states attempted to import foreign drugs from Canada and FDA intervened to prevent such importation.  The plaintiffs also cite several cases that upheld FDA’s decisions not to allow drugs to be imported by states. 

However, FDA has long taken the position that it will exercise enforcement discretion and defer to law enforcement on matters involving pharmaceuticals for lethal injection.  In 1985, the U.S. Supreme Court held in Heckler v. Chaney, 470 U.S. 821 (1985), that FDA does have discretion not to investigate or commence proceedings for violation of FDC Act § 331 (which prohibits introduction into commerce an adulterated or misbranded drug).  Plaintiffs distinguish Heckler from their case on the basis that Heckler does not address FDA’s obligations under FDA Act § 801, which directs FDA to refuse admission of a drug into the U.S. that appears to be adulterated or misbranded.  The plaintiffs also state that Heckler addressed the unapproved use of approved drugs, whereas their case is about the importation of an unapproved, adulterated, and misbranded drug.  Further, the complaint argues that FDA does not have discretion to allow unapproved new drugs to be shipped or sold in the U.S. and that FDA cannot permit the marketing of an unapproved new drug.

By Cassandra A. Soltis –

The Dietary Guidelines for Americans, 2010 (the 2010 Dietary Guidelines), released by the federal government last week, were clearly drafted with the U.S. obesity epidemic in mind.  In addition to encouraging consumers to exercise more and reduce calorie consumption, the guidelines call on consumers to eat more nutrient-dense foods and beverages, reduce sodium intake to less than 2,300 mg (and to 1,500 mg for certain at-risk populations), consume less than 300 mg per day of dietary cholesterol, limit foods containing synthetic sources of trans fats, and reduce the intake of calories from solid fats and added sugars. 

Although the 2010 Dietary Guidelines are intended to help form federal nutrition policy and provide guidance to be used by nutrition educators and health professionals, in effect, they are a signal to food manufacturers regarding the type and quality of food that consumers, whether currently health-conscious or not, may well be seeking. 

Recent federal and state government efforts to address the obesity epidemic have created fertile ground for healthy food product innovation.  For example, the Healthy, Hunger-Free Kids Act of 2010 authorizes USDA to set nutritional standards for foods sold in schools, including vending machines, lunch lines, and school stores.  Combating the problem from a different angle, Alabama’s State Employees’ Health Insurance plan provides a financial incentive to workers taking steps to improve their blood pressure, cholesterol, glucose, or body mass index readings, if their measurements are deemed to put them “at risk.”  Employees can receive a health insurance discount if, for example, they participate in a wellness management program.

Creating palatable healthful foods that meet the criteria of the guidelines undoubtedly presents some food design challenges:  American consumers are known for their love of sugar-laden beverages and high-fat and high-sodium meals.  Nevertheless, consumer education about nutrition, combined with health insurance and other incentives to obtain (and maintain) a healthy weight, seems likely to lead more consumers to seek the types of foods described in the new dietary guidelines.  Food manufacturers that can make nutritious foods without sacrificing taste should benefit.

By Peter M. Jaensch –

In what appears to be yet another example of a consumer fraud class action that cites alleged  violations of the FDC Act and its implementing regulations, on February 1, 2011, Athena Hohenberg filed a class action lawsuit in U.S. District Court for the Southern District of California against Ferrero U.S.A., Inc. (“Ferrero”), the manufacturer of the popular hazelnut and cocoa spread, Nutella®, alleging violations of California law based upon Ferrero’s allegedly false and misleading labeling and advertising of Nutella® as part of a “balanced breakfast.”  The Complaint also cites Ferrero’s use of photographs depicting mothers feeding Nutella® to their healthy-looking children, and statements on the label of the product that Nutella® is “‘[a]n example of a tasty yet balanced breakfast’ in association with a picture showing fresh fruits, whole wheat bread, and orange juice” as examples of false, deceptive, and misleading advertising of Nutella® in light of plaintiff’s allegation that Nutella® “contains about 70% saturated fat and processed sugar by weight” and “the same amount of saturated fat as a Twix Ice Cream bar.” Consequently, plaintiff claims, health-conscious consumers were duped into paying more for Nutella® than they would have been willing to pay had they known its true nutritional value.

In addition to unspecified damages, attorney’s fees, and punitives, Ms. Hohenberg seeks an order from the Court “compelling Ferrero to (1) cease marketing its products using the misleading tactics complained of [in the Complaint], (2) conduct a corrective advertising campaign, (3) restore the amounts by which Ferrero was unjustly enriched, and (4) destroy all misleading and deceptive materials and products.”

By the way, you can have your Nutella® and your ice cream too. CAUTION: Choco-Hazelnut Ice Cream is not a salad.